Oropouche virus transmission to unborn child confirmed

The first confirmed case of vertical transmission of Oropouche virus (OROV) has been reported by 23 researchers from eight distinct institutions in Brazil.

OROV, a zoonotic arbovirus, was first isolated from the blood of a charcoal worker with a high fever in 1955 on the Caribbean island of Trinidad. Outbreaks have typically occurred south of the Amazon, isolated within Amazonian villages.

In 2024, OROV infections were detected in previously non-endemic areas across all five Brazilian regions. These expansions into previously unaffected regions involve new virus variants emerging from genetic reassortment.

In a letter to the editor titled "A Case of Vertical Transmission of Oropouche Virus in Brazil," published October 30, 2024, in the New England Journal of Medicine, researchers report on a case from Ceará, a state historically free from OROV, finding its first infection case through active laboratory surveillance.

Subsequent investigations identified 171 cases, predominantly in the rural valleys of the Baturité Massif. Agricultural landscapes in this region favor the Culicoides paraensis midge, a small biting fly sometimes referred to as "no-see-ums" due to their tiny size. Culicoides is the primary vector for OROV transmission to humans.

A notable case involved a 40-year-old pregnant woman at 30 weeks gestation who developed fever, chills, muscle aches, and severe headache. Routine prenatal care had previously identified gestational diabetes, managed with metformin, and four routine obstetric ultrasounds.

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On July 27, medical evaluation revealed light vaginal bleeding and dark discharge, with ultrasonography indicating fetal macrosomia.

By August 5, continued symptoms and decreased fetal movements led to the confirmation of fetal demise.

Molecular diagnostics confirmed acute OROV infection, ruling out dengue, Zika, chikungunya, and Mayaro viruses. Minimal invasive tissue sampling of the stillborn infant revealed OROV RNA in multiple fetal tissues, establishing vertical transmission.

Phylogenetic analysis using maximum-likelihood inference positioned the virus within the OROVBR-2019-2024 lineage, consistent with strains from the ongoing outbreak. These findings link the stillbirth directly to the current OROV spread in Brazil, highlighting the virus's potential risks during pregnancy.

The report should sound the alarm for health care providers to consider OROV infection in pregnant women presenting with fever and related symptoms in endemic or emerging regions.

 Carlos Garcia Filho et al, A Case of Vertical Transmission of Oropouche Virus in Brazil, New England Journal of Medicine (2024). DOI: 10.1056/NEJMc2412812

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Redefining net zero will not stop global warming, scientists say

This is really absurd. Governments and countries are trying to evade climate goals to stop global warming. 

In a study, led by the University of Oxford's Department of Physics and published 18 November in Nature, an international group of authors who developed the science behind net zero demonstrate that relying on 'natural carbon sinks' like forests and oceans to offset ongoing CO2 emissions from fossil fuel use will not actually stop global warming.

The science of net zero, developed over 15 years ago, does not include these natural carbon sinks in the definition of net human-induced CO₂ emissions.

Natural sinks play a vital role in moderating the impact of current emissions and draw down atmospheric CO2 concentrations after the date of net zero, stabilizing global temperatures. Yet governments and corporations are increasingly turning to them to offset emissions, rather than reducing fossil fuel use or developing more permanent CO2 disposal options.

Emissions accounting rules encourage this by creating an apparent equivalence between fossil fuel emissions and drawdown of CO₂ by some natural carbon sinks, meaning a country could appear to have 'achieved net zero' while still contributing to ongoing warming.

The authors call on governments and corporations to clarify how much they are counting on natural carbon sinks to meet their climate goals, as well as recognizing the need for "Geological Net Zero."

Geological Net Zero means balancing flows of carbon into and out of the solid Earth, with one ton of CO₂ committed to geological storage for every ton still generated by any continued fossil fuel use. Given the cost and challenges of permanent geological CO₂ storage, achieving Geological Net Zero will require a substantial reduction in fossil fuel use.

The authors stress the importance of protecting and maintaining natural carbon sinks while accepting that doing so cannot compensate for ongoing fossil fuel use. Total historical CO₂ emissions determine how much a country or company has contributed to the global need for ongoing natural carbon sinks.

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We are already counting on forests and oceans to mop up our past emissions, most of which came from burning stuff we dug out of the ground. We can't expect them to compensate for future emissions as well. By mid-century, any carbon that still comes out of the ground will have to go back down, to permanent storage. That's Geological Net Zero.
Countries report both emissions and removals, but using all removals in climate targets is a recipe for continued warming. Natural carbon sinks currently clean up around half our annual emissions for free, but this ecosystem service must be kept separate from the fossil emissions driving climate change. Relabeling things will not stop global warming, say the scientists.
They stress that: It is a common assumption that removing carbon from the atmosphere to offset burning of fossil fuels is as effective as not burning fossil fuels in the first place. It is not.
Offsetting continued fossil fuel use with carbon removal will not be effective if the removal is already being counted on as part of the natural carbon cycle and if the carbon is not permanently stored. Unless we can increase transparency in national Greenhouse gas reporting and target setting, offsets will become part of the problem instead of part of the solution.
Land is limited, we rely on it for food, nature, biodiversity, leisure, water storage, and so on. It cannot offset more than a portion of fossil emissions even now, probably less in future, with worsening pressures on the biosphere such as population increase, fires, and drought.

"Giving carbon credits for natural processes that are happening anyway undermines trust in the whole idea of offsetting. We have to urgently protect natural carbon sinks, but there are more scientifically credible and equitable ways of doing this than relying on carbon offset markets."
Is anybody listening?

Myles Allen, Geological Net Zero and the need for disaggregated accounting for carbon sinks, Nature (2024). DOI: 10.1038/s41586-024-08326-8. www.nature.com/articles/s41586-024-08326-8

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Extreme heat weakens land's power to absorb carbon, analysis finds

A new European Space Agency-backed study shows that the extreme heat waves of 2023, which fueled huge wildfires and severe droughts, also undermined the land's capacity to soak up atmospheric carbon. This diminished carbon uptake drove atmospheric carbon dioxide levels to new highs, intensifying concerns about accelerating climate change.

Measurements from Hawaii's Mauna Loa Observatory showed that atmospheric carbon concentrations surged by 86% in 2023 compared to the previous year, marking a record high since tracking began in 1958.

Despite this sharp increase, fossil fuel emissions only rose by about 0.6%, suggesting that other factors, such as weakened carbon absorption by natural ecosystems, may have driven the spike.

An international team of scientists analyzed global vegetation models and satellite data to investigate the underlying causes and deliver an expedited carbon budget report for 2023.

Typically, land absorbs roughly one-third of human-generated carbon dioxide emissions. However, the team's research published in National Science Review reveals that in 2023, this capacity fell to just one-fifth of its usual level, marking the weakest land carbon sink performance in two decades.

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Widespread wildfires across Canada and droughts in the Amazon in 2023 released about the same amount of carbon to the atmosphere as North America's total fossil fuel emissions, underscoring the severe impact of climate change on natural ecosystems.

The Amazon—one of the world's most crucial carbon sinks—is showing signs of long-term strain, with some regions shifting from absorbing carbon to becoming net sources of carbon emissions.

The researchers suggest that the declining capacity of Earth's land ecosystems to absorb carbon dioxide may indicate that these natural carbon sinks are nearing their limits and no longer able to provide the mitigation service they have historically offered by absorbing half of human-induced carbon dioxide emissions.
Consequently, achieving safe global warming limits will require even more ambitious emission reductions than previously anticipated, the scientists say.
The study also highlights that current climate models might be underestimating the rapid pace and impact of extreme events, such as droughts and fires, on the degradation of these crucial carbon reservoirs.

Piyu Ke et al, Low latency carbon budget analysis reveals a large decline of the land carbon sink in 2023, National Science Review (2024). DOI: 10.1093/nsr/nwae367

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Magenta aurora over Japan

Why May 2024's aurora appeared a magenta color over Japan?

Around the world, the historic geomagnetic superstorm of late spring 2024 inspired millions of non-scientists around the world—many armed with highly sensitive smartphone cameras—to take a fantastic, unprecedented number of images of the aurora it produced.

In Japan, this widespread popular uptake of what is now quite advanced imaging technology (even if it is kept in everyone's pocket) proved to be a tremendous boon for atmospheric physicists and other scientists specializing in "space weather." It allowed them to discover why the Northern Lights over Japan appeared as a mysterious magenta color this time instead of the typical red that is observed when aurorae are visible over that country.

In early May this year, one of the most extreme geomagnetic storms in the history of recording such events hit the Earth's atmosphere. This great "storm" in space, composed of ionized particles, is what produces the aurora borealis, or Northern Lights, in the northern hemisphere and the aurora australis, or Southern Lights, in the southern hemisphere.

This time, however, the storm was so strong—the ninth most severe storm in the 110-year history of Japan's Kakioka Magnetic Observatory, one of the oldest geomagnetic stations in the world—that the polar lights could be photographed at much lower latitudes than normal.
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In Japan, space weather researchers took advantage of ordinary people taking pictures of the aurora with their smartphones to organize one of the densest citizen science observation efforts anywhere, despite being a low-latitude country where the aurora was somewhat fainter than in places like Canada or northern Europe.

The different colors of an aurora come from the emission of light from different atoms and molecules in the atmosphere when they are bombarded by the particles from space. The dramatic green hue seen in many photographs of the polar lights comes from atomic oxygen (single atoms of oxygen rather than molecular oxygen, or two oxygen atoms bound together) at the lower altitudes within the atmosphere that are visible to people. (The human eye is also just very sensitive to this color). At even lower altitudes, where atomic oxygen is less common, blue is more visible, and this comes from the greater presence of nitrogen.

At the very highest altitudes in the atmosphere, however, there is a lower concentration of atoms of any kind. The fewer collisions there result in a perception by humans of the excited atomic oxygen atoms as the color red. This is why the upper parts of the aurora curtains can appear as green fading into a scarlet hue.
At low latitudes, as in Japan, normally there is no green at all, only red because only the upper part of the aurora can be seen above the horizon.

"Yet this time, weirdly, the images revealed a very clear and dominant magenta hue to the aurora 'curtains' over Japan, not red.
To solve the mystery, the researchers quickly took to social media to encourage people to observe and report their sightings of the auroras, as well as to input data into a questionnaire asking about observation locations, time, elevation angles and other details, allowing researchers to analyze the auroras' characteristics in unprecedented detail.
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The effort resulted in an impressive 775 grassroots submissions, which the researchers then combined with satellite observations and advanced modeling techniques to explore the conditions that had led to the magenta aurora.

The elevation data from these citizen scientists proved to be particularly useful. The researchers used elevation angles to calculate the position of the aurora over time, and found that it was often a surprisingly high altitude of roughly 1,000 km above sea level—which should thus drive a red appearance. But on top of this, the time and season of year meant the atmosphere was more "preheated" ahead of the aurora, in turn driving an upwelling of ionized molecular nitrogen—what is usually responsible for a blue hue.
"Blue plus red makes us see magenta.
And the magenta was made all the more visible and vibrant by the sheer volume of solar activity, even though, ironically, the preheating would also have worked to reduce the peak brightness of the aurora."
Better understanding of magnetic storms goes beyond explaining why humans see the pretty colors of aurorae; these storms can have profound, negative impacts on satellite operations, GPS systems, power grids and even the safety of passengers and crews aboard high-altitude flights.

 Ryuho Kataoka et al, Extended magenta aurora as revealed by citizen science, Scientific Reports (2024). DOI: 10.1038/s41598-024-75184-9

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Confinement may affect how we smell and feel about food

New research  found confined and isolating environments changed the way people smelled and responded emotionally to certain food aromas.

The team in this study compared 44 people's emotional responses and perception of eight food aromas in two environmental scenarios: sitting in reclined chairs that mimic astronauts' posture in microgravity; and then in the confined setting of the International Space Station (ISS), which was simulated for participants with virtual reality goggles.
The aromas the team tested on participants were vanilla, almond, lemon, lemon myrtle, eucalyptus, peppermint, vinegar and lemongrass.

The research, published in Food Research International, builds on previous work by the team and aims to help explain why astronauts report meals taste different in space and struggle to eat their normal nutritional intake over long missions, which has been reported in the news recently.

The study has broader implications for further research to improve the diets of isolated people, including nursing home residents, by personalizing aromas to enhance the flavor of their food.
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Lemongrass consists of a more floral and earthy aroma, while the other aromas are pungent, spicy or sweet. This difference in profile may explain why lemongrass seemed less intense in the VR setting compared to the microgravity posture.
In an Earth-like setting, eating was often social, but eating in space on long missions can feel quite different.
Pilot studies [published open-access in the journal Science Talks] show that spending 10 minutes in VR can induce feelings of confinement, highlighting VR's effectiveness over other methods such as immersive screens.

"Results indicate that a remote, confined environment such as the ISS and a significant variation in personal sensitivities influence aroma perception, making certain foods smell strange.
Space studies often emphasized microgravity as the main contributing factor to food's different taste, but the team's findings underscored the impact of confined and isolated environments.
This research opens possibilities for personalized meal plans for astronauts and individuals living alone on Earth, showcasing VR's potential to explore variations in eating when stressed.
In the VR setting, participants reporting positive emotions perceived stronger aromas.This link between stress and vinegar may help explain why astronauts like to eat certain foods in microgravity that they don't normally enjoy on Earth.

Food odour perception and affective response in virtual spacecraft and microgravity body posture (1-G) – potential ground-based simulations, Food Research International (2024).

Julia Low et al, Development of a virtual reality spacecraft environment as a ground-based analog for collecting space food sensory data ('Food in Space'), Science Talks (2024). DOI: 10.1016/j.sctalk.2024.100391

Alicia Tran et al, Exploring fundamentals of immersive environment setups on food sensory perception in space contexts, Science Talks (2024). DOI: 10.1016/j.sctalk.2024.100403

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Scientists transform blood into regenerative materials, paving the way for personalized, 3D-printed implants

Scientists have created a new 'biocooperative' material based on blood, which has been shown to successfully repair bones, paving the way for personalized regenerative blood products that could be used as effective therapies to treat injury and disease.

Researchers have used peptide molecules that can guide key processes taking place during the natural healing of tissues to create living materials that enhance tissue regeneration. The research is published in Advanced Materials.

Most of our body tissues have evolved to regenerate ruptures or fractures with remarkable efficacy, as long as these are small in size. This healing process is highly complex. The initial stages rely on liquid blood forming the solid regenerative hematoma (RH), a rich and living microenvironment comprising key cells, macromolecules, and factors that orchestrate regeneration.
The team developed a self-assembling methodology where synthetic peptides are mixed with whole blood taken from the patient to create a material that harnesses key molecules, cells, and mechanisms of the natural healing process. In this way, it was possible to engineer regenerative materials capable of not only mimicking the natural RH, but also enhancing its structural and functional properties.
These materials can be easily assembled, manipulated, and even 3D printed while maintaining normal functions of the natural RH, such as normal platelet behavior, generation of growth factors, and recruitment of relevant cells important for healing. With this method, the team has shown the capacity to successfully repair bone in animal models using the animal's own blood.

Soraya Padilla‐Lopategui et al, Biocooperative Regenerative Materials by Harnessing Blood‐Clotting and Peptide Self‐Assembly, Advanced Materials (2024). DOI: 10.1002/adma.202407156

Scientists convert plastics into soaps and detergents

Researchers found  a way to convert certain plastics into soaps, detergents, lubricants, and other products.

  The process has two steps. It first involved using thermolysis, or breaking down a substance—in this case, plastic—by using heat. Plastic placed in a reactor built by the research team and heated to between 650 and 750 degrees Fahrenheit broke down into chemical compounds, leaving a mixture of oil, gas, and residual solids.

The key to this first step was breaking down the polypropylene and polyethylene molecules that make up plastic within a certain carbon range, and Liu and his team were able to accomplish this.

The residual solids left behind were minimal, and the gas could be captured and used as fuel. The oil, though, was the product of the most interest here.

They were also was able to functionalize, or change the chemistry, of the oil into molecules to be converted into soaps, detergents, lubricants, and other products.

These materials are stable. You could use them  to wash your hands and dishes. The researchers have used them to wash their lab glassware in the laboratory.

The process, which took less than a day, led to almost zero air pollution output, thus offering clues to a desperately needed solution to a global problem.

Nuwayo Eric Munyaneza et al, Chain-length-controllable upcycling of polyolefins to sulfate detergents, Nature Sustainability (2024). DOI: 10.1038/s41893-024-01464-x

Researchers uncover how blood pressure drugs harm kidneys

Commonly prescribed drugs used to treat high blood pressure have been shown to, over time, wreck the kidneys' ability to filter and purify blood. How does this happen?

Researchers found that the drugs essentially rewire the kidneys to do something other than the important work of filtering blood. The kidneys start producing more of a hormone called renin; nerve endings grow excessively; cells lining the kidneys' tiny blood vessels get too large; scars form and spread; and inflammation sets in, which "can take a terrible toll on the kidney.

The result, outlined in the researchers' paper in the journal Circulation Research, is a "silent but serious" vascular disease where the kidneys become zombie-like, changing into something unwanted and unwelcome while abandoning their critical duties.

Now that they know the cause, researchers say the next step is to figure out how to use the effective blood pressure drugs known as renin-angiotensin system inhibitors—often called RAS inhibitors—while stopping the kidney-damaging effects.

RAS inhibitors, which include the generics enalapril, lisinopril, ramipril and others, are commonly prescribed when a patient is first diagnosed with high BP.

The drugs work by relaxing blood vessels and allowing blood to flow more freely. The medicines are widely used and generally considered safe, researchers say, but are not without risk. Doctors have long warned patients that certain blood pressure medications could cause kidney damage, often first noticed as a reduction in the frequency of urination, swelling in the legs or feet, or seizures.

Now that scientists understand what is causing the kidney changes, they can look for ways to stop it.

These findings may open new avenues for the prevention of adverse effects when treating hypertension.

Manako Yamaguchi et al, Transformation of the Kidney into a Pathological Neuro-Immune-Endocrine Organ, Circulation Research (2024). DOI: 10.1161/CIRCRESAHA.124.325305

High exposure to everyday chemicals linked to asthma risk in children

A new study by researchers at Kumamoto University sheds light on a potential link between exposure to certain everyday chemicals during pregnancy and the development of asthma in children. The study analyzed data from over 3,500 mother-child pairs as part of the Japan Environment and Children's Study (JECS), a large-scale nationwide research project.

researchers measured 24 types of phenols in urine samples collected from pregnant women. They then tracked the health of their children until the age of four.

The study is published in the journal Environmental Pollution.

High levels of butylparaben, a chemical commonly used in personal care products like lotions and shampoos, during early pregnanacy were associated with a 1.54-fold increase in the odds of asthma development in children (Odds Ratio: 1.54).

Exposure to 4-nonylphenol, a chemical found in some cleaning products and plastics, showed a striking gender-specific effect. Boys born to mothers exposed to this chemical had 2.09 times higher odds of developing asthma, while no such association was observed in girls.

Phenols, including parabens and alkylphenols, are widely used in consumer products for their preservative and antimicrobial properties. While their use is considered safe in small amounts, their potential as endocrine disruptors raises concerns about long-term health effects, such as the recent increase in allergenic diseases such as asthma, particularly during sensitive periods like pregnancy.

The findings highlight the importance of understanding how everyday chemical exposures might contribute to respiratory and allergic conditions in children.

Shohei Kuraoka et al, Association of phenol exposure during pregnancy and asthma development in children: The Japan Environment and Children's study, Environmental Pollution (2024). DOI: 10.1016/j.envpol.2024.124801

By exerting 'crowd control' over mouse cells, scientists make progress towards engineering tissues
Genes aren't the sole driver instructing cells to build multicellular structures, tissues, and organs. In a paper published in Nature Communications, scientists characterize the influence of another important developmental driver: cell density, or how loosely or tightly cells are packed into a given space.

In both computational models and laboratory experiments, the team of scientists used cell density as an effective tool for controlling how mouse cells pattern themselves into complex structures.

This paper represents progress towards their big picture goal of engineering synthetic tissues. Synthetic tissues could have endless medical applications, ranging from testing potential drugs or therapies to providing grafts or transplants for patients.

The study used two types of mouse cells—connective tissue cells and stem cells—engineered to carry a synthetic cellular communication system or "genetic circuit. This circuit is based on something they developed called "synNotch," which is a protein that scientists genetically engineer into a cell to serve as a "sensor."

Located on a cell's surface, this protein-based sensor recognizes an external signal that triggers the cell to respond—usually by turning on a user-defined gene.

For this particular series of experiments, the scientists used synNotch to turn on a circuit that includes green fluorescence and a way to propagate the signal further—although it could be used to turn on any gene. The fluorescence made it easy to observe cells as they formed patterns. For example, in a field of cells, scientists could create a pattern of green fluorescent rings emanating from a central point.

While conducting these experiments, the scientists noticed that genetically identical cells did not always produce the same patterns.

So that was puzzling at the beginning. When the researchers looked at it more carefully, they started seeing that there was a gradient of cell density that seemed to correlate with differences in patterning.

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Above a certain cell density, synNotch exerted a weaker effect and didn't produce the same patterns. Further complicating matters, cell density constantly shifted as cells proliferated at ever changing rates—interacting in complex ways with the synNotch genetic circuit.

The scientists then built a computational model that could predict and clarify this complex and dynamic cell behaviour. It helped guide them to think about how the cell density, proliferation rate, signaling, and all these different things conspire.

Guided by the computational model, the scientists were able to use cell density to generate a variety of predictable fluorescent patterns that developed over specific timeframes.

To understand how cell density was exerting these effects, the scientists conducted a series of experiments that yielded a surprising discovery. Greater cell density induces stress that leads to a quicker breakdown of not only synNotch in particular, but also cell surface sensors in general.

This means that cell density is a broadly applicable tool for guiding both engineered and naturally occurring cells to build a vast array of structures, tissues, and organs.

Nature has relied on cell density in conjunction with genetic circuits to generate the remarkable diversity of multicellular structures, tissues, and organs.

Now we can co-opt this same strategy to advance our efforts to build synthetic multicellular structures—and eventually tissues and organs—for regenerative medicine, say the scientists.

Nature Communications (2024). DOI: 10.1038/s41467-024-53078-8

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Research reveals even single-cell organisms exhibit habituation, a simple form of learning

Up until recently, habituation -- a simple form of learning -- was deemed the exclusive domain of complex organisms with brains and nervous systems, such as worms, insects, birds, and mammals. But a new study offers compelling evidence that even tiny single-cell creatures such as ciliates and amoebae, as well as the cells in our own bodies, could exhibit habituation akin to that seen in more complex organisms with brains.

A dog learns to sit on command, a person hears and eventually tunes out the hum of a washing machine while reading … The capacity to learn and adapt is central to evolution and, indeed, survival.

Habituation involves the lessening response to a stimulus after repeated exposure. Think of the need for a third espresso to maintain the same level of concentration you once achieved with a single shot.

Up until recently, habituation -- a simple form of learning -- was deemed the exclusive domain of complex organisms with brains and nervous systems, such as worms, insects, birds, and mammals.

But a new study, published Nov. 19 in Current Biology, offers compelling evidence that even tiny single-cell creatures such as ciliates and amoebae, as well as the cells in our own bodies, could exhibit habituation akin to that seen in more complex organisms with brains.

This finding opens up an exciting new mystery for us: How do cells without brains manage something so complex?

The results add to a small but growing body of work on this subject. Earlier work led by Gunawardena found that a single-cell ciliate showed avoidance behavior, not unlike the actions observed in animals that encounter unpleasant stimuli.

Instead of studying cells in a lab dish, the scientists used advanced computer modeling to analyze how molecular networks inside ciliate and mammalian cells respond to different patterns of stimulation. They found four networks that exhibit hallmarks of habituation present in animal brains.

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These networks shared a common feature: Each molecular network had two forms of "memory" storage that captured information learned from the environment. One memory decayed much faster than the other -- a form of memory loss necessary for habituation, the researchers noted. This finding suggests that single cells process and remember information over different time spans.

Studying habituation in single cells could help propel understanding of how learning in general works, the researchers said. The findings also cast the humble single-cell creatures in a new, more tantalizing light: They are not merely molecular machines packed in microscopic bodies, but they are also agents that can learn.

Practical applications of this work:

One daring idea would be to apply the concept of habituation to the relationship between cancer and immunity.

Tumors are notoriously good evaders of immune surveillance because they trick immune cells into viewing them as innocent bystanders. In other words, the immune cells responsible for recognizing cancer may get somehow habituated to the presence of a cancer cell -- the immune cell gets used to the stimulus and no longer responds to it.

If we knew how these false perceptions get encoded in immune cells, we may be able to re-engineer them so that immune cells begin to perceive their environments correctly, the tumor becomes visible as malign, and they get to work.

Lina Eckert, Maria Sol Vidal-Saez, Ziyuan Zhao, Jordi Garcia-Ojalvo, Rosa Martinez-Corral, Jeremy Gunawardena. Biochemically plausible models of habituation for single-cell learning. Current Biology, 2024; DOI: 10.1016/j.cub.2024.10.041

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Astronauts found to process some tasks slower in space, but no signs of permanent cognitive decline

A stay in space exerts extreme pressures on the human body. Astronauts' bodies and brains are impacted by radiation, altered gravity, challenging working conditions, and sleep loss—all of which could compromise cognitive functioning. At the same time, they are required to perform complex tasks, and minor mistakes can have devastating consequences.

Working with 25 astronauts who spent an average of six months on the International Space Station (ISS), researchers  have examined changes in a wide range of cognitive performance domains. This dataset makes up the largest sample of cognitive performance data from professional astronauts published to date.

The research shows that there is no evidence of any significant cognitive impairment or neurodegenerative decline in astronauts spending six months on the ISS. Living and working in space was not associated with widespread cognitive impairment that would be suggestive of significant brain damage.

The results showed that responses to tasks assessing processing speed, working memory, and attention were slower than on Earth, but they were no less accurate. These changes, however, did not persist equally long.

Slowed performance on attention, for example, was only observed early during the mission, while slowed performance on processing speed did not return to baseline levels until after the mission ended and the crew were back on Earth.

Overall, astronauts' cognitive performance was stable, and the researchers did not find evidence that would suggest damage to the central nervous system during a six-month space mission.

Cognitive Performance in ISS Astronauts on 6-month Low Earth Orbit Missions, Frontiers in Physiology (2024). DOI: 10.3389/fphys.2024.1451269

'Flame-Throwing' Guitar Nebula

Ethiopian wolves seen feeding on nectar of red hot poker flowers

Strange things happen in nature!

New findings, published in the journal Ecology, describe a newly documented behavior of Ethiopian wolves (Canis simensis).

Researchers observed Ethiopian wolves foraging for the nectar of the Ethiopian red hot poker (Kniphofia foliosa) flower. Some individuals would visit as many as 30 blooms in a single trip, with multiple wolves from different packs exploiting this resource. There is also some evidence of social learning, with juveniles being brought to the flower fields along with adults.

In doing so, the wolves' muzzles become covered in pollen, which they could potentially transfer from flower to flower as they feed. This novel behavior is perhaps the first known plant-pollinator interaction involving a large predator, as well as the only large meat-eating predator ever to be observed feeding on nectar.

Sandra Lai et al, Canids as pollinators? Nectar foraging by Ethiopian wolves may contribute to the pollination of Kniphofia foliosa, Ecology (2024). DOI: 10.1002/ecy.4470

Scientists discover the molecular composition of potentially deadly venomous fish

New research in FEBS Open Bio reveals insights into the venom of two of the most venomous fish species on Earth: the estuarine stonefish (Synanceia horrida) and the reef stonefish (Synanceia verrucosa), which are typically found in the warm and shallow regions of the Indo-Pacific region, the Persian Gulf, and the Red Sea.

Through multiple analytical techniques, investigators discovered the presence of three neurotransmitters new to stonefish venom, namely gamma-aminobutyric acid (GABA), choline, and 0-acetylcholine.

Although these molecules have been previously found in venoms from other species, such as hornets and spiders, this is the first report of a fish venom that contains GABA, which is capable of modulating cardiovascular function with a range of effects including increased heart rate and low blood pressure.

Characterization of the specific composition of each of these fish species' venom not only provides us with a better understanding of envenomation mechanisms, which are needed for the development of targeted treatments against venom effects, but may also aid in the exploration and development of venom-derived compounds in drug discovery.

Silvia Luiza Saggiomo et al, Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp., FEBS Open Bio (2024). DOI: 10.1002/2211-5463.13926

Weight-loss drug found to shrink heart muscle in mice and human cells

Trendy weight-loss drugs making headlines for shrinking waistlines may also be shrinking the human heart and other muscles, according to a new  study in JACC: Basic to Translational Science. The authors say the research should serve as a "cautionary tale" about possible long-term health effects of these drugs.

Researchers set out to study why a reported side-effect of the leading weight-loss drug Ozempic is the loss of skeletal muscle.

Ozempic, known medically as semaglutide, was originally designed to help adult patients with type 2 diabetes control their blood sugar. However, this drug—and a host of others in this class of medication—are also being touted for their effectiveness as an anti-obesity medication.

Using mice for the study, the researchers found that heart muscle also decreased in both obese and lean mice. The systemic effect observed in mice was then confirmed in cultured human heart cells.

 Matthew D. Martens et al, Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice, JACC: Basic to Translational Science (2024). DOI: 10.1016/j.jacbts.2024.07.006

Females sleep less and awaken more frequently than males, which may have broad implications for medical research

Females sleep less, wake up more often and get less restorative sleep than males, according to a new animal study by researchers.

The findings, published in the journal Scientific Reports, shed new light on what may underlie sleep differences in men and women and could have broad implications for biomedical research, which for decades has focused primarily on males.

In humans, men and women exhibit distinct sleep patterns, often attributed to lifestyle factors and caregiving roles.  However, these new results suggest that biological factors  may play a more substantial role in driving these sleep differences than previously recognized.

Sleep research has exploded in recent years, with thousands of animal studies exploring how insufficient sleep impacts risk of diseases like diabetes, obesity, Alzheimer's and immune disorders—and how such diseases impact sleep.

But many of those results may have been skewed due to a lack of female representation, the study suggests.

The question the female researchers now ask is: Are we creating too much stress for ourselves because we don't sleep as much as our husband or partner and think our sleep is poor when actually that is a normal sleep profile for ourselves?

The authors hope their findings inspire more research into underlying biological differences. More importantly, they hope the study prompts scientists to re-evaluate how they do research and interpret the results.

Grant S. Mannino et al, The importance of including both sexes in preclinical sleep studies and analyses, Scientific Reports (2024). DOI: 10.1038/s41598-024-70996-1

Healthy women have cells that resemble breast cancer, study finds

A new study from cancer researchers   finds that, in healthy women, some breast cells that otherwise appear normal may contain chromosome abnormalities typically associated with invasive breast cancer. The findings question conventional thinking on the genetic origins of breast cancer, which could influence early cancer detection methods.

The study, published recently in Nature, discovered that at least 3% of normal cells from breast tissue in 49 healthy women contain a gain or loss of chromosomes, a condition known as aneuploidy, and that they expand and accumulate with age. This poses questions for our understanding of "normal" tissues, according to principal investigator of this research.

As researchers continue to develop earlier detection methods using molecular diagnostics along with ductal carcinoma in situ (DCIS) and biopsies, these findings pose a challenge and highlight the potential risk of identifying false positives, as the cells can mistakenly be confused with invasive breast cancer.

A cancer researcher or oncologist seeing the genomic picture of these normal breast tissue cells would classify them as invasive breast cancer.

"We've always been taught that normal cells have 23 pairs of chromosomes, but that appears to be inaccurate because every healthy woman that we analyzed in our study had irregularities, bringing up the very provocative question about when cancer actually occurs", say the researchers.

The study builds upon their previous work on the Human Breast Cell Atlas, which profiled over 714,000 cells to generate a comprehensive genetic map of normal breast tissue at the cellular level.

 Yiyun Lin et al, Normal breast tissues harbour rare populations of aneuploid epithelial cells, Nature (2024). DOI: 10.1038/s41586-024-08129-x

This Strange Crystal Has Two Melting Points

In 1896, German chemist Emil Fischer noted something very strange about a molecule named acetaldehyde phenylhydrazone. Identical batches of the crystalline compound appeared to have wildly different melting points.

Some batches, he found, melted at temperatures of around 65 degrees Celsius (149 Fahrenheit). Others at 100 degrees Celsius. It was, in a word, utterly bizarre. No other substance was known to behave this way. Nor should it.

According to the laws of thermodynamics that describe the way the physical world behaves, such a result should be impossible.

More than 120 years after Fischer's original discovery, in 2019, an international team of researchers led by chemist Terry Threfall of the University of Southampton in the UK finally found and published the answer. Fischer (who went on to win a 1902 Nobel prize for other work, so he was clearly no quack) had observed something real; but not, as it would turn out, anything that would break thermodynamics.

The culprit? An absolutely miniscule contamination, so small that it is all but undetectable. When acetaldehyde phenylhydrazone melts, it becomes one of two liquids, based on whether the compound has been exposed to a base or an acid. The former appears at the higher melting point; and the latter at the lower.

The observation of such behavior will be exceedingly rare because it depends on the molecules in the crystal and in the liquid having different geometries, which is unusual. Furthermore, it depends also on the conversion by acid being both possible and rapid.

Part 1

The compound is made by dissolving solid acetaldehyde and adding both liquid phenylhydrazine and aqueous ethanol, and chilling until the mixture freezes and forms solid crystals. To then discover the melting point of the newly formed acetaldehyde phenylhydrazone, you have to re-melt it.

This is where the problems emerged. To understand why acetaldehyde phenylhydrazone melts at two distinct temperatures, the researchers first investigated its solid form. But the most cutting edge probes failed to turn up an answer.

All analyses, performed by Threlfall's team and other recent efforts, failed to find a single difference between acetaldehyde phenylhydrazone samples that melted at the lower temperature, and samples that melted at the higher. These techniques included X-ray diffraction, nuclear magnetic resonance, and IR spectroscopy. As far as scientists could tell, the crystals were identical.
The next step was to investigate the liquid the crystals became after melting.

And there, the researchers got a result. There was a subtle, and temporary, but distinct difference. Although the compounds had the same molecular formula, the structure of the initial melt was slightly different, depending on the temperature.

The compound contains a methyl group that is able to have two distinct configurations, known as the Z isomer and the E isomer.

In its solid phase, the material almost exclusively consists of the Z isomer.

The most stable liquid phase is a mix of about one-third Z isomer to two-thirds E isomer. The lower of the two melting points immediately produces the Z and E mix, while the higher melting point is entirely Z, before switching to part E.
Part 2

A clue was given in a 1905 paper, which pointed out that acetaldehyde phenylhydrazone was extremely sensitive to acid. Threlfall and his team tried exposing their samples to vapors of acid and ammonia. And they found that exposure to just a tiny bit of one or the other could reliably influence the compound's melting point. The acid acts as a catalyst to speed the shift from the Z to E isomer, lowering the melting point in the process.
If an element or compound can exist in two or more distinct crystalline forms, then each form will have different Gibbs energies and melt at its own distinct temperature.
In this case, the molecules of the crystal are in the cis geometry – of groups pointing towards each other – and melt to an identical geometry in the absence of acid at 100 degrees Celsius. However, in the presence of even a trace of acid, the molecules convert on melting to the trans geometry of groups pointing away from each other. This liquid has a smaller Gibbs energy and is more stable, so the melting point becomes 65 degrees Celsius."

It's similar to the effect salt has on water: adding salt to a pot of water raises the freezing and boiling points. Where it takes a lot of salt to invoke a significant change to water's phase transitions, it takes so little acid to alter acetaldehyde phenylhydrazone that it took more than a century – and Threlfall and his colleagues a decade – to figure it out.

This research is a real testament to human curiosity and tenacity. And it gives us hope for the future. How many more mysteries will be solved in the years stretching into a glittering future of discovery?

https://pubs.acs.org/doi/10.1021/acs.cgd.8b01459

Part 3

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Cadavers could be bone-marrow donors
A new technique for collecting bone-marrow stem cells from a cadaver’s spinal column could provide transplants for people with blood cancers. A company called Ossium Health is creating a bank of cryopreserved marrow from organ donors with diverse genetic backgrounds. Unlike solid organ donors, a bone-marrow donor must be a very close genetic match to the recipient. This presents a particular challenge when trying to find donors for people from racial minority groups, who are underrepresented in donor registries. The cadaver bank could widen the potential donor pool, although it is still unclear whether the freezing process could damage the stem cells.

https://www.wired.com/story/stem-cell-donation-deceased-ossium-bone...

Neanderthal adhesive manufacturing site found in Gibraltar cave

Cut into a Gibraltar cliff face overlooking the Alboran Sea, a cave opening leads back in time to one of the earliest manufacturing sites on the planet—a Neanderthal-built tar distillation oven hidden for 65,000 years.

Researchers have discovered a complex Neanderthal hearth structure in Vanguard Cave. Middle Paleolithic stone artifacts and residues suggest Neanderthals produced tar from rockrose plants (Cistaceae) here, showing off their advanced fire management and technological capabilities.

Neanderthals used fire for warmth, light, cooking, landscape clearing, and extracting adhesive tar from specific plants and trees. Evidence of their use of fire in tar extraction is based on the composition of the tar residues left on tools.
Tar was used as an adhesive for hafting stone tools to wooden handles, representing a significant advancement in tool-making, predating current modern human tar adhesive use by more than 100,000 years.

While the techniques Neanderthals used to extract tar have been previously back-engineered to suggest the use of underground fire pits, direct evidence of these pits has been missing from the record.

In the current study, "A Neanderthal's specialized burning structure compatible with tar obtention," published in Quaternary Science Reviews, researchers analyzed a hearth pit structure in Vanguard Cave, employing geochemical, mineralogical, palynological and micromorphological methods.

They identified a central fire pit with two opposite-sided trenches, revealing a crust of altered rocks and sediment due to prolonged fire use. This structure aligns with theoretical models requiring specialized heating installations for tar production under low-oxygen conditions.

Part 1

Organic geochemical analysis revealed the presence of levoglucosan and significant amounts of retene in the structure's matrix, compounds associated with the combustion of resinous plant materials. Lipid analysis showed straight-chain n-alkanes of odd carbon numbers and n-alkanols of even carbon numbers, biomarkers indicative of fresh leaf wax from plants like rockrose.

Charcoal analysis uncovered partially vitrified remains of Cistaceae, or rockrose family plants, suggesting incomplete combustion under controlled conditions. Less than 10% of the charcoal was from conifer wood.

Palynological examination indicated the presence of abundant pollen grains within the structure, whereas surrounding sediments were free of pollen. This suggests the deliberate introduction of plant materials into the hearth by Neanderthals.

Micromorphological analysis showed no evidence of clay heating above 500°C, indicating that the structure was used for controlled low-temperature processes compatible with tar production.

Carbonate rocks within the structure appear placed intentionally, likely employed to maintain a seal composed of guano and sand. This seal would create a low-oxygen environment essential for effective tar distillation.

To test their hypothesis, the team conducted experimental archaeology by building a similar structure and using it to heat rockrose leaves under low-oxygen conditions. The experiment successfully produced tar sufficient to haft stone spearheads, using only tools and materials available to Neanderthals in the area.
Findings show Neanderthals organized complex fire-related activities by constructing specialized hearths for tar extraction. This confirms a level of cognitive complexity and cultural development previously expected based on their use of manufactured materials.

Juan Ochando et al, A Neanderthal's specialised burning structure compatible with tar obtention, Quaternary Science Reviews (2024). DOI: 10.1016/j.quascirev.2024.109025

Part 2

Study reveals RNA's unknown role in DNA damage repair

A multi-institutional team of researchers has discovered a previously unknown role for RNA. 

RNA molecules are best known as protein production messengers. They carry genetic instructions from DNA to ribosomes—the factories inside cells that turn amino acids into the proteins necessary for many cell functions. But this study found that RNA can also help cells repair a severe form of DNA damage called a double-strand break, or DSB.

A DSB means both strands of the DNA helix have been severed. Cells have the tools to make some repairs, but a DSB is significant damage—and if not properly fixed can lead to mutations, cell death, or cancer. (Interestingly, cancer treatments, like chemotherapy and radiation, can also cause DSBs.)

When a DSB happens in DNA, it's like a load-bearing beam in a building breaking. A careful, precise repair is needed to ensure the building's—or the DNA's—stability. The pieces must be rejoined accurately to prevent further damage or mutation. Repairing a damaged building requires having a reliable foreman on the job site. A DSB requires something very similar.

A key mechanism the researchers identified is that RNA can help position and hold the broken DNA ends in place, facilitating the repair process.

Specifically, they found that RNA molecules and the broken section of DNA can match up like puzzle pieces. When RNA has this kind of complementarity with the DNA break site, it acts as a scaffold, or a guide, beyond its traditional coding function, showing the cellular machinery where to make repairs. Over millennia, cells have evolved complex mechanisms to fix DSB, each of them functioning like different tools from the same toolbox.

This research work showed that RNA can influence which tools are used, depending on its complementarity to the broken DNA strands. This means that in addition to being the important protein production messenger, RNA acts as both a foreman and laborer when it comes to DNA repair.

A deeper understanding of RNA's role in DNA repair could lead to new strategies for strengthening repair mechanisms in healthy cells, potentially reducing the harmful effects of treatments like chemotherapy and radiation.

 Youngkyu Jeon et al, RNA-mediated double-strand break repair by end-joining mechanisms, Nature Communications (2024). DOI: 10.1038/s41467-024-51457-9

Survey shows millions of people hurt by others' drinking, drug use

The risks of alcohol and other drug consumption to the user are well known, but many Americans—nearly 160 million—say they've been harmed by someone else's substance use, according to a new study in the Journal of Studies on Alcohol and Drugs.

In a national survey of U.S. adults, researchers found that 34% said they'd ever suffered "secondhand harm" from someone else's alcohol use—ranging from marriage and family problems to financial fall-out to being assaulted or injured in a drunk-driving accident. Meanwhile, 14% said they'd been harmed by someone else's use of marijuana, opioids or other drugs.

In sheer numbers, that amounts to 113 million Americans who've suffered consequences from another person's drinking, and 46 million who've been hurt by others' drug use. What's more, there was plenty of "overlap" between those two groups: Of survey respondents reporting secondhand harms from alcohol, 30% said they'd also been impacted by other people's drug use. There are more harms than people think.

These habits affect families, relationships and communities.

It makes sense that risky drinking and drug use have far-reaching consequences, but it's only in recent years that research has delved into the secondhand harms of alcohol and drug use. 

 Rosen, E. M. et al.. Prevalence and correlates of alcohol and drug harms to others: Findings from the 2020 U.S. National Alcohol Survey. Journal of Studies on Alcohol and Drugs (2024). DOI: 10.15288/jsad.23-00387

History of endometriosis and fibroids linked to heightened risk of early death, study suggests

Women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature death, finds a large study published by The BMJ .

Endometriosis and uterine fibroids are common disorders among women of reproductive age. Endometriosis occurs when tissue similar to the lining of the womb grows in other places, such as the ovaries and fallopian tubes, while uterine fibroids are non-cancerous growths within or around the womb.

Growing evidence shows that both conditions are associated with a greater long term risk of chronic diseases, such as high blood pressure, heart disease, and some cancers, but their effect on risk of death before the age of 70 remains unclear.

To explore this further, researchers drew on information provided by 110,091 women taking part in the Nurses' Health Study II who were aged 25–42 years in 1989 and had no history of hysterectomy before endometriosis or fibroids diagnosis, cardiovascular diseases, or cancer.
Starting in 1993 and every two years thereafter, these women reported any diagnosis of endometriosis (confirmed by laparoscopy) and uterine fibroids (confirmed by ultrasound or hysterectomy).

Other potentially influential factors including age, ethnicity, reproductive history, HRT and oral contraceptive use, regular use of aspirin or anti-inflammatory drugs, and other health-related issues were also taken into account.

During 30 years of monitoring, 4,356 premature deaths were recorded, including 1,459 from cancer, 304 from cardiovascular diseases, and 90 from respiratory diseases.

Overall, the rate of all-cause premature death for women with and without confirmed endometriosis was 2.0 and 1.4 per 1,000 person years, respectively.

After taking account of age and other confounding factors such as weight (BMI), diet quality, physical activity, and smoking status, endometriosis was associated with a 31% higher risk of premature death, largely driven by deaths due to gynecological cancers.

Uterine fibroids were unrelated to all-cause premature death, but were associated with a greater risk of death due to gynecological cancers.
The researchers acknowledge that these are observational findings that relied on self-reports.
Nevertheless, this was a large study with regular follow-up over nearly three decades, which reduced potential recall errors.
As such, they conclude, "Our results suggest that women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature mortality extending beyond their reproductive lifespan."

"These conditions were also associated with an increased risk of death due to gynecological cancers. Endometriosis was also associated with a greater risk of non-cancer mortality. These findings highlight the importance for primary care providers to consider these gynecological disorders in their assessment of women's health."

 Yi-Xin Wang et al, Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study, BMJ (2024). DOI: 10.1136/bmj-2023-078797

Part 2

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2 million mph galaxy smash-up seen in unprecedented detail

A massive collision of galaxies sparked by one traveling at a scarcely-believable 2 million mph (3.2 million km/h) has been seen in unprecedented detail by one of Earth's most powerful telescopes.

The dramatic impact was observed in Stephan's Quintet, a nearby galaxy group made up of five galaxies first sighted almost 150 years ago.

It sparked an immensely powerful shock akin to a "sonic boom from a jet fighter"—the likes of which are among the most striking phenomena in the universe.

Stephan's Quintet represents "a galactic crossroad where past collisions between galaxies have left behind a complex field of debris", which has now been reawakened by the passage of the galaxy, NGC 7318b.

The collision was spotted by a team of scientists using the first observations from the new 20-million Euro (£16.7million) William Herschel Telescope Enhanced Area Velocity Explorer (WEAVE) wide-field spectrograph in La Palma, Spain.

The discovery of NGC 7318b smashing through Stephan's Quintet was observed by a team of more than 60 astronomers and has been published in Monthly Notices of the Royal Astronomical Society.

M I Arnaudova et al, WEAVE First Light Observations: Origin and Dynamics of the Shock Front in Stephan's Quintet, Monthly Notices of the Royal Astronomical Society (2024). DOI: 10.1093/mnras/stae2235

Standing at work can be detrimental to blood pressure, study suggests

Hmmm! Whole day sitting is not good. Right.

Now a Finnish study found that prolonged standing at work had a negative impact on the research participants' 24-hour blood pressure. In contrast, spending more time sitting at work was associated with better blood pressure.

The study, published in the journal Medicine & Science in Sports & Exercise, suggests that activity behavior during working hours may be more relevant to 24-hour blood pressure than recreational physical activity.

Regular exercise is important for controlling blood pressure. In particular, more vigorous, aerobic exercise is effective for lowering blood pressure, but everyday physical activity can also have a beneficial impact. Previous studies have shown that exercise in leisure time is more beneficial for the cardiovascular system than physical activity at work, which can even be detrimental to health.

In the Finnish Retirement and Aging study (FIREA) conducted at the University of Turku, the physical activity of municipal employees approaching retirement age was measured using thigh-worn accelerometers during working hours, leisure time, and days off. In addition, the research participants used a portable blood pressure monitor that automatically measured their blood pressure every 30 minutes for 24 hours.

The latest results confirm previous findings that physical activity at work can be harmful to the heart and circulatory system. In particular, prolonged standing can raise blood pressure as the body boosts circulation to the lower limbs by constricting blood vessels and increasing the pumping power of the heart.

A standing desk can provide a nice change from sitting at the office, but too much standing can be harmful. It's a good idea to take a break from standing during the work day, either by walking every half an hour or sitting for some parts of the day, the researchers recommend.

In addition, the results of the study suggest that sedentary work in itself is not necessarily harmful to BP. Instead, researchers stress the importance of recreational physical activity.

It is good to remember that being physically active at work is not enough on its own. Engaging in diverse physical exercise during leisure time helps to maintain fitness, making work-related strain more manageable. Similarly, employees with predominantly sedentary jobs should ensure that they get enough exercise during their leisure time.

Jooa Norha et al, Associations between Leisure and Work Time Activity Behavior and 24 H Ambulatory Blood Pressure among Aging Workers, Medicine & Science in Sports & Exercise (2024). DOI: 10.1249/MSS.0000000000003594

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Physicists Transformed a Quantum Computer Into a Time Crystal
For the first time, physicists have transformed a quantum processor into a state of matter that seems to defy physics, a breakthrough that could be a step toward making quantum computing more practical.
Quantum computers promise to broaden the kinds of algorithms that can be run quickly and practically, potentially speeding up research into many fields, from particle physics to pharmacology to meteorology.

Monumental progress has been made in developing the technology's foundations, but as the technology scales up, errors become a major obstacle.

By experimentally making a quantum computer behave like a robust form of time crystal, a team of physicists from China and the US hope to make the technology less prone to errors as it scales.

Time crystals are groups of particles that display repeating patterns. Where the patterns that make up regular crystals like diamond and quartz echo through 3D space, time crystals move periodically like a pendulum, tick-tocking through time.

What makes them unique is their ability to do this in absence or in contrast to a driving 'push'. Time crystals oscillate in their lowest energy state to their own rhythm, like a child kicking out in their swing in defiance of their parent's repetitive nudges.

https://www.nature.com/articles/s41467-024-53077-9

A Rare, Fatal Skin Disease Has Been Cured in Patients For The First Time
A rare and potentially fatal skin infection with nightmarish outcomes may soon have a cure.

The infection starts as a seemingly harmless rash, and before a person knows it, more than 30 percent of the skin on their body begins to blister and peel off in sheets, usually starting with the face and chest before progressing to the mouth, eyes, and genitals.
Infections, organ failure, and pneumonia can soon follow. In a third of all cases, the condition proves fatal. For those who survive, recovery can take months and usually requires similar treatment to burn victims.

The debilitating infection is an immune response to medication, called toxic epidermal necrolysis (TEN), and while it is thankfully very rare, impacting a million or two people worldwide every year, its onset is highly unpredictable.

TEN is linked with more than 200 medications, and it can impact all age groups and ethnicities, although it tends to be more common in females than males and is 100 times more prevalent in those with the human immunodeficiency virus ( HIV).
An international team of researchers now have cured seven patients with TEN or a slightly less severe version of the infection, known as Stevens–Johnson syndrome (SJS). None of the patients reported side effects.
All seven people treated with this therapy in their study experienced rapid improvement and a full recovery, in staggering results that have likely unlocked a cure for the condition.
One of those patients was a 59-year-old man who developed TEN across 35 percent of his body after beginning treatment for lung cancer. The patient had lost so much skin, his predicted mortality risk was nearly 60 percent.

Upon taking a novel immune inhibitor, however, his infection stopped progressing. After 16 days, he was almost fully healed.
The class of drugs, called JAK inhibitors (JAKi), seem to work by suppressing an overactive immune pathway.

Scientists discovered the importance of this signaling pathway using skin samples from patients with TEN, to see which individual cells were driving the deadly disease. Altogether, they identified six proteins involved in the JAK/STAT pathway that are upregulated in those with the skin infection.

The JAK/STAT pathway is the main driver of skin inflammation, damaged skin cells, and epidermal detachment.

Using rodent models of TEN, researchers found that one to three days after taking an oral JAK inhibitor, the skin infections had noticeably improved.
All seven patients responded well to the treatment and were discharged in good health, paving the way for a future clinical trial.

https://www.nature.com/articles/s41586-024-08061-0#Sec9

Oldest known alphabet unearthed in ancient Syrian city

What appears to be evidence of the oldest alphabetic writing in human history is etched onto finger-length, clay cylinders excavated from a tomb in Syria by a team of Johns Hopkins University researchers.

The writing, which is dated to around 2400 BCE, precedes other known alphabetic scripts by roughly 500 years, upending what archaeologists know about where alphabets came from, how they are shared across societies, and what that could mean for early urban civilizations.

At Umm-el Marra, the archaeologists uncovered tombs dating back to the Early Bronze Age. One of the best-preserved tombs contained six skeletons, gold and silver jewelry, cookware, a spearhead, and intact pottery vessels. Next to the pottery, the researchers found four lightly baked clay cylinders with what seemed to be alphabetic writing on them.

Maybe they detail the contents of a vessel, or maybe where the vessel came from, or who it belonged to. Without a means to translate the writing, the researchers can only speculate.

Using carbon-14 dating techniques, researchers confirmed the ages of the tombs, the artifacts, and the writing.

The results were presented  at the American Society of Overseas Research's Annual Meeting on Nov 21st.

How humans evolved to be 'energetically unique'

Humans, it turns out, possess much higher metabolic rates than other mammals, including our close relatives, apes and chimpanzees, finds a Harvard study. Having both high resting and active metabolism, researchers say, enabled our hunter-gatherer ancestors to get all the food they needed while also growing bigger brains, living longer, and increasing their rates of reproduction.

Humans are off-the-charts different from any creature that we know of so far in terms of how we use energy.

The paper, published in Proceedings of the National Academy of Sciences, challenges a previous consensus that human and non-human primates' metabolic rates are either the same or lower than would be expected for their body size.

Using a new comparison method that they say better corrects for body size, environmental temperature, and body fat, the researchers found that humans, unlike most mammals including other primates, have evolved to escape a tradeoff between resting and active metabolic rates.

Animals take in calories through food and, like a bank account, spend them on expenses mostly divided between two broad metabolic categories: resting and physical activity.

In other primates, there is a distinct tradeoff between resting and active metabolic rates, which helps explain why chimpanzees, with their large brains, costly reproductive strategies, and lifespans, and thus high resting metabolisms, are "couch potatoes" who spend much of their day eating.

Generally, the energy animals spend on metabolism ends up as heat, which is hard to dissipate in warm environments. Because of this tradeoff, animals such as chimpanzees who spend a great deal of energy on their resting metabolism and also inhabit warm, tropical environments, have to have low activity levels.

"Humans have increased not only our resting metabolisms beyond what even chimpanzees and monkeys have, but—thanks to our unique ability to dump heat by sweating—we've also been able to increase our physical activity levels without lowering our resting metabolic rates.

The result is that we are an energetically unique species.

The team's analysis shows that monkeys and apes evolved to invest about 30 to 50% more calories in their resting metabolic rates than other mammals of the same size, and that humans have taken this to a further extreme, investing 60% more calories than similar-sized mammals.

Andrew K. Yegian et al, Metabolic scaling, energy allocation tradeoffs, and the evolution of humans' unique metabolism, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2409674121

UTIs are extraordinarily common but kidney infections are not—now we know know why

Infections in the lower urinary tract rarely migrate to the kidneys, but the precise mechanism that the human body employs to keep the twin organs disease-free has remained a medical mystery—until now.

A multidisciplinary team solved the conundrum in an elegant series of experiments. Researchers found that highly specialized biological structures called neutrophil extracellular traps—NETs—are pivotal in protecting the kidneys from infection.

NETs are sticky webs of wispy strands that quite literally serve as traps. They ensnare bacteria that attempt to migrate northward to the kidneys from the lower urinary tract. NETs add to an array of antimicrobial activities mounted by the body to beat back infection.

Writing in Science Translational Medicine, the researchers presented compelling evidence that sticky mesh-like immune NETs serve as a crucial antibacterial defense against infection. The team's study not only revealed the presence of NETs in the urinary tract but also answered a longstanding question in UTI research: What spares the kidneys from pathogens?

"These findings highlight the role of NETosis in preventing ascending infections in the urinary tract.

NETosis refers to the formation of NETs, which prevent any of the various species of bacteria—E. coli, Enterococcal faecalis, Proteus mirabilis, among others—from migrating upward from the bladder to the kidneys. The study focused on E. coli, the most common bacterial cause of UTIs.

The process of NETosis is another wonder of human biology. It reveals how the body, and more specifically, the immune system, creates structures to ensnare pathogens. The key entity in NETosis is the neutrophil, an immune cell, which is signaled to undergo a unique form of cell death. As it succumbs, the neutrophil releases its DNA, histones, and granule proteins, leaving behind a mesh-like structure, a net. E. coli and other bacteria become entrapped just as insects are snared by a spider's web. The process of NETosis isn't rare because NETs are found in the urine of healthy people, the researchers confirmed.

Andrew P. Stewart et al, Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adh5090

Scientists create a 'minimal cell membrane' with just two lipids

Lipids, or fats, are essential to life. They form the membranes around cells, protecting them from the outside. In nature, there is an enormous diversity of lipids, with each organism having its own unique combination. But what are the minimum lipid requirements for a cell to survive?

A research team   showed that cells can function with just two lipids. They created a cell with a minimal, adaptable membrane, offering a unique platform to study how lipid complexity evolved and how it can be engineered for synthetic life. Their findings are published in Nature Communications.

Membranes are like bubbles that encapsulate cells and separate them from their surroundings. Membranes also serve as platforms where molecules interact, coordinating processes essential to life.

"There is an enormous diversity of lipids in nature, and almost every organism has its own set of lipids, known as lipidome. Human cells, for example, employ hundreds of different types of lipids. Yet, these different mixtures of lipids, all provide solutions to the same key evolutionary challenges: creating a stable barrier and organizing biomolecules in space and time.

For their study, the group started with mycoplasma mycoides, a naturally simple pathogenic bacterium. Unlike most cells, mycoplasma cannot make its own lipids and must instead use those provided by its host. By systematically supplementing cells with different lipid combinations, the researchers narrowed down the essential combination needed for survival and division.

They found that the cells can survive on a "diet" of just two lipids: cholesterol and another so-called bilayer-forming lipid, phosphatidylcholine.

These two lipids are not necessarily the only ones that could support life but having both a bilayer-forming lipid, which provides the basic structure for the cell membrane, and a non-bilayer-forming lipid, such as cholesterol, which adds stability, seems to be a fundamental requirement.

The team observed the cells with a minimal lipid diet under an electron microscope and saw dramatic effects on cell shape and size. Some cells grew up to ten times their usual size, while others formed unusual shapes and deformations.

The researchers observed that  about half of the cells with only two lipids appeared completely normal. They were round and divided well. Despite the drastic reduction in lipid complexity, they continued to function surprisingly well.

Reverse engineering the complexity of life

Having identified the minimal lipid diet, the researchers applied it to a "minimal cell" called JVCI-Syn3A, which was engineered at the J. Craig Venter Institute to contain only the genes essential for survival. Now, with both a minimal genome and lipidome, this cell provides a powerful new tool for synthetic biology.

This minimal cell system provides a unique platform to study how lipids support life. Using the principles of bottom-up synthetic biology, researchers can now reintroduce different parts of the lipidome in a directed way and explore the corresponding changes in cell function.

This knowledge could one day help us design synthetic cells with bespoke membranes for special applications in biotechnology and medicine.

Isaac Justice et al, A tuneable minimal cell membrane reveals that two lipid species suffice for life, Nature Communications (2024). DOI: 10.1038/s41467-024-53975-y

Did you know that birds are separating and divorcing too?

Bird divorce rates may be linked to fluctuations in rainfall

A 16-year study on a closed population of Seychelles warblers (Acrocephalus sechellensis) on Cousin Island, Seychelles, has uncovered significant findings about how environmental factors—specifically rainfall—affect the stability of pair bonds in birds.

An international team of researchers  found that fluctuations in rainfall prior to and during the breeding season significantly influence the likelihood of "divorce" between mates, highlighting the broader implications of climate cahnge for animal reproduction and conservation. The study is published in the Journal of Animal Ecology.

Divorce, in the context of socially monogamous species, refers to the termination of a pair bond while both individuals are still alive. This mating strategy is often associated with poor reproductive success and has been observed in various bird species. However, the relationship between environmental factors, particularly climate fluctuations, and divorce is the new way of studying the problem.

Social monogamy implies that two birds have formed a pair bond and associate with the same partner, usually over many years and even lifetimes. Pair-bonded birds usually live and raise young together.

Researchers analyzed 16 years of data and found a complex, non-linear relationship between  rainfall patterns and divorce rates, with divorce being more likely during years of both low and high rainfall.

This relationship was notably influenced by an extreme climatic event—the 1997 El Niño-induced rainfall spike.

Part 1

The study identified a quadratic relationship between rainfall and divorce rates, with the highest rates of divorce occurring in years with either extremely low or high rainfall during the breeding season.

An extreme rainfall event in 1997 was a significant outlier in the data, with exceptionally high rainfall correlating with a sharp increase in divorce rates. When this event was excluded from the analysis, a clearer negative relationship between rainfall and divorce emerged.

Despite rainfall impacting divorce rates, the study found no direct link between reproductive success (i.e., the number of offspring produced) and the likelihood of divorce, suggesting that other, as yet unidentified, factors may be influencing partnership stability.

This study adds to the growing body of evidence showing how environmental factors, particularly those linked to climate change, can directly influence the social dynamics and reproductive strategies of wildlife.

As climate change intensifies, it is critical to understand how fluctuations in environmental conditions, such as rainfall, affect the stability of socially monogamous species.

This research not only enhances our understanding of animal behavior in the face of climate variability but also provides valuable insights that could inform conservation efforts for species vulnerable to the effects of climate change.

 A. A. Bentlage et al, Rainfall is associated with divorce in the socially monogamous Seychelles warbler, Journal of Animal Ecology (2024). DOI: 10.1111/1365-2656.14216

Part 2

How cancer cells fend off starvation and death from chemotherapy

Laboratory experiments with cancer cells have revealed two ways in which tumors evade drugs designed to starve and kill them.

While chemotherapies successfully treat cancers and extend patients' lives, they are known not to work for everyone for long, as cancer cells rewire the process by which they convert fuel into energy (metabolism) to outmaneuver the drugs' effects. Many of these drugs are so-called antimetabolics, disrupting cell processes needed for tumor growth and survival.

Three such drugs used in the study—raltitrexed, N-(phosphonacetyl)-l-aspartate (PALA), and brequinar—work to prevent cancer cells from making pyrimidines, molecules that are an essential component to genetic letter codes, or nucleotides, that make up RNA and DNA.

Cancer cells must have access to pyrimidine supplies to produce more cancer cells and to produce uridine nucleotides, a primary fuel source for cancer cells as they rapidly reproduce, grow, and die. Disrupting the fast-paced but fragile pyrimidine synthesis pathways, as some chemotherapies are designed to do, can rapidly starve cancer cells and spontaneously lead to them dying (apoptosis).

This new  study shows how cancer cells survive in an environment made hostile by the persistent shortage of the energy from glucose (the chemical term for blood sugar) needed to drive tumor growth.

This better understanding of how cancer cells evade the drugs' attempts to kill them in a low-glucose environment, the researchers say, could lead to the design of better or more effective combination therapies.

Publishing in the journal Nature Metabolism online Nov. 26, study results showed that the low-glucose environment inhabited by cancer cells, or tumor microenvironment, stalls cancer cell consumption of existing uridine nucleotide stores, making the chemotherapies less effective.

Normally, uridine nucleotides would be made and consumed to help make the genetic letter codes and fuel cell metabolism. But when DNA and RNA construction is blocked by these chemotherapies, so too is the consumption of uridine nucleotide pools, the researchers found, as glucose is needed to change one form of uridine, UTP, into another usable form, UDP-glucose.

The irony, researchers say, is that a low-glucose tumor microenvironment is in turn slowing down cellular consumption of uridine nucleotides and presumably slowing down rates of cell death. Researchers say cancer cells need to run out of pyrimidine building blocks, including uridine nucleotides, before the cells will self-destruct.

In other experiments, low-glucose tumor microenvironments were also unable to activate two proteins, BAX and BAK, sitting on the surface of mitochondria, a cell's fuel generator. Activation of these trigger proteins disintegrates the mitochondria, and instantly sets off a series of caspase enzymes that help initiate apoptosis (cell death).

Conclusion of the study:  low glucose slows down the consumption and exhaustion of uridine nucleotides needed to fuel cancer cell growth and hinders resulting apoptosis, or death, in cancer cells.

Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01166-w

Intestinal infections can change bile composition, leading to changes in immune function

Intestinal infections can change the composition of liver bile, leading to changes in immune function and gut bacteria, potentially helping fight off harmful bacteria.

Researchers have identified a new axis of host defense by studying what happens during enteric infection—a term that encompasses all types of intestinal infections including so-called "stomach flu."

A new study from infectious disease investigators 

uncovers how bile, a solution produced by the liver and responsible for the absorption of fat, plays a role in the fight against infections.

While the study was conducted in mice, the researchers anticipate that the findings likely apply to humans as well. Results are published in Nature Microbiology.

The changes the researchers  detected in the composition of bile with infection are beneficial for the intestine to clear infection. 

These findings findings reveal the intricate and dynamic nature of bile composition, shedding new light on the liver's critical role in defending the intestine from infection. These insights enhance our understanding of the liver's broader functions in regulating physiological stability and metabolic processes.

Part 1

Using a mouse model, this study used global metabolic analysis to investigate changes in metabolites during an enteric infection. The mice were infected with one of two pathogens, L. monocytogenes, which replicates in the intestine, liver and gall bladder, or C. rodentium, which replicates in the caecum and colon.

The different infection groups led to both shared and specific changes in bile metabolites. Moreover, hundreds of new metabolites that are in the bile metabolome were described. More specifically, the researchers found that enteric infection dynamically changes the composition of bile in order to provide intestinal defense.
While these findings bridge a large gap in knowledge regarding bile composition, the researchers note that the 812 bile metabolites identified in this study likely only represent a subset of all bile metabolites.

Ting Zhang et al, Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis, Nature Microbiology (2024). DOI: 10.1038/s41564-024-01862-z

Part 2

Tumor cell death can backfire, strengthening cancer's defenses and limiting immunotherapy success

A new study has uncovered an unexpected way cancer cells can escape the immune system, making it harder for treatments to work. The study, published in Cancer Cell, explains how a type of cancer cell death can actually make tumors grow faster by turning off the immune system's ability to fight the cancer.

Researchers  focused on a form of cell death called necroptosis. Previously thought to help the immune system fight cancer, researchers found that when cancer cells die in this way, they can release a molecule called interleukin-1α.

This molecule helps create an environment in the tumor that weakens the immune response, preventing T cells from attacking the cancer.

People thought necroptosis would help the immune system fight cancer, but instead, it seems to make things worse by helping tumors grow. This study shows that interleukin-1α is key to this process, and by blocking it, we might be able to help the immune system do its job.

The study also found that interleukin-1α is released by cancer cells responding to chemotherapy, which could explain why some treatments don't work as well as expected. But there's good news: By blocking interleukin-1α, researchers were able to improve the immune response and make cancer treatments like chemotherapy and immunotherapy more effective in animal models.

By blocking the actions of interleukin-1α, we could make current cancer treatments more successful. Additionally, targeting interleukin-1α can reduce the toxicity associated with chemotherapy, meaning this approach could help patients respond to and better tolerate therapy.

Researchers also discovered that lower levels of interleukin-1α are linked to better outcomes, especially in patients treated with chemotherapy. This suggests that interleukin-1α could be used as a marker to predict how well cancer treatments might work for different patients.

Kay Hänggi et al, Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity, Cancer Cell (2024). DOI: 10.1016/j.ccell.2024.10.014