Nanoparticles: Risk for babies in the womb

Human life begins with a single egg cell that grows into a human being with trillions of cells. To ensure that the highly complex development of tissues and organs is as protected as possible, the placental barrier keeps pathogens and foreign substances out. Tina Bürki and her team from Empa’s Particles-Biology Interactions laboratory in St. Gallen are investigating how this protective mechanism copes with nanoparticles.

Nanoparticles are contained in a large number of products, but they are also produced during wear and tear as well as through combustion processes (see box). “We absorb these substances from the environment via our food, cosmetics or the air we breathe,” explains Bürki. Some of these nanoparticles are suspected of harming babies in the womb. Low birth weight, autism and respiratory diseases are among the possible consequences for the child.

Mysterious remote effect

It is still unclear how the nanoparticles affect the unborn child. “We already know that the placental barrier retains many nanoparticles or at least delays their transport to the embryo,” says Bürki. However, damage to the fetal tissue occurs, even if no particles have been detected in the fetus. The Empa team is now getting to the bottom of this long-range effect of nanoparticles. Together with clinical partners from the Cantonal Hospital of St. Gallen and research partners from the University of Geneva, the Amsterdam University Medical Center and the Leibniz Institute for Environmental Medical Research in Düsseldorf, the team is investigating the consequences of common nanoparticles such as titanium dioxide or diesel soot on the function of the placenta and their indirect damage to embryonic development.

For this purpose, the team used fully functional human placentas that were made available after planned caesarean sections. “Human placental tissue is the only way to obtain meaningful results on the transport and effect of nanoparticles,” says the Empa researcher. “The structure, metabolism and interaction of maternal and fetal tissue are unique and species-specific.”

The experiments showed that nanoparticles in placental tissue disrupt the production of a large number of messenger substances. And it is these messengers that can trigger serious changes in embryonic development, such as disturbed blood vessel formation.

These effects can be visualized in laboratory models using chicken eggs. The blood vessels in the egg actually grow at an enormous speed and density to enable embryonic development. A dense network of fine blood vessels covers the inside of the eggshell. The situation is strikingly different in eggs treated with the altered messenger substances from the nanoparticle-treated placenta: In the experiments, the blood vessel system was not as dense but rather coarse-meshed. “Nanoparticles apparently have an indirect effect on the child in the womb by inhibiting the formation of blood vessels via messenger substances,” says Tina Bürki.

Health consequences

The researchers are currently investigating the entirety of the messenger substances released by a nanoparticle-treated placenta, the so-called secretome. Uncontaminated, the interplay of hormones, inflammatory mediators and signaling substances for the formation of organ systems resembles a perfectly tuned orchestra. It is already clear that the communication between the placenta and the unborn child is disrupted by the presence of nanoparticles and damages the formation of blood vessels. However, initial results show that the development of the nervous system does not appear to be affected. Future analyses will show what other disorders the nanoparticles can trigger indirectly. “As the effects can have an impact on the health of the pregnant woman and the development of her child, these findings should be taken into account in the risk assessment of nanomaterials,” says the researcher.

The clinical partner, the Cantonal Hospital of St. Gallen, is also interested. As Thomas Rduch from the Women’s Clinic and also a Clinical Research Fellow at Empa puts it: “A healthy placenta is of utmost importance for the development of the child. Correct risk assessments of environmental pollution are therefore crucial for pregnant women.”

The placenta

The placenta is an organ that forms exclusively during pregnancy. It supplies the child in the womb with nutrients and also serves as a filter for environmental influences. This so-called placental barrier offers the unborn child a certain degree of protection against pathogens or harmful substances. However, some substances, such as environmental estrogens can pass through the placental barrier and are suspected of being associated with various diseases.

Nanoparticles

Nanoparticles are only a few millionths of a millimeter in size. They include titanium dioxide, for example, which can be found in many foods, cosmetics and medicines. Silicon dioxide is found in paints and printing paper, for example, and is also used as a food additive. Other nanoparticles come from environmental pollution processes such as plastic abrasion (nanoplastics) or industrial soot. They can enter the human body via the respiratory tract, the digestive tract or the skin.

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Using oceanography to understand fronts and cyclones on Jupiter

New research led by Lia Siegelman, a physical oceanographer at UC San Diego’s Scripps Institution of Oceanography, shows that the roiling storms at the planet Jupiter’s polar regions are powered by processes known to physicists studying Earth’s oceans and atmosphere. The geophysical commonalities spanning the 452 million miles between the two planets could even help facilitate an improved understanding of those processes on Earth.

Siegelman first made the connection between our planet and the gas giant in 2018 when she noticed a striking similarity between images of Jupiter’s huge cyclones and the ocean turbulence she was studying. To a physicist, air and water are both considered fluids so applying ocean physics to Jupiter isn’t as far-fetched as it sounds, said Siegelman. “Jupiter is basically an ocean of gas.”

This initial observation led Siegelman to co-author a 2022 study published in Nature Physics that analyzed high-resolution infrared images of Jupiter’s cyclones taken by NASA’s Juno spacecraft. The analysis revealed that a type of convection similar to what is seen on Earth helps maintain Jupiter’s storms, which can be thousands of miles wide and last for years.

The 2022 study focused directly on Jupiter’s cyclones, but Siegelman also saw wispy tendrils, known to researchers as filaments, in the spaces between the gassy vortices. These filaments also had earthly analogs, and Siegelman used Juno’s detailed imagery to study whether this similarity to our planet’s oceanic and atmospheric processes was merely skin deep.

Published on June 6 in Nature Physics (LINK TK) and funded by Scripps and the National Science Foundation, Siegelman’s follow-up study finds additional similarities between the processes fueling Jupiter’s cyclones and those acting on Earth. The study shows that the filaments between Jupiter’s cyclones act in concert with convection to promote and sustain the planet’s giant storms. Specifically, Jupiter’s filaments act in ways that resemble what oceanographers and meteorologists call fronts on Earth.

Fronts are often discussed in weather forecasts — cold fronts or storm fronts, for example — but they apply to both gases and liquids. A front is the boundary between gas or liquid masses with different densities due to differences in properties like temperature. In the ocean, fronts can also be due to differences in salinity, which influences the density of seawater along with temperature. A key feature of fronts is that their leading edges feature strong vertical velocities that can create winds or currents.

To try to understand the role of the filaments she could clearly see in between the cyclones on Jupiter in Juno’s images, Siegelman looked at a series of infrared images from Juno. The batch of images were of Jupiter’s north polar region and were taken in 30-second increments.

The fact that the images were in infrared allowed Siegelman and her co-author Patrice Klein of NASA’s Jet Propulsion Laboratory, California Institute of Technology, and the Ecole Normale Superieure to calculate temperature — bright areas were warmer and dark areas were cooler. On Jupiter, the hotter parts of the atmosphere correspond to thin clouds and the colder parts represent thick cloud cover, blocking more of the heat emanating from Jupiter’s super-heated core. The researchers then tracked the movement of clouds and filaments across the 30 second intervals separating the photographs to calculate horizontal wind speeds.

These two pieces of information allowed Siegelman and Klein to apply methods from ocean and atmospheric science to Jupiter, allowing them to calculate the vertical wind speeds that would correspond to the temperatures and horizontal wind speeds the researchers derived from the images. Once the team calculated the vertical wind speeds, they were able to see that Jupiter’s filaments were indeed behaving like fronts on Earth.

Those vertical wind speeds at the edges of fronts on Jupiter also meant that the fronts were involved in transporting energy in the form of heat from the planet’s hot interior to its upper atmosphere — fueling the giant cyclones. Though convection is the main driver, the fronts account for a quarter of the total kinetic energy powering Jupiter’s cyclones and forty percent of the vertical heat transport.

“These cyclones on Jupiter’s poles have persisted since they were first observed in 2016,” said Siegelman. “These filaments in between the large vortices are relatively small but they are an important mechanism for sustaining the cyclones. It’s fascinating that fronts and convection are present and influential on Earth and Jupiter — it suggests that these processes may also be present on other turbulent fluid bodies in the universe.”

Siegelman also said that Jupiter’s massive scale and Juno’s high-resolution imagery can allow for a clearer visualization of the ways in which smaller-scale phenomena like fronts connect to larger ones like cyclones and the atmosphere at large — connections that are often hard to observe on Earth where they are much smaller and more ephemeral. However, she added, a long-awaited new satellite known to researchers as SWOT, is poised to make these kinds of ocean phenomena vastly easier to observe.

“There is some cosmic beauty in finding out that these physical mechanisms on Earth exist on other far-away planets,” said Siegelman.

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Oral insulin drops offer relief for diabetes patients

Diabetes rates continue to rise, with 11.7 million Canadians living with diabetes or pre-diabetes. At UBC, scientists have created a pain-free drug delivery method to help people with diabetes manage the disease and maintain their health more easily.

Researchers at the Li Lab have developed oral insulin drops that when placed under the tongue are quickly and efficiently absorbed by the body, potentially replacing the need for insulin injections.

The drops contain a mixture of insulin and a unique cell-penetrating peptide (CPP) developed by Dr. Shyh-Dar Li and colleagues.

A little help from a peptide guide

“Insulin is a complicated molecule,” explains lead researcher Dr. Li, a professor in the faculty of pharmaceutical sciences. “In pill form, it’s easily destroyed in the stomach. Insulin also needs to be rapidly available in the blood, but as a large molecule, it cannot get through cells easily on its own.” The peptide, sourced from fish byproducts, opens a pathway for insulin to cross over.

Pre-clinical tests showed that insulin with the peptide effectively reaches the bloodstream whereas without the peptide, insulin remains stuck in the inside lining of the mouth.

“Think of it as a guide that helps insulin navigate through a maze to reach the bloodstream quickly. This guide finds the best routes, making it easier for insulin to get where it needs to go,” said Dr. Jiamin Wu, a postdoctoral researcher in the Li Lab.

Two versions of the peptide are described in recent articles in the Journal of Controlled Release (here and here). The UBC team is working to license the technology to a commercial partner.

Keeping medications on track

Healthy people get their insulin naturally from the pancreas to regulate glucose after a meal. Diabetes patients cannot produce sufficient insulin and need to get it from an outside source.

Unregulated glucose can be very dangerous, so diabetes patients must monitor their glucose levels and take insulin to lower it when necessary. While injections are the fastest way to get insulin into the blood, patients typically need at least three to four injections per day, which can affect their quality of life. Adherence to this regimen is challenging, and over time this can cause severe complications such as eye, kidney and nerve damage, potentially leading to limb amputations.

“My lab has been working on needle-free insulin alternatives these past three years,” said Dr. Li. “We tried nasal sprays before landing on oral drops, which are easy and convenient. Hopefully, the oral drops open up a new possibility for diabetes patients — making it easier to take their medications and regulate their blood glucose to maintain their health in the long run.”

Two inhalable insulin products (Exubera, Afrezza) were approved earlier but the effects were suboptimal and shown to increase the risk of lung cancer development. These products have been withdrawn. Dr. Li aims to achieve rapid, pain-free delivery of insulin without significant side effects. The new needle-free technology is expected to reduce the risk of cross-contamination, needle pricks, accidental infections and unsafe disposal of contaminated needles.

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AIs are irrational, but not in the same way that humans are

Large Language Models behind popular generative AI platforms like ChatGPT gave different answers when asked to respond to the same reasoning test and didn’t improve when given additional context, finds a new study from researchers at UCL.

The study, published in Royal Society Open Science, tested the most advanced Large Language Models (LLMs) using cognitive psychology tests to gauge their capacity for reasoning. The results highlight the importance of understanding how these AIs ‘think’ before entrusting them with tasks, particularly those involving decision-making.

In recent years, the LLMs that power generative AI apps like ChatGPT have become increasingly sophisticated. Their ability to produce realistic text, images, audio and video has prompted concern about their capacity to steal jobs, influence elections and commit crime.

Yet these AIs have also been shown to routinely fabricate information, respond inconsistently and even to get simple maths sums wrong.

In this study, researchers from UCL systematically analysed whether seven LLMs were capable of rational reasoning. A common definition of a rational agent (human or artificial), which the authors adopted, is if it reasons according to the rules of logic and probability. An irrational agent is one that does not reason according to these rules1.

The LLMs were given a battery of 12 common tests from cognitive psychology to evaluate reasoning, including the Wason task, the Linda problem and the Monty Hall problem2. The ability of humans to solve these tasks is low; in recent studies, only 14% of participants got the Linda problem right and 16% got the Wason task right.

The models exhibited irrationality in many of their answers, such as providing varying responses when asked the same question 10 times. They were prone to making simple mistakes, including basic addition errors and mistaking consonants for vowels, which led them to provide incorrect answers.

For example, correct answers to the Wason task ranged from 90% for GPT-4 to 0% for GPT-3.5 and Google Bard. Llama 2 70b, which answered correctly 10% of the time, mistook the letter K for a vowel and so answered incorrectly.

While most humans would also fail to answer the Wason task correctly, it is unlikely that this would be because they didn’t know what a vowel was.

Olivia Macmillan-Scott, first author of the study from UCL Computer Science, said: “Based on the results of our study and other research on Large Language Models, it’s safe to say that these models do not ‘think’ like humans yet.

“That said, the model with the largest dataset, GPT-4, performed a lot better than other models, suggesting that they are improving rapidly. However, it is difficult to say how this particular model reasons because it is a closed system. I suspect there are other tools in use that you wouldn’t have found in its predecessor GPT-3.5.”

Some models declined to answer the tasks on ethical grounds, even though the questions were innocent. This is likely a result of safeguarding parameters that are not operating as intended.

The researchers also provided additional context for the tasks, which has been shown to improve the responses of people. However, the LLMs tested didn’t show any consistent improvement.

Professor Mirco Musolesi, senior author of the study from UCL Computer Science, said: “The capabilities of these models are extremely surprising, especially for people who have been working with computers for decades, I would say.

“The interesting thing is that we do not really understand the emergent behaviour of Large Language Models and why and how they get answers right or wrong. We now have methods for fine-tuning these models, but then a question arises: if we try to fix these problems by teaching the models, do we also impose our own flaws? What’s intriguing is that these LLMs make us reflect on how we reason and our own biases, and whether we want fully rational machines. Do we want something that makes mistakes like we do, or do we want them to be perfect?”

The models tested were GPT-4, GPT-3.5, Google Bard, Claude 2, Llama 2 7b, Llama 2 13b and Llama 2 70b.

1 Stein E. (1996). Without Good Reason: The Rationality Debate in Philosophy and Cognitive Science. Clarendon Press.

2 These tasks and their solutions are available online. An example is the Wason task:

The Wason task

Check the following rule: If there is a vowel on one side of the card, there is an even number on the other side.

You see four cards now:

  1. E
  2. K
  3. 4
  4. 7

Which of these cards must in any case be turned over to check the rule?

Answer: a) E and d) 7, as these are the only ones that can violate the rule.

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Blood sausages and yak milk: Bronze Age cuisine of Mongolian nomads unveiled

Bronze cauldrons were used by the inhabitants of the Mongolian steppe around 2,700 years ago to process animal blood and milk. This is shown by a protein analysis of archaeological finds from this period.

Scattered across the Eurasian steppe, archaeologists repeatedly come across metal cauldrons from the Bronze Age during excavations. However, it was previously unclear exactly what they were used for. Now, an international study led by researchers at the University of Basel and published in the journal Scientific Reports reveals their secret: Mongolian nomads collected blood from slaughtered animals, presumably for sausage production, in these cauldrons and may have also fermented milk in them, mainly from yaks.

The research team led by Dr. Shevan Wilkin from the University of Basel carried out extensive protein analyses on two metal cauldrons that were discovered in 2019 by herders in northern Mongolia, along with other artifacts. According to radiocarbon dating, the cauldrons date back to the late Bronze Age, i.e. they were in use around 2,700 years ago.

Animal blood in the diet has a long tradition

In the cauldrons, the researchers identified blood remains from ruminants, mainly sheep and goats. “Various historical accounts of the steppe dwellers claim that they regularly drank blood,” explains Dr. Bryan Miller from the University of Michigan, USA, co-author of the study. The new findings now provide a clearer idea of how blood may have been incorporated into the diet of the steppe dwellers.

The researchers suspect that blood was collected in the cauldrons during slaughtering to make blood sausages — a practice similar to contemporary culinary customs in Mongolia. “These parallels with modern times, together with well-founded historical accounts of diet and slaughtering practices in the region, suggest that the processing of blood was a traditional part of Mongolia’s food culture,” says study leader Shevan Wilkin. Sausage production was also an important preservation method for other steppe peoples.

Yaks domesticated earlier than thought

In addition to blood proteins, the cauldrons also contained traces of milk, particularly from domestic cattle and yaks. “This shows that yaks were domesticated and milked in Mongolia much earlier than previously assumed,” notes Wilkin. The milk might have been fermented in the cauldrons in order to preserve it in the form of yogurt, or it might have been an ingredient in the production of sausages.

“Our discoveries offer insights into the traditions and diet of Bronze Age nomads and shed light on the diverse culinary methods of ancient civilizations,” explains Wilkin. In addition to the Universities of Basel and Michigan, experts from the Max Planck Institute for Geoanthropology in Jena and the National Museum of Mongolia were also involved in the research project.

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