Current figures show that around one in six pregnant women worldwide are affected by a special form of diabetes known as gestational diabetes. According to the Robert Koch Institute, 63,000 women in Germany were affected by the disease in 2021, and the trend is increasing. These numbers are alarming because excessively high blood sugar levels during pregnancy are associated with negative consequences for mother and child. This increases the risk of affected women developing type 2 diabetes later on and their children have a higher risk of developing metabolic disorders and being overweight.

Long-Term Effect of Metformin on Offspring is Unclear

For several years, the placenta-crossing oral antidiabetic agent metformin has been increasingly gaining importance as an alternative to insulin administration when lifestyle changes show no success during the treatment of gestational diabetes. However, there are currently only a few studies on the long-term effects of metformin on the health of offspring. It is known that metformin has an impact on the AMPK signaling pathway, which regulates the networking of nerve cells during brain development.

The interdisciplinary team of DIfE researchers led by Junior Research Group Leader Dr. Rachel Lippert therefore grappled with two central questions: Is metformin treatment only beneficial for the mother or also the child? And does metformin treatment lead to long-term negative physiological changes in the offspring, especially in connection with the development of neuronal circuits in the hypothalamus, a critical region in the regulation of energy homeostasis?

Mouse Models Shed some Light

To answer the key questions, the researchers used two mouse models to represent the main causes of gestational diabetes:

severe obesity of the mother before pregnancy and excessive weight gain during pregnancy. These metabolic states were achieved by means of different feeding patterns, with the mice receiving either a high-fat or control diet. The antidiabetic treatment of female mice and their offspring took place during the lactation period as this corresponds to the third trimester of a human pregnancy in terms of brain development.

Treatment involved insulin, metformin, or a placebo, whereby the dosage was based on standard human treatments. The research team collected data on the body weight of the mice, analyzed various metabolic parameters and hormones, and examined molecular signaling pathways in the hypothalamus.

Maternal Metabolic State is Crucial

“As a result of antidiabetic treatment in the early postnatal period, we were able to identify alterations in the weight gain and hormonal status of the offspring, which were critically dependent on the metabolic state of the mother,” explains Lippert. Furthermore, sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure were also observed. Together with the metformin-induced shift in the examined hormone levels, the results indicate that the maternal metabolic state must be taken into account before starting the treatment of gestational diabetes.

Focusing on Prevention

According to Rachel Lippert, treatment of gestational diabetes in future could entail developing a medication that is available for all and does not cross the placenta. “Given the increasing prevalence, education about gestational diabetes and preventive measures are of vital importance. If we can find a way to manage lifestyle and diet more proactively, we are in a better position to exploit the potential of gestational diabetes treatment,” says Lippert.

Scientists use the bony plates that make up aetosaur armor to identify different species and usually don’t have many fossil skeletons to work with. But a new study led by researchers at The University of Texas at Austin centers on an aetosaur suit of armor that has most of its major parts intact.

The suit — called a carapace — is about 70% complete and covers each major region of the body.

“We have elements from the back of the neck and shoulder region all the way to the tip of the tail,” said William Reyes, a doctoral student at the UT Jackson School of Geosciences who led the research. “Usually, you find very limited material.”

The research was published in The Anatomical Record.

Reyes and his collaborators used the armor to identify the specimen as a new aetosaur species — which they named Garzapelta muelleri. The name “Garza” recognizes Garza County in northwest Texas, where the aetosaur was found, and “Pelta” is Latin for shield, a nod to aetosaurs’ heavily fortified body. The species name “muelleri” honors the paleontologist who originally discovered it, Bill Mueller.

Garzapelta lived about 215 million years ago and resembled a modern American crocodile — but with much more armor.

“Take a crocodile from modern day, and turn it into an armadillo,” said Reyes.

The bony plates that covered Garzapelta and other aetosaurs are called osteoderms. They were embedded directly in the skin and formed a suit of armor by fitting together like a mosaic. In addition to having a body covered in bony plates, Garzapelta’s sides were flanked by curved spikes that would have offered another layer of protection from predators. Although crocodiles today are carnivores, scientists think that aetosaurs were primarily omnivorous.

The spikes on Garzapelta are very similar to those found in another aetosaur species, but surprisingly, researchers found that the two species are only distantly related. The similarities, they discovered, are an example of convergent evolution, the independent evolution of similar traits in different species. The development of flight in insects, birds, mammals and now-extinct pterosaurs is a classic example of this phenomenon.

According to Reyes, an array of unique features on Garzapelta’s plates clearly marked it as a new species. They range from how the plates fit together to unique bumps and ridges on the bones. However, figuring out where Garzapelta fit into the larger aetosaur family tree was more of challenge. Depending on which portion of the armor the researchers emphasized in their analysis, Garzapelta would end up in very different places. Armor that ran down its back resembled armor from one species, while its midsection spikes resembled armor from another.

Once the researchers determined that the spikes evolved independently, they were able to work out where Garzapelta fit best among other aetosaur species. Nevertheless, Reyes said the research shows how convergent evolution can complicate things.

“Convergence of the osteoderms across distantly related aetosaurs has been noted before, but the carapace of Garzapelta muelleri is the best example of it and shows to what extent it can happen and the problems it causes in our phylogenetic analyses,” Reyes said.

Garzapelta is part of the Texas Tech University fossil collections. It spent most of the past 30 years on a shelf before Reyes encountered it during a visit. Bill Parker, an aetosaur expert and park paleontologist at Petrified Forest National Park who was not part of the research, said that university and museum collections are a critical part of making this type of research possible.

“These specimens weren’t just dug in the field yesterday,” he said. “They’ve been sitting in the museum for decades and it just takes someone like Will to come along and finally decide to study them and make them come to life.”

In addition to different species having different armor, it’s possible that an animal’s age or sex could also affect armor appearance. Reyes is currently exploring these questions by studying aetosaur fossils in the Jackson School’s collection, most of which were found during the 1940s as part of excavations done by the Works Progress Administration.

The research was funded by the National Science Foundation and the Jackson School.

The study co-authors are Jeffrey Martz, an associate professor at the University of Houston-Downtown, and Bryan Small, a research associate at the Museum of Texas Tech University.

This could allow the development of bioinspired optical materials with possible applications ranging from invisible cloaking devices to coatings to more efficiently harvest solar energy, said Tak-Sing Wong, professor of mechanical engineering and biomedical engineering. Wong led the study, which was published today (March 18) in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The unique, tiny particles have an unusual soccer ball-like geometry with cavities, and their exact purpose for the insects has been something of a mystery to scientists since the 1950s. In 2017, Wong led the Penn State research team that was the first to create a basic, synthetic version of brochosomes in an effort to better understand their function.

“This discovery could be very useful for technological innovation,” said Lin Wang, postdoctoral scholar in mechanical engineering and the lead author of the study. “With a new strategy to regulate light reflection on a surface, we might be able to hide the thermal signatures of humans or machines. Perhaps someday people could develop a thermal invisibility cloak based on the tricks used by leafhoppers. Our work shows how understanding nature can help us develop modern technologies.”

Wang went on to explain that even though scientists have known about brochosome particles for three-quarters of a century, making them in a lab has been a challenge due to the complexity of the particle’s geometry.

“It has been unclear why the leafhoppers produce particles with such complex structures,” Wang said, “We managed to make these brochosomes using a high-tech 3D-printing method in the lab. We found that these lab-made particles can reduce light reflection by up to 94%. This is a big discovery because it’s the first time we’ve seen nature do something like this, where it controls light in such a specific way using hollow particles.”

Theories on why leafhoppers coat themselves with a brochosome armor have ranged from keeping them free of contaminants and water to a superhero-like invisibility cloak. However, a new understanding of their geometry raises a strong possibility that its main purpose could be the cloak to avoid predators, according to Tak-Sing Wong, professor of mechanical engineering and biomedical engineering and corresponding author of the study.

The researchers have found that the size of the holes in the brochosome that give it a hollow, soccer ball-like appearance is extremely important. The size is consistent across leafhopper species, no matter the size of the insect’s body. The brochosomes are roughly 600 nanometers in diameter — about half the size of a single bacterium — and the brochosome pores are around 200 nanometers.

“That makes us ask a question,” Wong said. “Why this consistency? What is the secret of having brochosomes of about 600 nanometers with about 200-nanometer pores? Does that serve some purpose?”

The researchers found the unique design of brochosomes serves a dual purpose — absorbing ultraviolet (UV) light, which reduces visibility to predators with UV vision, such as birds and reptiles, and scattering visible light, creating an anti-reflective shield against potential threats. The size of the holes is perfect for absorbing light at the ultraviolet frequency.

This potentially could lead to a variety of applications for humans using synthetic brochosomes, such as more efficient solar energy harvesting systems, coatings that protect pharmaceuticals from light-induced damage, advanced sunscreens for better skin protection against sun damage and even cloaking devices, researchers said. To test this, the team first had to make synthetic brochosomes, a major challenge in and of itself.

In their 2017 study, the researchers mimicked some features of brochosomes, particularly the dimples and their distribution, using synthetic materials. This allowed them to begin understanding the optical properties. However, they were only able to make something that looked like brochosomes, not an exact replica.

“This is the first time we are able to make the exact geometry of the natural brochosome,” Wong said, explaining that the researchers were able to create scaled synthetic replicas of the brochosome structures by using advanced 3D-printing technology.

They printed a scaled-up version that was 20,000 nanometers in size, or roughly one-fifth the diameter of a human hair. The researchers precisely replicated the shape and morphology, as well as the number and placement of pores using 3D printing, to produce still-small faux brochosomes that were large enough to characterize optically.

They used a Micro-Fourier transform infrared (FTIR) spectrometer to examine how the brochosomes interacted with infrared light of different wavelengths, helping the researchers understand how the structures manipulate the light.

Next, the researchers said they plan to improve the synthetic brochosome fabrication to enable production at a scale closer to the size of natural brochosomes. They will also explore additional applications for synthetic brochosomes, such as information encryption, where brochosome-like structures could be used as part of an encryption system where data is only visible under certain light wavelengths.

Wang noted that their brochosome work demonstrates the value of a biomimetic research approach, where scientists looks to nature for inspiration.

“Nature has been a good teacher for scientists to develop novel advanced materials,” Wang said. “In this study, we have just focused on one insect species, but there are many more amazing insects out there that are waiting for material scientists to study, and they may be able to help us solve various engineering problems. They are not just bugs; they are inspirations.”

Along with Wong and Wang from Penn State, other researchers on the study include Sheng Shen, professor of mechanical engineering, and Zhuo Li, doctoral candidate in mechanical engineering, both at Carnegie Mellon University, who contributed to the simulations in this study. Wang and Li contributed equally to this work, for which the researchers have filed a U.S. provisional patent. The Office of Naval Research supported this research.