In a study published recently in npj biosensing, researchers from Osaka University have revealed that high liquid flow rates could cause aggregation-prone proteins to start sticking together.

Amyloidosis is the basis of several serious diseases, such as Alzheimer disease and Parkinson disease. This process involves the formation of amyloid fibrils, crystal-like collections of misfolded proteins that clump together when the proteins are highly concentrated (supersaturated) in liquids like blood or cerebrospinal fluid.

“Amyloidosis is a serious concern in our aging society, as elderly individuals are more likely to develop these conditions,” says lead author of the study Yuji Goto. “Although studies have shown that supersaturation is a necessary condition for amyloid fibril formation, the factors that actually induce protein aggregation in supersaturated fluids remain unclear.”

To address this, the researchers ran a model amyloid-forming protein, hen egg white lysozyme, through a peristaltic pump similar to those used for dialysis. They then used fluorescence detection to monitor hen egg white lysozyme amyloid formation as it was propelled through the pump system.

“The results were highly intriguing,” explains Hirotsugu Ogi, senior author. “Flow through the peristaltic pump system effectively triggered amyloid formation by hen egg white lysozyme.”

Next, the researchers tested amyloid-forming proteins associated with human disease, including a-synuclein, amyloid b 1-40, and b2-microglobulin, and found that they also formed amyloids in the peristaltic pump system. Their calculations showed that the shear stress on the liquid caused by the pumping motion mechanically broke supersaturation to induce amyloid formation.

“Our findings suggest that shear flow forces in various fluids in our body, such as blood and cerebrospinal fluid, could trigger amyloid formation,” says Goto.

Given that some medical procedures like dialysis use peristaltic pumps, it is possible that this could be another trigger of amyloidosis. Understanding the effects of shear forces on protein supersaturation could clarify how amyloid aggregates begin to form nucleation and help develop treatment strategies.

In an article published this month in Applied Physics Express, a multi-institutional research team led by Osaka University announced that they have successfully synthesized an ultrathin vanadium dioxide film on a flexible substrate, in a way that preserves the film’s electrical properties.

Vanadium dioxide is well known in the scientific community for its ability to transition between conductor and insulator phases at nearly room temperature. This phase transition underpins smart and adaptable electronics that can adjust to their environment in real time. But there is a limit to how thin vanadium dioxide films can be, because making a material too small affects its ability to conduct or insulate electricity.

“Ordinarily, when a film is placed on a hard substrate, strong surface forces interfere with the atomic structure of the film and degrade its conductive properties,” explains Boyuan Yu, lead author of the study.

To overcome this limitation, the team prepared their films on two-dimensional hexagonal boron nitride (hBN) crystals; hBN is a highly stable soft material that does not have strong bonds with oxides and thus does not excessively strain the film or spoil its delicate structure.

“The results are truly surprising,” says Hidekazu Tanaka, senior author. “We find that by using this soft substrate, the material structure is very nearly unaffected.”

By performing precise spectroscopy measurements, the team was able to confirm that the phase transition temperature of their vanadium dioxide layers remained essentially unchanged, even at thicknesses as thin as 12 nm.

“This discovery significantly improves our ability to manipulate quantum materials in practical ways,” says Yu. “We have gained a new level of control over the transition process, which means we can now tailor these materials to specific applications like sensors and flexible electronics.”

Given that quantum materials like vanadium dioxide play a crucial role in the design of microsensors and devices, this discovery could pave the way for functional and adaptable electronics that can be attached anywhere. The research team is currently working on such devices, as well as exploring ways to incorporate even thinner films and substrates.

“We’ve come up with an explanation for a decades-long contradiction about why retinoic acid works in post-chemotherapy consolidation but has little impact on primary neuroblastoma tumors,” said senior co-corresponding author Paul Geeleher, PhD, St. Jude Department of Computational Biology. “Retinoic acid’s activity heavily depends on the cellular microenvironment.”

The cellular microenvironment is the soup of chemicals, proteins and other signals that surround a cell, and which is unique to that part of the body. For example, the bone marrow microenvironment contains signals to grow blood cells and restructure bone. Metastasized neuroblastoma cells often migrate to bone marrow, where the bone morphogenetic protein (BMP) pathway signaling is highly active. The researchers showed that BMP signaling makes neuroblastoma cells much more vulnerable to retinoic acid.

“Unexpectedly, we found that cells expressing genes from the BMP signaling pathway were very sensitive to retinoic acid,” said co-first and co-corresponding author Min Pan, PhD, St. Jude Department of Computational Biology. “However, since the bone marrow microenvironment causes neuroblastoma cells there to have higher BMP activity, it neatly explained why retinoic acid is very effective at treating those cells during consolidation therapy, but not the primary tumors during up-front treatment.”

Hijacking development to drive metastatic neuroblastoma cell death

Using gene editing technology, the scientists uncovered the relationship between BMP signaling and retinoic acid. They assembled a group of neuroblastoma cell lines susceptible to retinoic acid, then cut out genes to find which were responsible for the drug’s activity. Genes in the BMP pathway had the largest effect while providing a plausible explanation for retinoic acid’s varying outcomes in patients.

“We found that, in neuroblastoma, BMP signaling works with retinoic acid signaling in the same way as during development,” said co-first author Yinwen Zhang, PhD, St. Jude Department of Computational Biology. Zhang characterized how transcription factors, the proteins that bind DNA to regulate gene expression, led to different results in highly retinoic acid-sensitive or insensitive neuroblastoma cells. “If there are a lot of BMP-signaling pathway transcription factors already on DNA, then retinoic acid signaling combines with it to promote downstream cell death-related gene expression. This occurs both in normal embryonic development and neuroblastoma cells in certain microenvironments.”

“We are the first to uncover such an example of ‘hijacking’ a normal embryonic developmental process preserved in cancer that we can exploit therapeutically,” Geeleher said. “Now, we can look for similar processes in other diseases to design less toxic and more effective treatment strategies.”

“Niche partitioning” is one of the most fundamental and essential ecological concepts in explaining how diverse organisms coexist and how resources such as activity time, location, and prey differ from those of other species. In the case of snakes, niche partitioning of prey resources has been considered the major factor enabling the coexistence of multiple species, although the importance of time and location of activity has also been indicated. Nevertheless, there have been no comprehensive studies on the niche partitioning of the three significant resources (time, habitat, and diet) of terrestrial snakes.

In this investigation, the researchers designated Sado Island, which has the largest number of snake species among any Japanese island, except for the subtropical Ryukyu Archipelago, as the study site and conducted a 5-year survey to determine when, where, and how seven species of snakes [Euprepiophis conspicillata (Japanese forest rat snake), Elaphe climacophora (Japanese rat snake), Elaphe quadrivirgata (Japanese striped snake), Gloydius blomhoffii (Japanese pit viper), Hebius vibakari (Japanese odd-scaled snake), Lycodon orientalis (Oriental odd-tooth snake), and Rhabdophis tigrinus (tiger keelback snake)] live and what they feed on.

Researchers identified niche complementarity among species with considerable overlap in food resources, reducing the overlap in habitat, time of activity, and season.

This study empirically revealed that terrestrial snakes coexist through “multidimensional niche partitioning,” in which a high overlap in one niche dimension should be compensated by a low overlap in at least one of the other niche dimensions. These results indicate the need to protect different types of resources to conserve snakes, which are facing a decline worldwide.

Obesity has only been officially recognized as a disease in Germany since 2020, despite the fact that it has long been known to cause a number of illnesses, including diabetes, heart attacks, and even cancer. The World Health Organization has already declared obesity to be an epidemic, affecting over one billion individuals globally and almost 16 million in Germany alone. A body mass index of 30 or more is considered obese, and a poor diet and insufficient exercise are frequently cited as the causes of this chronic illness. However, the mechanisms in the body that lead to obesity and cause the disease are more complex.

Obesity and the role of insulin in the brain

Unhealthy body fat distribution and chronic weight gain are linked to the brain’s sensitivity to insulin. What specific functions does insulin perform in the brain, and how does it affect individuals of normal weight? In their study, Prof. Dr. Stephanie Kullmann and her colleagues at the Tübingen University Hospital for Diabetology, Endocrinology, and Nephrology found the answer to this query. “Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” says Prof. Kullmann, the study’s leader. In a healthy state, insulin has an appetite-suppressing effect in the brain. However, in people with obesity in particular, insulin no longer regulates eating behavior properly, resulting in insulin resistance. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity,” says Ms. Kullmann. “This effect can even be observed one week after returning to a balanced diet,” she adds. She is also deputy head of the Metabolic Neuroimaging department at the DZD partner Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen.

Focus on the brain

Prof. Dr. Andreas Birkenfeld, Medical Director of Internal Medicine IV, Director of the IDM and DZD Board Member, and the study’s final author, concludes, “We assume that the brain’s insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases.” He urges more research on how the brain contributes to the development of obesity and other metabolic illnesses in light of the current findings.

Short period with far-reaching effects

29 male volunteers of average weight participated in the study and were split into two groups. For five days in a row, the first group had to supplement their regular diet with 1500 kcal from highly processed, high-calorie snacks. The extra calories were not consumed by the control group. Both groups underwent two separate examinations following an initial evaluation. One examination was conducted immediately following the five-day period, and another was conducted seven days after the first group had resumed their regular diet. The researchers used magnetic resonance imaging (MRI) to look at the liver’s fat content and the brain’s insulin sensitivity. Not only did the fat content of the liver of the first group increase significantly after five days of increased calorie intake. Surprisingly, the significantly lower insulin sensitivity in the brain compared to the control group also persisted one week after returning to a normal diet. This effect had previously only been observed in obese people.

The study, which examined 121 babies aged three to twelve months in Accra, the capital of Ghana, demonstrates a remarkable variety of language input in the early months of life. The children are regularly exposed to two to six languages. Strikingly, the number of caregivers the children have also ranges between two and six, and babies who have more adults in their daily lives who regularly take care of them also hear more different languages. In Ghana, families often live in so-called “compound buildings,” where many everyday interactions take place in the courtyard, where family, neighbors and other relatives play an important role in the lives of children.

“The idea that a child learns only one particular language from a single caregiver, as is often assumed in Western cultures, does not apply to these communities. Rather, children are surrounded by a rich spectrum of linguistic inputs from the very beginning,” says Paul O. Omane, the first author of the study. “The majority of studies on children’s language acquisition have been conducted in Western industrialized nations, which is why they often focus on a rather narrow conception of multilingualism. Our research shows that other societies show a much more vibrant multilingual environment,” the study’s lead researcher, Prof. Dr. Natalie Boll-Avetisyan adds.

A key finding of the study is the distinction between direct and indirect language input. While English is primarily acquired through indirect channels such as television and official communication, children receive most of the local languages (such as Akan, Ga and Ewe) through direct contact with their caregivers. Accordingly, the proportion of direct input is higher in the local languages than in English, which is predominantly present as indirect input.

It is often emphasized how important direct language contact is for language acquisition,” Natalie Boll-Avetisyan says. “However, our results suggest that indirect input — especially through media and official communication — also plays an essential role in the children’s daily lives, particularly in urban contexts.”

As a result of their empirical study, the researchers call for a broader view in language research. The common assumptions do not reflect the diversity and complexity found in other cultural contexts such as Ghana. The study makes it clear that it is not only the number of languages a child hears, but also the diversity of people and the different forms of input that have a decisive influence on language acquisition. “Our research shows that for many children, a multilingual environment is a dynamic, vibrant reality from the very beginning. Multilingualism is not just a bonus, but a fundamental part of children’s identity and social structure,” the researcher says.