Publisher Health

In what is believed to be a world first discovery, University of Otago researchers have found wheat gluten causes brain inflammation in mice.
The research, led by Associate Professor Alex Tups, and published in the Journal of Neuroendocrinology, may be of importance for human physiology.
“Mice are an excellent model to study human physiology. They have a very similar circulatory, reproductive, digestive, hormonal and nervous system.
“So, it is quite possible that the same inflammation we found in mice could happen in humans.”
The study investigated whether a standard diet, referred to as low fat diet (LFD), enriched with 4.5 per cent gluten (matching human average daily consumption), or a high fat diet (HFD), enriched with 4.5 per cent gluten, alters body weight, metabolic markers or central inflammation in male mice.
“Gluten, which is found in cereals such as wheat, rye and barley, makes up a major dietary component in most western nations.
“While previous studies have shown gluten promotes body mass gain and inflammation in mice in the enteric nervous system and gastrointestinal tract, we investigated the impact of gluten on the brain.”
While somewhat expectedly, the study confirmed a “moderate obesogenic effect of gluten when fed to mice exposed to a high fat diet, for the first time we can report gluten-induced hypothalamic (brain) inflammation,” Associate Professor Tups says.

Russia’s war in the Ukraine has severe consequences not only for humans, it also has detrimental effects on populations of urban and semi-urban wildlife in the attacked cities and regions. Scientists from the Ukrainian Bat Rehabilitation Center recently examined the effects of war-related damages to buildings on urban populations of one important and widespread bat species, the Common Noctule (Nyctalus noctula), in the city of Kharkiv in north-eastern Ukraine. They showed that many buildings used by bats as roosts have been destroyed and approximately 7,000 bats were killed. In addition, partially destroyed buildings have become a death trap for bats, resulting in several thousand more victims. The findings are published in the Journal of Applied Animal Ethics Research.
The mission of the Ukrainian Bat Rehabilitation Center (UBRC) is to protect, rescue and conduct long-term research on bats, with the Kharkiv region as the focus of their efforts. Kharkiv is Ukraine’s second largest city and one of the places where conflicts between Ukrainian and Russian forces have been most intense to date. UBRC director Dr Anton Vlaschenko, who is also affiliated with the Berlin-based Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), says: “Our findings suggest that 45.1% of buildings used as wintering roosts for Common Noctules were either partially damaged or completely destroyed by shellings, which may have led to the direct killing of approximately 7,000 bats.” Additionally, the war-damaged urban environment in Kharkiv has become a deadly trap for the bats during the period of autumn migration or swarming. “Bats entered the interiors of buildings through windows that were left open or broken by blast waves, resulting in entrapment,” says former Leibniz-IZW PhD student Dr Kseniia Kravchenko from the UBRC.
Windows left open by people and/or were broken by blast waves are a notable threat for migratory bats that enter the building and get trapped inside the apartments or between window frames. Some of the windows in the city are of an old double-glazed type — two frames with a space between them — and the bats end up trapped in the middle. “The issue has been known to occur in Kharkiv since the 1960s, but the war exacerbates the problem by creating ever more human-made traps for bats,” reports Vlaschenko . Before the war, UBRC scientists used to rescue up to 500 bats from such windows during the autumn bat migration. Owing to the war, the number of cases of bats trapped in partially damaged buildings and/or abandoned apartments was three times higher than in previous years. Almost all of them were Common Noctules. The team reports that they discovered 2,836 Common Noctules trapped inside buildings damaged by shelling and that approximately 30 percent of them were already dead upon discovery. Noctules flies in groups and these groups can get lost in urban structures. The size of trapped groups was clearly larger than in previous years, especially in the districts of the city most damaged by the ongoing war such as Saltivka,” says Kravchenko. During the first weeks of the full-scale war (February-March 2022) alone, almost half of the buildings known as winter roosts of Common Noctules were partially (31.4%) or fully (13.7%) damaged by Russian shelling, which may have led to the direct killing of thousands of bats.
The number of bats present in Kharkiv in 2022 was exceptional high, as Common Noctules stayed in the Kharkiv city area all autumn. The scientists also found that these bats had a larger body mass than usual. These changes might have been a consequence of the destruction of street lights and power plants in Kharkiv and most of the settlements in Ukraine since the beginning of the war. The absence of artificial light might result in more bats entering the city, as this removed any “light barrier” for nocturnal animals and facilitated a rapid recovery of night-active insect populations.
“The war created many new challenges in our lives and to those of bats, but we don’t lose focus on our mission to protect wildlife and exploit the current context to learn as much as we can on our favourite animals,” concludes Vlaschenko. The war has indeed made their working condition extremely difficult, but the team of the Ukrainian Bat Rehabilitation Center remains very active and continues to save bats, gather data, run workshops and collaborate with many scientists and institutes in Ukraine and beyond, such as with the Leibniz-IZW.

People with albinism often have poor vision. A new study from the Netherlands Institute for Neuroscience reveals the underlying cause.
In Europe, albinism occurs in 1 in 20,000 individuals. However, in some populations, it is much more common, affecting 1 in 1,000 people. People with albinism lack pigment and frequently have poor eyesight. For example, they may see at a distance of 20 meters what someone with pigment sees at 80 meters. But what exactly causes this?
One of the causes is the spontaneous back-and-forth movement of the eye, called ‘pendular nystagmus.’ This phenomenon not only makes seeing difficult but also hinders social eye contact. Treatment sometimes involves medications or surgery on the eye muscles, but these methods have unpleasant side effects and are not fully effective. Understanding the underlying mechanisms behind this condition is essential for developing alternative treatment strategies.
Moving train
Pendular nystagmus resembles the eye movements people make when looking outside while riding a moving train: the eyes automatically move along with the moving landscape and then spring back to the resting position. Nerve cells in a small brain area (known as the nucleus of the optic tract) selectively respond to this movement and become active. In healthy individuals, this activity leads to the tightening of the eye muscles to stabilize the image. However, in albinism, this process works a bit differently.
Jorrit Montijn, Valentina Rugiccini and their colleagues, under the supervision of Alexander Heimel, have now demonstrated in albino mice that the cells in this brain area are no longer selective for the direction of image movement. As a result, the image cannot stabilize, leading to the condition of pendular nystagmus. Currently, surgery of this brain area is not possible, but the research provides hope that in the future, pendular nystagmus can be reduced through manipulation of activity in this brain region.
Ruling out cortex
Jorrit Montijn: “We show that the nucleus of the optic tract might be the source of the problem. Previous research already suggested that this area is involved in eye movements, but it could not be ruled out that (also) other areas, such as the cortex, cause pendular nystagmus. By simultaneously measuring both the cortex and the nucleus of the optic tract in the same mice, we were able to eliminate this question.”
“We now know that there is something wrong with this area, but we still don’t know what can be done about it. The next steps would be to translate this into practice. One possible option could be Deep Brain Stimulation of the area, but this still needs to be tested, and it is not known if it has an effect. Another option is perhaps surgery or even gene therapy in the future. It is now up to more clinically oriented scientists to investigate this.”
The study was made possible by a donation from Mrs. Van Hessen-Israels for research on the consequences of albinism.

It has been known for several years that the diagnosis “multiple sclerosis” conceals a whole range of different illnesses, each requiring customized treatment. Researchers at the University of Basel and the University Hospital of Basel have now described a possible new MS-like disease and explained how to diagnose it.
Multiple sclerosis (MS) is characterized by areas of inflammation in the central nervous system. The immune system attacks the body’s own structures and destroys the covering of nerve cells, known as the myelin sheath. The picture research has painted of the illness is somewhat more complicated, however. It can cause a variety of neurological symptoms, like paresthesia and paralysis of the limbs, which progressively or abruptly worsen. Which parts of the nervous system are affected varies substantially between individuals. A treatment may work for some patients — but make the condition worse in others.
“There’s a huge amount of diversity in how inflammatory autoimmune diseases of the central nervous system like multiple sclerosis present,” explains Professor Anne-Katrin Pröbstel of the University of Basel and University Hospital Basel. Researchers have been gradually discovering the key distinctive features of “atypical” cases of MS for the past ten years. A few of these autoimmune diseases have been given different names to better distinguish them from MS even though they also destroy the myelin sheath. Victims of these diseases often have inflammation in their spinal cords or optic nerves.
In a study of roughly 1,300 patients, Pröbstel’s team has now discovered a biomarker that may make it possible to differentiate another MS-like illness from the others. The researchers have reported their findings in the journal JAMA Neurology.
Antibodies as biomarkers
The team discovered a specific antibody, a type of immunoglobulin A (IgA), in one group of patients. The antibody attacks a component of the myelin sheath called “MOG” (which stands for “myelin oligodendrocyte glycoprotein”). IgA antibodies are typically responsible for protecting mucous membranes.
The precise role of MOG-IgA in this autoimmune disease remains unclear, however. “Victims experience inflammation particularly in their spinal cords and brain stems,” Pröbstel explains. This group of patients was missing other typical biomarkers related to MS or similar diseases.
Next, the researchers want to decipher the role of MOG-IgA and the clinical characteristics arising from it in more detail. “By distinguishing between myelin-destroying autoimmune diseases that were previously all called MS, we’re taking an important step towards a better understanding of the causes of these illnesses and towards individualized treatments,” says the neurologist. Ultimately, the researchers hope to discover what treatments are most effective under what conditions.
About the project
The study was conducted in collaboration with the Universidade de São Paulo in Brazil and several German universities (Charité Berlin, Heinrich Heine University Düsseldorf, Ruhr University Bochum). The research team from the Departments of Biomedicine and Clinical Research of the University of Basel, the Department of Neurology at the University Hospital, and the Research Center for Clinical Neuroimmunology, which is affiliated with both institutions, received funding for the study from the University Hospital of Basel’s Propatient Foundation, the Goldschmidt-Jacobson Foundation, the Fondation Pierre Mercier pour la Science, the National Multiple Sclerosis Society and the Swiss National Science Foundation. The two lead authors received grants from the European Committee for Treatment and Research in Multiple Sclerosis Clinical Fellowship, as well as the Swiss Government Excellence Scholarship (Ana Beatriz A.G.R. Gomes) and the Trygve Tellefsens Legat Scholarship (Laila Kulsvehagen).

Some HIV-1 carriers who have received an early antiretroviral treatment during several years are able to control the virus for a long term after treatment interruption. However, the mechanisms enabling this post-treatment control have not been fully elucidated. For the first time, teams of scientists from the Institut Pasteur, Inserm and the Paris Public Hospital Network (AP-HP), supported by ANRS | Emerging Infectious Diseases, have investigated and revealed how neutralizing antibodies, including those described as broadly neutralizing, contribute to virus control. These key findings were published in the journal Cell Host & Microbe on July 10, 2023. A clinical trial involving the use of broadly neutralizing antibodies should begin in France before the end of 2023.
“Post-treatment controllers” is the term used to describe the rare HIV-1 carriers who, having initiated treatment early and maintained it for several years, are able to control the virus for years after that the treatment has been discontinued. These individuals were identified several years ago in part through the VISCONTI[1] study, which assembled the largest cohort of long-term post-treatment controllers in France. Although the mechanisms of viral control enabling the long-term remission from HIV-1 infection without antiretroviral therapy have not been fully elucidated, the identification of these cases provides a unique opportunity to refine our understanding of the factors associated to HIV-1 infection control.
A study conducted by the Institut Pasteur’s Humoral Immunology Unit led by Dr. Hugo Mouquet in collaboration with the team led by Dr. Asier Sáez-Cirión, Head of the Institut Pasteur’s Viral Reservoirs and Immune Control Unit, is now contributing to efforts to describe these mechanisms in more detail. Asier Saéz-Cirión explains: “Our investigation published in 2020 on the immune response in post-treatment controllers marked a major first step in demonstrating an effective and robust antibody response to HIV-1 in some of these individuals, which may contribute to this control[2]. This knowledge has now been further advanced by our new study. By investigating the role of antibodies in a specific “post-treatment controller” case with particularly high serum levels of broadly neutralizing antibodies, we discovered that remission was probably linked to the activity of this type of antibodies.”
Hugo Mouquet describes the discovery: “Our study describes for the first time in a post-treatment controller a family of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope protein, of which the antibody EPTC112 is one of the most active member.”
The antibody EPTC112 neutralizes about a third of the 200 viral variants of HIV-1[3] tested in vitro and is able to induce the elimination of infected cells in the presence of natural killer (NK) cells, the immune cells eliminating abnormal cells in the body.
This study therefore provides important insights on how neutralizing antibodies modify the course of HIV-1 infection in this individual from the VISCONTI cohort. Although the HIV-1 virus circulating in this subject was found to be resistant to EPTC112 neutralization due to mutations in the region targeted by this antibody, it was effectively neutralized by other antibody populations isolated from the blood of the individual. Hence, the study suggests that neutralizing antibodies from the EPTC112 family impose a selective pressure on the HIV-1 virus. Although the virus escaped the action of these bNAbs, it remained susceptible to the neutralization by other anti-HIV-1 antibodies produced in this individual. This observation suggests the existence of a cooperation between the various populations of neutralizing antibodies.
“The fact that we discovered a potential link between the production of neutralizing antibodies, including bNAbs, and the HIV-1 control is exciting to better understand the underlying mechanisms of viral control, particularly by studying additional post-treatment controllers with similar profiles. Indeed, we wish to continue investigating on a short term whether the antibody responses in other ‘post-treatment’ controllers also contribute to long-term remission from the infection,” explains Hugo Mouquet.

Overly active immune cells are often behind lung damage in diseases such as Covid-19. Researchers at the Technical University of Munich (TUM) have developed an RNA agent for a lung spray that slows the activity of these cells, known as macrophages. A new, sugar-based transport mechanism is especially effective in bringing the therapeutic to its target.
The team led by Stefan Engelhardt, Professor of Pharmacology and Toxicology, has developed an RNA-based active ingredient called RCS-21 to prevent severe lung inflammation and fibrosis, i.e. scarring of the lung tissue, for example in SARS-CoV2 infections.
In the cell, RCS-21 stops the activity of the molecule microRNA 21. This nucleic acid, which Engelhardt and his team have been researching for a long time, is one of the triggers for the excessive activity of macrophages in severe lung infections.
Drug docks onto sugar receptors
In the scientific journal Nature Communications, the team now describes how the active substance RCS-21 is delivered to its target particularly effective via an inhaler. To do this, the researchers took advantage of a special feature of macrophages. These scavenger cells are also present in large numbers in the healthy lung. There, they perform the important task of destroying bacteria and fungal spores as quickly as possible. The macrophages identify their targets among other things based on complex sugar molecules on the surface of the invaders. “We have determined in single cell analyses that the corresponding sugar receptors are, on the one hand, among the most common receptors on macrophages,” says Stefan Engelhardt. “On the other hand, the receptors are, in a sense, a unique feature of macrophages — they hardly occur anywhere else.”
Therefore team coupled its active ingredient to a sugar molecule, or more precisely: to trimannose. This approach had so far only been pursued with chemically less complex active ingredients. Studies with mice produced clear results. “When the drug was administered as a spray, macrophages took up the active ingredient significantly better than without sugar molecules. In contrast, other cell types even outright exclude the molecules,” says Christina Beck, first author of the article together with Deepak Ramanujam.
Active substance successfully tested
In experiments with mice, RCS-21 ensured that microRNA 21 was reduced by more than half compared to control animals. Fibrosis and inflammation were also significantly reduced after treatment. Increased microRNA-21 activity was also stopped by treatment with RCS-21 in samples of human lung tissue infected with the SARS-CoV-2 coronavirus in the laboratory.

Often referred to as the “powerhouses of the cell,” mitochondria are well known for their role as energy suppliers, but these organelles are also critical for maintaining our overall health.Mitochondrial stress is associated with aging and age-related diseases, including neurodegeneration, but there has been a limited understanding of the molecular mechanisms behind this mitochondrial stress signaling. Now, a study by Scripps Research scientists has revealed an important step in this process.
The new study, published August 7, 2023, in the journal Nature Structural & Molecular Biology, shows how a mitochondrial protein structure is necessary to activate the cell’s integrated stress response (ISR) — a critical pathway that helps our cells maintain health. The researchers believe this mitochondrial structure, made up of a protein called DELE1, could serve as a target for future therapeutics for age-related diseases.
“Understanding the molecular details of this signaling pathway could help us potentially develop treatments for a range of diseases, such as neurodegenerative diseases, cancer and heart disease,” says first author Jie Yang, PhD, a postdoctoral fellow in the lab of Gabriel Lander at Scripps Research.
In order to maintain cellular function and health, mitochondria must continually sense and respond to stressors, such as viral infections and iron deficiency. However, their ability to do so decreases as people age.
“Just like every other part of our body, mitochondria age and become slightly less productive,” says co-author Kelsey Baron, a graduate student in the lab of Luke Wiseman at Scripps Research. “When you have this loss of mitochondrial productivity, your cells don’t have as much energy to fight different stressors, and many people believe that is a major trigger of neurodegeneration.”
One method by which mitochondria deal with stress is by activating the ISR. Prior studies have shown that the DELE1 protein is involved in activating this integrated stress response, but before now, little was known about the protein’s molecular structure. Characterizing DELE1’s structure is a key step towards understanding and treating diseases associated with mitochondrial stress.
The researchers focused on a fragment of DELE1 — the C terminus — that is known to be actively involved in initiating the ISR. When they isolated this fragment, they were surprised to find that it was much heavier than expected, which suggested that multiple copies of the protein fragment were binding together. Using electron microscopy, the team showed that this protein complex (or oligomer) was a highly symmetrical cylinder composed of eight identical fragments — in other words, an octamer.

Tumor cells are known to be fickle sleeper agents, often lying dormant in distant tissues for years before reactivating and forming metastasis. Numerous factors have been studied to understand why the activation occurs, from cells and molecules to other components in the so-called tissue microenvironment.
Now, an interdisciplinary Cornell team has identified a new mechanism regulating tumor growth in the skeleton, the primary site of breast cancer metastasis: mineralization of the bone matrix, a fibrous mesh of organic and inorganic components that determines the unique biochemical and biomechanical properties of our skeleton.
The team’s paper, “Bone-Matrix Mineralization Dampens Integrin-Mediated Mechanosignalling and Metastatic Progression in Breast Cancer,” published Aug. 7 in Nature Biomedical Engineering. The co-lead authors are research associate Siyoung Choi and doctoral student Matthew Whitman.
The project is the latest collaboration between co-senior authors Claudia Fischbach, the Stanley Bryer 1946 Professor of Biomedical Engineering, and Lara Estroff, the Herbert Fisk Johnson Professor of Industrial Chemistry, both in Cornell Engineering, who together have been exploring the metastatic spread of breast cancer to bone for more than a decade.
Fischbach’s lab uses biomaterials in combination with cellular and tissue engineering approaches to understand how the tissue microenvironment regulates cancer in different contexts, while Estroff’s group specializes in biomineralization – the way biological organisms control the growth of crystals in their tissues.
“We know that cancer cells behave like seeds that need the right soil to grow, and we’re very interested in how the extracellular matrix, which is basically the material in between cells that holds everything together, affects tumor growth,” Fischbach said.
During physiological mineralization, bone mineral particles are deposited in and around collagen type I fibers. This process occurs naturally and is necessary for bone health but decreases with age – for example, due to hormonal changes as seen in women undergoing menopause. It can also result from dietary changes or chemotherapy.

Researchers with the University of Oklahoma’s Natural Products Discovery Group recently published findings that indicate a novel breakthrough treatment for fungal infections.
Fungal infections are killing thousands of Americans each year, some with a morbidity rate of nearly 80%. To make matters worse, only a handful of antifungal treatments are available, and even those are becoming less effective as fungi become more resistant. However, University of Oklahoma researchers recently published findings in the Journal of Natural Products indicating that a novel breakthrough treatment may have been discovered.
“The molecule we’re excited about is called persephacin,” said Robert Cichewicz, Ph.D., principal investigator and Regents Professor in the Department of Chemistry and Biochemistry, Dodge Family College of Arts and Sciences at OU. “This antifungal discovery appears to work on a broad spectrum of infectious fungi, and it is reasonably non-toxic to human cells, which is a huge deal because many current treatments are toxic to the human body.”
The rise in fungal infections is due, in part, to the successful treatment of other diseases. As people live longer and successfully undergo treatments like chemotherapy and organ transplants, they often live with weakened immune systems. When drugs that treat arthritis and other ailments that also weaken immune systems are added to the mix, a perfect storm is created for potentially deadly fungal infections.
Cichewicz, who has been researching fungi for nearly 20 years, leads the Natural Products Discovery Group at OU. This team of researchers discovered this novel molecule and developed a unique method for testing plants for their antifungal properties.
“Fungi are found throughout the botanical world, and plants and fungi often work together. Some of these fungi kill competitors or deter insects from eating the plant,” Cichewicz said. “We hypothesized that if these plant-dwelling fungi, known as endophytes, could help the plants fight off infections by killing the invading fungi, then these molecules might also be able to protect humans and animals from fungal pathogens. As it turns out, we were right.”
The team developed a novel way to procure leaf samples using a laser device called the Fast Laser-Enabled Endophyte Trapper, or FLEET. This method helps generate samples in a sterile environment and drastically increases the number of samples that can be acquired.
“Using traditional methods, we could process roughly four to six samples per minute,” Cichewicz said. “But our FLEET system is capable of aseptically generating between 500-600 tissue specimens in 10 minutes. This allows us to rapidly screen more samples and enhances the opportunity for potential drug discoveries.”
With assistance from the Office of Technology Commercialization at the University of Oklahoma, Cichewicz was awarded a U.S. patent for using persephacin to control infectious pathogens.
“It’s taken us a long time to get to this point, but now we’re hoping to work with an industry partner to help us develop this treatment,” Cichewicz said. “Antifungal resistance keeps evolving, and this could provide a new alternative. That’s why this molecule is so exciting.”

Researchers at Kobe University discovered an entirely new and unexpected mechanism by which the immune system can get rid of cells lacking molecules that identify them as part of the self in mice. The finding, published in PNAS, has possible implications for cancer treatment.
The immune system comprises many types of cells that work together to fight off diseases. Two important types are dendritic cells and T cells. Dendritic cells are located in strategic positions throughout the body including the gut and skin, as well as in the lymph nodes, sample their environment and present small components derived from these samples on their surface. T cells check these samples and if they recognize them as foreign (or “non-self”), they will initiate an immune response, otherwise they will move on. The ability to distinguish self from non-self is therefore a key characteristic of the immune system and T cells undergo very selective training, by dendritic cells, to make sure they can make that distinction.
The cells in our body display several molecules on their surface that identify them as “self” to immune cells. One of these self-identifying molecules is CD47. It was known that if T cells lack CD47, they would be efficiently eliminated by other immune cells. However, various experiments with mice lacking CD47 failed to produce an indication of the molecular mechanism or which cells were responsible for the elimination. Now, the research group of Associate Professor SAITO Yasuyuki, Postdoctoral fellow KOMORI Satomi, and Specially Appointed Professor MATOZAKI Takashi at Kobe University, that has been working on the molecular interaction between dendritic cells and T cells and in particular on the role of CD47 in that process, tried a novel approach. Saito explains: “We generated genetically modified mice in which only T cells lack CD47. This is quite different from the conventional approach with mice that systematically lack CD47 on all cells.” This new approach enabled them to isolate the role of CD47 on T cells from other factors that might influence the interaction.
Their results, published in the journal PNAS, clearly identified dendritic cells as those killing T cells lacking CD47. Not only does this for the first time shed light on the mechanism behind the disappearance of CD47-deficient T cells, it also reveals a completely unexpected capability of dendritic cells. “This result is totally novel because it was believed that CD47-deficient cells are engulfed by a type of immune cells called ‘macrophages’ and that dendritic cells never induce cell death in other immune cells,” says Saito. The team thus found an entirely new way in which the body identifies missing-self cells, that is, cells lacking CD47 being killed directly by dendritic cells.
This finding also suggests a new line of research. Now that this new ability of dendritic cells has been discovered, is it used on other kinds of cells, too, and can it be used therapeutically? Saito says: “Our results raise the question: do dendritic cells induce cell death in other cells that lack CD47? This question is so important because this novel mechanism can be applied to the induction of cell death by modification of CD47 on target cells, such as cancer cells.”
The group has already initiated further research projects to clarify these questions and also to better understand the mechanism behind this newly-discovered capability of dendritic cells. They have also started work to verify the potential of treating cancer based on this novel finding.