"If this receptor is impaired by genetic changes, mice show signs of loss of bone density at an early age - similar to osteoporosis in humans. Using the substance AP503, which was only recently identified via a computer-assisted screen as a stimulator of GPR133, we were able to significantly increase bone strength in both healthy and osteoporotic mice," explains Professor Ines Liebscher, lead investigator of the study from the Rudolf Schönheimer Institute of Biochemistry at the Faculty of Medicine.

In bone tissue, GPR133 is activated through the interaction of neighboring bone cells and mechanical strain. This triggers a signal that stimulates bone-forming cells (osteoblasts) and inhibits bone-resorbing cells (osteoclasts). The result: stronger, more resilient bones. The new active substance AP503 can mimic this natural activation. In the future, it could be used both to further strengthen healthy bones and to rebuild weakened ones - for instance, in cases of osteoporosis in women going through menopause.

Great potential for an aging population

In an earlier study, researchers at Leipzig University had already found that activation with AP503 also strengthens skeletal muscle. "The newly demonstrated parallel strengthening of bone once again highlights the great potential this receptor holds for medical applications in an aging population," says Dr Juliane Lehmann, lead author of the study and a researcher at the Rudolf Schönheimer Institute of Biochemistry. The Leipzig research team is already working on several follow-up projects to explore the use of AP503 in various diseases and to further investigate the role of GPR133 in the body.

Background

For more than ten years, the study of adhesion G protein-coupled receptors has been a key focus at Leipzig University within Collaborative Research Centre 1423, Structural Dynamics of GPCR Activation and Signaling. Internationally, Leipzig is regarded as a leading center in this field of research.

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In a new study, which is published in PNAS, experts discovered that older people produce a glycosylated protein called apoplipoprotein D (ApoD), which is involved in lipid metabolism and inflammation, at much higher levels than in younger people. This has the effect of reducing the patient's ability to resist virus infection, resulting in a more serious disease outcome.

The team established that highly elevated ApoD production with age in the lung drives extensive tissue damage during infection to reduce the protective antiviral type I interferon response.

The research was an international collaboration led by scientists from the China Agricultural University, University of Notttingham, Institute of Microbiology (Chinese Academy of Sciences), National Institute for Viral Disease Control and Prevention (Chinese Centre for Disease Control and Prevention) and the University of Edinburgh.

"Aging is a leading risk factor in influenza-related deaths. Furthermore, the global population is aging at an unprecedented rate in human history, posing major issues for healthcare and the economy. So we need to find out why older patients often suffer more severely from influenza virus infection," says Professor Kin-Chow Chang from the School of Veterinary Medicine and Science at the University of Nottingham, and co-author on the paper.

In this new study, the team investigated the mechanisms behind increased severity of influenza virus infection with age using an aging-mouse model and appropriate donor human tissue sections.

They identified ApoD as an age-related cell factor that impairs the activation of the immune system's antiviral response to influenza virus infection by causing extensive breakdown of mitochondria (mitophagy) resulting in greater production of virus and lung damage during infection. Mitochondria are essential for cellular production of energy and for induction of protective interferons.

ApoD is therefore a target for therapeutic intervention to protect against severe influenza virus infection in the elderly which would have a major impact on reducing morbidity and mortality in the aging population.

Professor Chang, added: "There is now an exciting opportunity to therapeutically ameliorate disease severity of the elderly from influenza virus infection by the inhibitory targeting of ApoD."

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The scientists' new study in Proceedings of the National Academy of Sciences (PNAS) reveals how a partnership between algae and bacteria works like nature's clean-nitrogen machine, turning nitrogen from the air into food that fuels river ecosystems without fertilizers or pollution. The hidden nutrient factory boosts populations of aquatic insects, which young salmon rely on for growth and survival.

At the heart of the scientists' discovery is a type of diatom -- a single-celled aquatic plant in a glass-like shell -- called Epithemia. The golden-brown diatom, smaller than a grain of table salt and approximately the width of a human hair, plays a massive role in keeping rivers productive. Inside each diatom live bacterial partners housed within the cell called diazoplasts -- tiny nitrogen-fixing compartments that transform air into plant food. The diatom Epithemia captures sunlight and makes sugar, which the diazoplast uses to turn atmospheric nitrogen into a nutrient form. In return, the diazoplast provides nitrogen that helps the diatom keep photosynthesizing.

"This is nature's version of a clean nutrient pipeline, from sunlight to fish, without the runoff that creates harmful algal blooms," said Jane Marks, biology professor at Northern Arizona University and lead author of the study.

By late summer, Marks said, strands of the green alga Cladophora are draped with rusty-red Epithemia along the Eel River. At this stage, the algae-bacteria duos supply up to 90% of the new nitrogen entering the river's food web, giving insect grazers the fuel they need and powering salmon from the bottom up.

"Healthy rivers don't just happen -- they're maintained by ecological interactions, like this partnership," said Mary Power, co-author of the study and faculty director of UC Berkeley's Angelo Coast Range Reserve, where the field study took place. "When native species thrive in healthy food webs, rivers deliver clean water, wildlife and essential support for fishing and outdoor communities."

Using advanced imaging, the research team watched the partners trade life's essentials in a perfect loop: The diatom used sunlight and carbon dioxide to make sugar and share it with the bacterium, which then used the sugar to turn nitrogen from the air into plant food. That nitrogen helped the diatom make even more sugar, because the key enzymes of photosynthesis need lots of nitrogen.

"It's like a handshake deal: Both sides benefit, and the entire river thrives," said Mike Zampini, a postdoctoral researcher at NAU and the study's isotope tracing lead. "The result is a beautifully efficient cycle of energy and nutrients."

This partnership isn't unique to the Eel River. Epithemia and similar diatom-diazoplast teams live in rivers, lakes and oceans across the world, often in places where nitrogen is scarce. That means they may be quietly boosting productivity in many other ecosystems.

Beyond its role in nature, this clean and efficient nutrient exchange could inspire new technologies such as more efficient biofuels, natural fertilizers that don't pollute or even crop plants engineered to make their own nitrogen, cutting costs for farmers while reducing environmental impacts.

When nature engineers solutions this elegant, Marks said, it reminds us what's possible when people, places and discovery come together.

Other researchers involved in the study included NAU faculty Bruce Hungate and Egbert Schwartz, staff members Michael Wulf and Victor Leshyk and graduate students Raina Fitzpatrick and Saeed Kariunga; University of Alabama professor Steven Thomas and graduate student Augustine Sitati; and Lawrence Livermore National Laboratory researchers Ty Samo, Peter Weber, Christina Ramon and Jennifer Pett-Ridge. The research was funded in part by a grant from the National Science Foundation's Rules of Life/Microbiome program (#2125088). Research at Lawrence Livermore National Labs was conducted under U.S. Department of Energy Contract DE-AC52-07NA27344.