As the researchers described in Cell Reports on April 12, 2022, the new type of salivary gland cell called “ionocyte” that works to maintain healthy concentrations of charged molecules — ions — of potassium, calcium, chlorine, and other electrolytes in saliva. The scientists also found that this type of ionocyte secretes a key growth factor (fibroblast growth factor 10, or FGF10), suggesting that it has a further role in the repair of salivary glands after injury.

“These are unique cells, and we hope that by studying them we can develop better treatments for the many medical conditions that affect salivary glands and related glands such as tear glands,” says study co-senior author Helen Makarenkova, PhD, associate professor in the Department of Molecular Medicine at Scripps Research.

Salivary glands produce saliva, which makes it much easier for animals to swallow food. Saliva also contains enzymes that assist in digestion, antibodies and other immune elements to protect against infection, and finely tuned concentrations of different ions to maintain the overall health of teeth and oral tissues. Salivary glands can be damaged by cancer-related radiation therapy in the head and neck region and other medical conditions including autoimmune disorders.

“Each year, millions of Americans are diagnosed with dry mouth conditions, whose precise causes are often unclear,” says study co-first author Olivier Mauduit, PhD, a postdoctoral research associate in the Makarenkova lab.

The team, together with co-senior author Matthew Hoffman, PhD, of the National Institute of Dental and Craniofacial Research, focused first on a growth factor protein called FGF10, which is important for the early development of salivary glands, and is suspected to have a maintenance and repair function in adult salivary glands. The scientists’ aim was to discover the cell type that produces FGF10 in adult salivary glands.

The team analyzed large single cell atlases of mouse gene activity, and isolated FGF10-expressing cells for in-depth gene expression analysis. In this way, they found that while mesenchymal cells called fibroblasts produce FGF10 in very young mice, a very different cell type — a type of salivary duct-lining epithelial cell — takes over production starting in the second week of life.

The researchers showed that this FGF10-producing epithelial cell has molecular markers indicating that it is an ionocyte, an evolutionarily ancient cell type that maintains proper levels of ions and related molecules in local tissues.

Among the products of this ionocyte, they observed, is the cystic fibrosis transmembrane conductance regulator protein (CFTR). This protein is best known as the cause of the lung disease cystic fibrosis when it is absent in lungs through inherited mutation. However, it is also known to have an important role in salivary and tear glands, where its deficiency contributes to a common, inflammatory, dry-mouth/eye syndrome called Sjögren’s syndrome. The identification of the cell type that produces CFTR in the adult salivary gland might thus lead to better therapies for this syndrome, the researchers said.

The researchers noted too that this newly identified ionocyte’s FGF10-producing function makes it unique among ionocytes.

“The fact that this cell is the producer of FGF10 in adult salivary glands suggests that it could have a big role in gland maintenance and repair after injury,” says study co-author Vanessa Delcroix, PhD, a postdoctoral researcher in the Makarenkova laboratory.

Although their initial analyses concerned mouse cells, the researchers found evidence of very similar salivary gland ionocytes in a protein atlas of human tissues.

The researchers now are following up with further studies, including in human cells. Their hope is that a better understanding of how these FGF10-making ionocytes work in the adult salivary gland will pave the way for effective therapies for conditions affecting salivary glands as well as tear glands, given the many similarities between the two.

Support for the research included grants from the National Eye Institute (5R01EY026202, 5R01EY028983) and the National Institute of Dental and Craniofacial Research (R01DE031044).

Concrete, asphalt, glass, electronic chips: sand has many applications. Composed of small mineral particles, this granular material comes from sensitive dynamic environments such as seas, beaches, lakes and rivers or, from static land-based environments such as ancient river deposits and rock quarries. It is estimated that 50 billion tons of sand are used each year. Over the past two decades demand has tripled primarily due to urbanisation and population growth, a trend which is expected to continue with aggregates use reaching beyond 50 Bt per year by 2030.

In addition to the risks of local shortages, the extraction of such a volume of sand has environmental and societal consequences. For example, it is leading to erosion in river banks, which significantly increases the risk of flooding. In some countries, sand mining has caused loss of livelihoods in communities.

Two sustainability challenges with one solution

Researchers from the University of Geneva (UNIGE) and from the Sustainable Minerals Institute at the University of Queensland (UQ), Australia, have researched the potential of a viable alternative to naturally occurring sand. This material, presented in a recent report published by the two universities, has been coined ”ore-sand”.

UNIGE’s Adjunct Professor at Department F.-A. Forel for environmental and aquatic sciences of the Faculty of Science, Pascal Peduzzi said that “ore-sand has the largest potential in volume for reducing the amount of sand taken in the natural environment. By using what has been so far considered as ”left over” material, the project gives an important impetus towards a more circular economy.”

The production of ore-sand can help reduce the production of mineral mining waste and thus the further build-up of mine tailings. Mineral wastes from the mining of ores currently represents the largest waste stream on the planet, estimated between 30-60 billion tonnes per year. These residues come from crushing operations to extract certain metals from the rock.

SMI’s Development Minerals Program Leader Professor Daniel Franks said ore-sand has the potential to address two global sustainability challenges simultaneously. “Separating and repurposing these sand-like materials before they are added to the waste stream would not only significantly reduce the volume of waste being generated but could also create a responsible source of sand.”

Reduction of carbon emissions

The 12-month study independently sampled and investigated sand produced from iron ore mining, pioneered by Vale S.A in Brazil, which has previously experienced tailings dam failures. After an analysis of the chemical properties and some refining operations, the researchers were able to demonstrate that part of the material stream which would otherwise end up as mining residues could be used as a substitute for construction and industrial sand, in the same way as recycled concrete and steel slag. “If these results can be replicated with other types of mineral ores there is potential for major reductions in global mine tailings.”

“By mapping mining locations worldwide and modelling global sand consumption, we discovered that almost a third of mine sites can find at least some demand for ore-sand within a 50 km range. This could contribute to at least 10% reduction in the volume of tailings generation at each site. Simultaneously, almost half of the global sand market (by volume) could find a local source of ore-sand. For example, ore-sand could potentially substitute 1 billion metric tons of sand demand in China,” explains Daniel Franks.

In addition, the life cycle assessment of ore-sand, based on the Vale case, shows that substituting naturally sourced sand with ore-sand could potentially lead to net reductions in carbon emissions during sand production. The carbon emissions by transport is however a key consideration.

A benefit for mining companies

“Considering the co-production of ore-sand is a significant advantage for mining companies: it reduces the large tailings which hinder operational mining activities, while at the same time can generate additional revenues. Ore-sand is a step towards a “no tailings mine”, explains Pascal Peduzzi. Developing countries have fewer options for using recycled aggregate materials, given their more recent infrastructure. However, many have mining operations that can generate ore-sand as a by-product.”

Some of the next steps are to collaborate with aggregate market players to demonstrate this substitute material’s ease-of-use, performance and sourcing process. Findings from the study were presented at the 5th United Nations Environment Assembly. A new UNEA resolution (UNEP/EA5/L18/REV.1) on ”Environmental aspects of minerals and metals management” calls for strengthened scientific, technical and policy knowledge with regard to sand to support global policies and action regarding its environmentally sound extraction and use.

Citation: Golev, A., Gallagher, L., Vander Velpen, A., Lynggaard, J.R., Friot, D., Stringer, M., Chuah, S., Arbelaez-Ruiz, D., Mazzinghy, D., Moura, L., Peduzzi, P., Franks, D.M. (2022). Ore-sand: A potential new solution to the mine tailings and global sand sustainability crises. Final Report. Version 1.4 (March 2022). The University of Queensland & University of Geneva.

As the ever-evolving SARS-CoV-2 virus begins to evade once promising treatments, such as monoclonal antibody therapies, researchers have become more interested in these “decoy” nanoparticles. Mimicking regular cells, decoy nanoparticles soak up viruses like a sponge, inhibiting them from infecting the rest of the body.

In a new study, Northwestern University synthetic biologists set out to elucidate the design rules needed make decoy nanoparticles effective and resistant to viral escape. After designing and testing various iterations, the researchers identified a broad set of decoys — all manufacturable using different methods — that were incredibly effective against the original virus as well as mutant variants.

In fact, decoy nanoparticles were up to 50 times more effective at inhibiting naturally occurring viral mutants, compared to traditional, protein-based inhibitor drugs. When tested against a viral mutant designed to resist such treatments, decoy nanoparticles were up to 1,500 times more effective at inhibiting infection.

Although much more research and clinical evaluations are needed, the researchers believe decoy nanoparticle infusions someday could potentially be used to treat patients with severe or prolonged viral infections.

The study was published late last week (April 7) in the journal Small. In the paper, the team tested decoy nanoparticles against the parent SARS-CoV-2 virus and five variants (including beta, delta, delta-plus and lambda) in a cellular culture.

“We showed that decoy nanoparticles are effective inhibitors of all these different viral variants,” said Northwestern’s Joshua Leonard, co-senior author of the study. “Even variants that escape other drugs did not escape our decoy nanoparticles.”

“As we were conducting the study, different variants kept popping up around the world,” added Northwestern’s Neha Kamat, co-senior author of the study. “We kept testing our decoys against the new variants, and they just kept working. It’s very effective.”

Leonard is an associate professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering. Kamat is an assistant professor of biomedical engineering in McCormick. Both are key members of Northwestern’s Center for Synthetic Biology.

‘Evolutionary rock and a hard place’

As the SARS-CoV-2 virus has mutated to create new variants, some treatments have become less effective in fighting the ever-evolving virus. Just last month, the U.S. Food and Drug Administration (FDA) paused several monoclonal antibody treatments, for example, due to their failure against the BA.2 omicron subvariant.

But even where treatments fail, the decoy nanoparticles in the new study never lost effectiveness. Leonard said this is because the decoys put SARS-CoV-2 “between an evolutionary rock and a hard place.”

SARS-CoV-2 infects human cells by binding its infamous spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. A protein on the surface of cells, ACE2 provides an entry point for the virus.

To design decoy nanoparticles, the Northwestern team used nanosized particles (extracellular vesicles) naturally released from all cell types. They engineered cells producing these particles to overexpress the gene for ACE2, leading to many ACE2 receptors on the particles’ surfaces. When the virus came into contact with the decoy, it bonded tightly to these receptors rather than to real cells, rendering the virus unable to infect cells.

“For the virus to get into a cell, it has to bind to the ACE2 receptor,” Leonard said. “Decoy nanoparticles present an evolutionary challenge for SARS-CoV-2. The virus would have to come up with an entirely different way to enter cells in order to avoid the need to use ACE2 receptors. There is no obvious evolutionary escape route.”

Future benefits

In addition to being effective against drug-resistant viruses, decoy nanoparticles come with several other benefits. Because they are biological (rather than synthetic) materials, the nanoparticles are less likely to elicit an immune response, which causes inflammation and can interfere with the drug’s efficacy. They also exhibit low toxicity, making them particularly well-suited for use in sustained or repeated administration for treating severely ill patients.

When the COVID-19 pandemic began, researchers and clinicians experienced an unnerving gap between discovering the virus and developing new drugs to treat it. For the next pandemic, decoy nanoparticles could provide a quick, effective treatment before vaccines are developed.

“The decoy strategy is one of the most immediate things you can try,” Leonard said. “As soon as you know the receptor that the virus uses, you can start building decoy particles with those receptors. We could potentially fast-track an approach like this to reduce severe illness and death in the crucial early stages of future viral pandemics.”

The study, “Elucidating design principles for engineering cell-derived vesicles to inhibit SARS-CoV-2 infection,” was supported by the National Science Foundation (grant numbers 1844219 and 1844336) and a gift from Kairos Ventures.

Study results also pave the way for new potential therapeutic targets to rejuvenate the immune system in older adults and thereby reduce their risk of infectious disease.

“Through this study, we have gained a new understanding of why older adults are more susceptible to infectious diseases, which will enable us to identify potential new treatments,” said senior author Michael Demetriou, MD, PhD, a professor of neurology at the UCI School of Medicine and chief of the Division of Multiple Sclerosis and Neuroimmunology at UCI. First author and assistant professor in the UCI Department of Pathology, Haik Mkhikian, MD, PhD, added, “We’ve identified a potential fountain of youth for the immune system.”

The study, titled, “Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching,” was published in Nature Aging.

T cell immunity declines with aging, thereby increasing severity and mortality from infectious disease. T cells are the quarterback of the immune system and coordinate immune responses to fight off infections. The addition of complex and branched carbohydrate chains (‘glycans’) to proteins suppresses T cells function.

In this study, researchers show that the branched glycans increase with age in T cells from females more than in males due to age-associated increases in an important sugar metabolite (N-acetylglucosamine) and signaling by the T cell cytokine interleukin-7.

“Our research reveals that reversing the elevation in branched glycans rejuvenates human and mouse T cell function and reduces severity of Salmonella infection in old female mice,” said Demetriou.

Mkhikian added, “This suggests several potential novel therapeutic targets to revitalize old T cells, such as altering branched glycans or the age-triggered elevation in serum N-acetylglucosamine and IL-7 signaling.”

Aging-associated immune dysfunction, referred to as immunosenescence, contributes to increased morbidity and mortality from both infectious and neoplastic diseases in adults aged 65 years and older. In the U.S, for example, around 89 percent of annual deaths from influenza are in people at least 65?years old, despite this age group representing only around 15 percent of the nation’s population. More recently, the vulnerability of older adults to viral infections has been tragically highlighted by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Increased morbidity and mortality in older adults also occurs with common bacterial infections such as those caused by the enteric pathogen Salmonella. Furthermore, efficacy of immunizations declines with age, further increasing risk of infection in older adults. The rapidly aging population in the developed world exacerbates this issue and heightens the need for interventions that effectively target immunosenescence.

Previous studies examined transcriptome changes in highly purified aged T cell subsets. In this study, researchers analyzed T cell populations by age and sex, with results suggesting sex-specific differences that imply that effective interventions to reverse immune dysfunction in older adults may require sex-specific strategies.

The study was supported by funding from the National Institute of Allergy and Infectious Disease, the National Center for Complementary and Integrative health, The Burroughs Wellcome Fund and a predoctoral fellowship from the American heart Association.

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Warming winters may sound like a welcome change for some farmers because the change in temperature could reduce freezing stress on plants and create more ideal conditions for growing overwinter cash crops and winter cover crops. However, when looking at climate change from a cross-seasonal perspective and accounting for declining snowpack, researchers are finding that the whole picture isn’t so sunny.

Reduced snow may result in more exposure of winter crops to freeze and could mean greater risks for agricultural drought.

In a new study published in Nature Climate Change, Zhenong Jin, Ph.D., an assistant professor in the Department of Bioproducts and Biosystems Engineering at the University of Minnesota, led an international team in researching the implications that could be associated with warmer winters and declining snowpack, using winter wheat (the largest winter crop in the U.S.) as an example.

“Although the implications of changes in snow for agricultural irrigation are beginning to be understood, the consequences of such for predominantly rainfed winter crops such as winter wheat remain largely unknown. There might be risks for being overoptimistic about growing overwinter crops under climate change,” said Jin.

Researchers used panel regression, a powerful statistical method to analyze repeated observations over time, to attribute the interannual variability of winter wheat yield to multiple interactive environmental factors. These factors included cold season freezing degree days, growing degree days, rainfall and snowfall during the growing season and snow cover fraction during frozen days.

The researchers found:

• From 1999-2019, snow cover insulation weakened yield losses due to freezing stress by 22%.
• Projections show that future reduced snow cover could offset up to one-third of the yield benefit from reduced frost.

“Our study highlighted the potential freezing risk in winters with decreased snow cover, especially when seedlings were exposed to comparatively warmer conditions that caused loss of winter-hardiness, which can cause significant yield losses of winter crops,” said Peng Zhu, Ph.D., a Researcher from the Climate and Environment Sciences Laboratory of the Pierre Simon Laplace Institute, who co-led this study.

This research will help inform breeders as they consider the complex tradeoffs among warming, reduced snowpack and occasional freezing threats when developing climate-smart cultivars.

These results also highlight the necessity of improving the representation of snow associated processes in crop models to better evaluate climate change effects and adaptation potential in cropping systems.

“It is worth noting that in some cropping systems freezing stress is appreciated, since it helps farmers control pests and diseases and snow is even removed or at least made more compact by farmers to increase the freezing of the soil,” said Jin. “When data becomes available, future studies might also need to account for the influence of snow on pests and diseases to comprehensively understand what future changes in snowpack mean for the cropping system.”

Funding for this research was partially supported by the USDA National Institute of Food and Agriculture (NIFA) and the French National Research Agency.

Other members of the University of Minnesota research team include Taegon Kim and Chenxi Lin from Jin’s group and David Mulla from the Department of Soil, Water, and Climate.

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