Publisher Health

Australian scientists have taken the first step towards improved storage of human cells, which may lead to the safe storage of organs such as hearts and lungs.
The team’s discovery of new cryoprotective agents opens the door to many more being developed that could one day help to eliminate the need for organ transplant waiting lists. Their results are published in the Journal of Materials Chemistry B.
Cryopreservation is a process of cooling biological specimens down to very low temperatures so they can be stored for a long time. Storing cells through cryopreservation has had big benefits for the world — including boosting supplies at blood banks and assisting reproduction — but it is currently impossible to store organs and simple tissues.
The lead researcher, Dr Saffron Bryant from RMIT University, said about 60% of all donated hearts and lungs were discarded.
“We have these massive organ shortages, yet most of them just get thrown away,” she said.
“We only have hours to get an organ from a donor to a recipient. If someone’s in a car accident in Melbourne, for example, you’re limited to Melbourne and areas immediately surrounding it because the chances of getting it to the airport, even to take it to Sydney, are practically zero. There’s no way to transport organs to people overseas who desperately need them.”
About 1,850 people are on the waiting list for an organ transplant in Australia, while more than 100,000 Americans are waiting for a transplant.

James Bond’s legendary quartermaster Q provided the special agent with an endlessly array of tools and gadgets to help him accomplish his missions. Now, researchers from Japan have demonstrated equal prowess at equipping microscopic worms with a surprising arsenal of functional and protective factors.
Researchers from OsakaUniversity have revealed that tiny free-range worms called nematodes can be coated in hydrogel-based “sheaths” that can be further modified to carry functional cargo.
Nematodes are free-living, microscopic worms that typically live in the soil or other environmental niches, and in some cases can invade the human body. Anisakis simplex, a nematode that usually lives in marine environments but can colonize humans when ingested, has demonstrated an unusual predilection for cancer cells.
“A. simplex has been reported to sense cancer, potentially by detecting a cancer “odor,” and to attach to cancerous tissues,” says Wildan Mubarok, first author on the study. “This led us to ask whether it could be used to deliver anti-cancer treatments directly to cancer cells within the human body.”
To investigate this possibility, the researchers first developed a system for applying hydrogel sheaths to nematodes by dipping them in a series of solutions containing chemicals that bind together to create a gel-like layer all over their surface. This process essentially custom-fits a suit about 0.01 mm thick to the worm in about 20 minutes.
“The results were very clear,” says Shinji Sakai, senior author of the study. “The sheaths did not in any way interfere with the worms’ survival and were flexible enough to maintain the worms’ motility and natural ability to seek out attractive smells and chemical signals.”
Next, the researchers loaded the sheaths with functional molecules and found that this protected the worms from ultraviolet light or hydrogen peroxide. What’s more, the sheaths could be loaded with anti-cancer agents that the nematodes, protected but unimpeded by their hydrogel armor, could transport and deliver to kill cancer cells in vitro.
“Our findings suggest that nematodes could potentially be used to deliver functional cargo to a range of specific targets in the future,” states Mubarok. Given the adaptability of the hydrogel sheaths, this worm-based delivery system holds promise not only for delivering anti-cancer drugs to tumor cells in patients, but it also has potential applications in other fields such as delivering beneficial bacteria to plant roots.
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In a leap forward for diabetes research, Tokyo Tech researchers reveal that the ‘feel-good hormone,’ dopamine, regulates insulin secretion through a heteromeric complex of receptors, thereby providing new targets for antidiabetic medication and therapy. The study is the first to elucidate the mechanism behind dopamine’s down-regulation of insulin secretion.
Diabetes is a lifelong, chronic health condition caused by abnormalities in the body’s production and use of the hormone insulin. Research has shown that the feel-good hormone, dopamine (DA), plays a key role in how the body regulates the production of insulin. Typically, insulin is secreted by cells in the pancreas called ‘beta-cells,’ in response to glucose — a process that is aptly called ‘glucose-stimulated insulin secretion (GSIS). DA negatively regulates GSIS, leading to transient changes in the body’s levels of insulins. But the mechanism behind this regulation was unknown, until now.
Recently, a team led by researchers from Tokyo Institute of Technology (Tokyo Tech) uncovered the precise mechanism through which DA regulates insulin secretions. Using a technique called “total internal reflection fluorescence microscopy,” they were able to reveal that DA “receptors” — proteins on cells that DA can bind to — called D1 and D2, act in concert to achieve the transient regulation of insulin.
“We found that D1 receptor antagonists — drugs that block D1 receptors from activation — decreased the dopamine-mediated inhibition of insulin secretion. We also saw that overexpression of only D2 receptors on beta cells exerted an inhibitory and toxic effect and abolished insulin secretion in beta-cells. This gave us a clue to the mechanism of down-regulation,” explains Prof. Shoen Kume of Tokyo Tech, who led the study.
The research team then performed further experiments called “proximity ligation” and “Western blot assays” to study the receptors further. They found that D1 and D2 bound to each other to form a complex called a “heteromer.” When activated by DA, this heteromer transiently inhibited insulin secretion. They also saw that when D1 and D2 were co-expressed on beta-cells, the cells were able to bypass the toxic effects of D2 overexpression.
Dr. Kume says, “From these findings it can be concluded that D1 modulates D2 signaling to protect beta-cells from the harmful effects of DA. This study greatly improves our understanding of DA signaling in diabetes.”
Understanding the mechanism of DA signaling in the regulation of insulin secretion is sure to provide new therapeutic targets for the prevention, treatment, and management of diabetes.
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A research team at MedUni Vienna has discovered key mechanisms of allergy to pollen from the common weed mugwort, thereby also laying the foundation for the development of the world’s first vaccine. Mugwort (Artemisia vulgaris) poses a serious problem for allergic individuals in our latitudes from July through to September. Currently, the symptoms, which often lead to asthma, can only be treated symptomatically. The recent findings are an essential first step toward causal therapy and prevention of mugwort pollen allergy. The landmark study has now been published in the Journal of Allergy and Clinical Immunology.
In their preclinical research, the scientists started at the point of origin of mugwort pollen allergy. They discovered where and how the immunoglobulin E (IgE) type antibodies detect the major mugwort pollen allergen (Art v 1) and trigger the exaggerated immune response. They also found that distinct protein building blocks of the main mugwort pollen allergen are in such a configuration that they can be blocked by IgG (immunoglobulin G) antibodies.
These findings by the research team led by Maja Zabel and Winfried Pickl, in collaboration with Rudolf Valenta’s research team (all from MedUni Vienna’s Center for Pathophysiology, Infectiology and Immunology), created the basis for the development of a vaccine against mugwort allergy: “Our study shows how fragments of the major mugwort pollen allergen can be used for effective and safe therapy,” says study leader Winfried Pickl. “Our observations of the mode of action of the vaccine show that one of the ends of the main mugwort pollen allergen provides important docking sites for the pathogenic IgE antibodies of allergic individuals, which can be used for creating a novel vaccine,” Winfried Pickl elaborates. The first author of the study is Maja Zabel, who conducted the work during her PhD studies at the MedUni Vienna as part of the FWF-funded doctoral programme “Molecular, Cellular and Clinical Allergology, MCCA.” This programme is now part of the Danube Allergy Research Cluster (Danube ARC), which is funded by the State of Lower Austria.
Widespread in the northern hemisphere
Mugwort is widespread in the northern hemisphere, where its pollen causes discomfort and even asthma in sensitized individuals from July through to September. The only treatments available to the approximately 10% of the population who are sensitive to mugwort are limited to symptomatic relief. The current MedUni Vienna study is an internationally acclaimed first step towards causal therapy and prevention. “Next, we will use our research results to produce a synthetic vaccine that can be evaluated in a clinical trial,” explains Rudolf Valenta, outlining the next step on the path to developing an effective vaccine.
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Stem cells and progenitor cells play an important role in the renewal of multiple tissues. Professor Jyrki Heino’s research group from the University of Turku together and Professor Fiona Watt´s research group from King’s College London have discovered a molecule called embigin on the surface of epithelia progenitor cells and proven its significance to sebaceous gland function.
In biochemical experiments conducted at the University of Turku, researchers were able to demonstrate that embigin binds to the extracellular matrix protein called fibronectin that acts as adhesion molecule for cells.
“Embigin has been discovered in malignant embryonic cells decades ago. However, little has been known about how this molecule functions and what kind of role it has in the normal cells of the body,” says the first author of the article, Dr Kalle Sipilä from King’s College London.
Embigin seems to operate in the body in the same way as in a laboratory: when the researchers from King’s College London removed embigin from the stem cells of the skin by editing the mouse genome, the sebaceous gland progenitor cells detached from the extracellular matrix and began their differentiation prematurely.
“Embigin does not only help cells to adhere and differentiate punctually, but it also directs some transport proteins on the cell surface, through which precursors molecules of lipid synthesis can access the cell. This process is especially important for the sebum production to lubricate skin,” says Sipilä.
Multinational collaborations, researcher mobility, and interdisciplinary collaborations are particularly important for biomedical research.
“For example, there is top level expertise in Turku to study a protein structure-function relationship,” says Professor of Biochemistry at the University of Turku Jyrki Heino.
The interaction of stem cells with their niche extracellular matrix is important for nearly all stem cell types of the body. The European Medicines Agency approved the first stem cell therapy in 2015 for the treatment of damaged cornea, and the applications of different stem cells in the repairing of tissues are under intensive investigation currently. According to Sipilä, one of the great challenges of stem cell research is to create an artificial laboratory environment, in which the cells can adhere supporting cell renewal and differentiation as in a normal tissue.
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Antibiotic resistance is a ticking bomb under public health. WHO predicts that in 2050 more people will die from infections than from cancer — and we are talking about infections that we today consider harmless; infections that occur in a cut or wound — or perhaps cystitis.
The reason is that bacteria are masters at adapting. When their existence is threatened, they mutate into a new and improved version of themselves that can no longer be threatened by eg antibiotics. Consequently, many disease-causing bacteria today are resistant to antibiotics.
“That’s bacteria for you. They always find a way! Of course, resistance will occur; that’s how evolution works,” says professor and head of research, Birgitte Kallipolitis, who studies disease-causing bacteria at the Department of Biochemistry and Molecular Biology at University of Southern Denmark.
The talents of fatty acids
And that’s exactly why, like other researchers around the world, she thinks it’s time to find new ways to fight or neutralize the perpetually mutating bacteria.
For some years now, she and her research group have studied a particular type of fatty acid, which has proven itself interesting in this context. The researchers use listeria as a bacterial model to test the effect of these fatty acids. Elsewhere in the world, colleagues are using salmonella and cholera bacteria for similar tests.

Many people have now embraced the plant-based meat movement. Plants high in protein, such as soybeans, are common ingredients, but it’s been unclear how much of the nutrient makes it into human cells. In ACS’ Journal of Agricultural and Food Chemistry, researchers report that proteins in a model plant-based substitute were not as accessible to cells as those from meat. The team says this knowledge could eventually be used to develop more healthful products.
Consumers can now buy almost any type of alternative meat, from ground beef to fish sticks. To mimic the look and texture of the real thing, plants are dehydrated into a powder and mixed with seasonings. Then, the mixtures are typically heated, moistened and processed through an extruder. These products are often thought of as being more healthful than animal meats because the plants used to make them are high in protein and low in undesirable fats. However, lab tests have shown that proteins in substitutes don’t break down into peptides as well as those from meats. Osvaldo Campanella, Da Chen and colleagues wanted to go a step further and see if human cells can absorb similar amounts of peptides from a model meat alternative as they can from a piece of chicken.
The researchers created a model meat alternative made of soy and wheat gluten with the extrusion process. When cut open, the material had long fibrous pieces inside, just like chicken. Cooked pieces of the substitute and chicken meat were then ground up and broken down with an enzyme that humans use to digest food. In vitro tests showed that meat-substitute peptides were less water-soluble than those from chicken, and they also were not absorbed as well by human cells. With this new understanding, the researchers say the next step is to identify other ingredients that could help boost the peptide uptake of plant-based meat substitutes.
The authors acknowledge funding from the College of Food, Agricultural, and Environmental Sciences at The Ohio State University.
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Amyotrophic lateral sclerosis (ALS) is a progressive disease of the nervous system. It affects nerve cells in the brain and spinal cord called motor neurons. Motor neurons control muscle movement and ALS causes them to deteriorate and eventually die. The motor neurons lose the ability to send messages to the muscles in the body, affecting voluntary muscle movements. There have been recent advances in treating ALS, but current treatments can only slow disease progression. That is why it is important to diagnose ALS as early as possible.
ALS is difficult to diagnose because, currently, there is no single test that can confirm the disease. Doctors look for neurological symptoms such as muscle weakness and upper and lower motor neuron symptoms. They will also do diagnostic tests to rule out other conditions like cervical spondylosis. A diagnostic test that could confirm ALS would help people get a diagnosis earlier and start treatment as soon as possible.
In a paper published on May 23 in JAMA Neurology, researchers outline preliminary research that could pave the way for a future test to diagnose ALS.
“It is difficult to diagnose ALS in its early stages because there is not a known biomarker,” said researcher Hirofumi Maruyama, a professor at the Graduate School of Biomedical and Health Sciences at Hiroshima University in Hiroshima, Japan. “Muscle is possible to biopsy, and transactive response DNA-binding protein 43 (TDP-43) accumulates in the peripheral nerves inside muscle. TDP-43 is a protein that plays a key role on motor neurons, and accumulation of TDP-43 may be a biomarker for early diagnosis of ALS.”
Previous research in mice has revealed a crucial function of TDP-43 in axons, the part of the neuron that sends signals to other neurons. This is important for ALS, because axonal degeneration causes the lower motor neuron problems that can be a symptom of ALS. Researchers hypothesized that TDP-43 accumulation in muscular nerve bundles could be an early predictor of ALS.
To test this theory, researchers first examined the muscle tissue of 10 individuals who had confirmed cases of ALS at the time of their death and 12 who did not. All 10 ALS patients had TDP-43 accumulations in their intramuscular nerve bundles, while 12 non-ALS controls had no TDP-43 accumulation.
Next, researchers targeted 114 patients who underwent a muscle biopsy and did not have a family history of ALS or another muscle or neuromuscular diagnosis. Of these, 71 had evidence of intramuscular nerve bundles and 43 did not. Among the 71 patients, axonal TDP-43 accumulations in their nerve bundles were confirmed in 33. These 33 patients with axonal TDP-43 accumulations were all later diagnosed with ALS. Among the 43 patients without nerve bundles, three were later diagnosed with ALS.
“Results of this dual case-control and cohort study suggest that axonal TDP-43 accumulations may be characteristic for patients with ALS, and consequently may be a novel diagnostic biomarker for ALS,” said Maruyama. “Early diagnosis enables patients to initiate prompt treatment. We aim to prevent the progression of ALS and will continue research into developing new medication.”
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Rensselaer Polytechnic Institute researchers have developed an accessible way to make N95 face masks not only effective barriers to germs, but on-contact germ killers. The antiviral, antibacterial masks can potentially be worn longer, causing less plastic waste as the masks do not need to be replaced as frequently.
Helen Zha, assistant professor of chemical and biological engineering and a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer (CBIS), collaborated with Edmund Palermo, associate professor of materials science and engineering and a member of the Center for Materials, Devices, and Integrated systems (cMDIS) at Rensselaer, to fight infectious respiratory disease and environmental pollution with the perfect recipe to improve face masks.
“This was a multifaceted materials engineering challenge with a great, diverse team of collaborators,” Palermo said. “We think the work is a first step toward longer-lasting, self-sterilizing personal protective equipment, such as the N95 respirator. It may help reduce transmission of airborne pathogens in general.”
In research recently published in Applied ACS Materials and Interfaces, the team successfully grafted broad-spectrum antimicrobial polymers onto the polypropylene filters used in N95 face masks.
“The active filtration layers in N95 masks are very sensitive to chemical modification,” said Zha. “It can make them perform worse in terms of filtration, so they essentially no longer perform like N95s. They’re made out of polypropylene, which is difficult to chemically modify. Another challenge is that you don’t want to disrupt the very fine network of fibers in these masks, which might make them more difficult to breathe through.”
Zha and Palermo, along with other researchers from Rensselaer, Michigan Technological Institute, and Massachusetts Institute of Technology, covalently attached antimicrobial quaternary ammonium polymers to the fiber surfaces of nonwoven polypropylene fabrics using ultraviolet (UV)-initiated grafting. The fabrics were donated by Hills Inc. courtesy of Rensselaer alumnus Tim Robson.

A new combination therapy to combat cancer could one day consist of a plant virus and an antibody that activates the immune system’s “natural killer” cells, shows a study by researchers at the University of California San Diego.
In mouse models of colon cancer, the combination therapy eliminated all tumors and prevented their recurrence, which in turn resulted in 100% survival. The therapy also increased survival in mouse models of melanoma.
The work is reported in a paper published June 17 in Nano Letters.
The proof-of-concept therapy enhances the activity of cancer killing immune cells known as natural killer cells, which naturally reside in the body and in tumors. The job of natural killer cells is to target and destroy cancer cells — in doing so, they release molecules called antigens that the immune system can recognize and produce antibodies against.
The problem is that there are not enough natural killer cells in or near cancerous tumors to be effective. And those that are in the tumors cannot do their job because cancer cells can secrete molecules that bind to natural killer cells and suppress them.
The therapy overcomes these problems using two key ingredients: cowpea mosaic virus, which is a plant virus that infects legumes but is harmless to animals and humans, and an antibody called anti-4-1BB. Cowpea mosaic virus has a special ability to attract natural killer cells to the tumor microenvironment, while anti-4-1BB binds to receptors on these cells to snap them out of their immunosuppressed state. By joining forces, the plant virus and antibody not only draw a large enough crowd of natural killer cells to the tumors, but also fire them up for attack.