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Indiana University School of Medicine researchers found that niacin limits Alzheimer’s disease progression when used in models in the lab, a discovery that could potentially pave the way toward therapeutic approaches to the disease.
The study, recently published in Science Translational Medicine, investigates how niacin modulates microglia response to amyloid plaques in an Alzheimer’s disease animal model.
Gary Landreth, PhD, Martin Professor of Alzheimer’s Research, and Miguel Moutinho, PhD, postdoctoral fellow in Anatomy, Cell Biology and Physiology, led the study.
“This study identifies a potential novel therapeutic target for Alzheimer’s disease, which can be modulated by FDA-approved drugs,” Moutinho said. “The translational potential of this strategy to clinical use is high.”
Niacin, which sustains metabolism throughout the body, is mainly obtained through a typical diet; it also can be taken in supplements and cholesterol-lowering drugs. The brain, however, Moutinho found, uses niacin in a different manner.
In the brain, niacin interacts with a highly-selective receptor, HCAR2, present in immune cells physically associated with amyloid plaques. When niacin — used in this project as the FDA-approved Niaspan drug — activates the receptor, it stimulates beneficial actions from these immune cells, Landreth said.
“After the Alzheimer’s disease animal models received niacin, they ended up with fewer plaques and they have improved cognition,” Landreth said, “and we directly showed that these actions were due to the HCAR2 receptor.”
Past epidemiology studies of niacin and Alzheimer’s disease showed that people who had higher levels of niacin in their diet had diminished risk of the disease, Landreth said. Niacin is also currently being used in clinical trials in Parkinson’s disease and glioblastoma.
To further their research into niacin and the brain, Landreth and Moutinho are collaborating with Jared Brosch, MD, associate professor of clinical neurology, who is applying for a clinical pilot trial to study the affects of niacin and the human brain.
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Materials provided by Indiana University School of Medicine. Note: Content may be edited for style and length.

In-vitro fertilization (IVF) clinics that offer money-back guarantees (MBGs) for their services achieve a higher live-birth success rate with less aggressive treatments than clinics that do not provide money-back guarantees.
In research recently published in the Journal of Marketing Research, Shan Yu, an assistant professor in the Lally School of Management at Rensselaer Polytechnic Institute, explored the question: Are MBG programs by IVF clinics marketing gimmicks that take advantage of consumers or a way for clinics to signal high-quality service?
Using a unique data set compiled from four distinct sources to undertake a systematic, clinic-level empirical analysis, Dr. Yu found that, on average, even when they transfer fewer embryos and do not sort patients according to their fertility, clinics using the marketing tool of MBGs achieve higher success rate and do not impose higher multiple birth risks. These results indicate that clinics that offer MBGs provide higher quality of service than clinics that do not offer MBGs.
According to Dr. Yu, consumers and policy-makers can use the presence of this marketing practice as a signal of high-quality care in the increasingly important field of IVF and other health-care and expert-service markets.
“In medicine, marketing practices are often perceived as a necessary evil,” Dr. Yu said. “Our study suggests that market-based promotional devices like money-back guarantees can serve as a necessary good for consumers.”
In a typical MBG plan, patients pay a set fee for a certain number of treatment cycles. If the patient does not deliver a live baby by the end of the treatment cycles, the patient receives a refund. If the patient delivers an infant at any point in the treatment plan, the clinic retains the payment in full.
With this type of expert-service market, the doctor holds far more knowledge than the patient, a factor known as information asymmetry. Because of this imbalance of knowledge, many critics argue that the pressure to return full payment motivates clinics to use MBG programs to entice less-informed patients and boost their success rate by using more aggressive treatment protocols or by sorting more fertile patients to their clinics. Both behaviors will decrease consumer welfare in the long term.
In the study, Dr. Yu accounted for these factors and found the critics’ fears to be unfounded. The data showed that clinics offering MBGs achieved enhanced quality of care by securing better outcomes despite taking lower risks and without sorting for the most fertile patients.
“This suggests that MBG programs may not necessarily be marketing ploys employed to entice less informed and more vulnerable patients,” Dr. Yu said. “Through experience, clinics may have developed a repository of skills and expertise that make them confident in offering MBG programs without undertaking adverse actions.”
The research further showed that clinics are more likely to offer MBGs in states without a mandate for insurance companies to cover IVF treatment costs, suggesting that MBGs also serve as a market-driven insurance device, in particular for lower-fertility patients.
“The results of this study are consistent with signaling theory predictions that money-back guarantees can serve as signals of unobservable clinic quality despite the incentives for clinics to engage in opportunistic behaviors,” Dr. Yu said. “These findings offer policy guidance and improve patient welfare in a complex expert-service market fraught with information asymmetry.”
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Materials provided by Rensselaer Polytechnic Institute. Original written by Jeanne Hedden Gallagher. Note: Content may be edited for style and length.

Scientists have discovered a new family of helpful proteins in the lung, with the finding potentially paving the way for a new course of treatment for patients with respiratory failure.
Researchers from Anglia Ruskin University (ARU), alongside colleagues from Brown University and the Providence Veterans Affairs Medical Center in Rhode Island, US, have identified for the first time that bitter taste receptors commonly found in the tongue, called T2Rs, are also present in the walls of blood vessels in the lung.
Over 10% of patients in intensive care units worldwide suffer from acute respiratory distress syndrome (ARDS), and it has a mortality rate of nearly 40%. ARDS requires patients to undergo ventilation and is commonly caused by pneumonia, major surgery, trauma, sepsis, and, more recently, COVID-19.
ARDS is associated with an excessive increase in pulmonary vascular permeability, which allows proteins and liquids to enter the lung leading to the development of pulmonary edema, commonly referred to as ‘water on the lungs’.
The new study, led by Dr Zsuzsanna Kertesz and Dr Havovi Chichger of Anglia Ruskin University (ARU) in Cambridge, England, and published in the journal Frontiers in Physiology, has discovered that when these bitter taste receptors in the lung are stimulated, they help to protect the lining of the blood vessels, called the endothelium.
The researchers found that the compounds phenylthiocarbamide and denatonium — the most bitter substance known — act on bitter taste receptors T2R38 and T2R10, respectively. Once stimulated, the bitter taste receptors provide a protective mechanism for the wall of the blood vessels, preventing barrier disruption and stopping liquids from passing through.
Senior author Dr Havovi Chichger, Associate Professor in Biomedical Science at Anglia Ruskin University (ARU), said: “One of the biggest issues that Intensive Care Unit patients with COVID, trauma or bacterial infection suffer from is respiratory distress, commonly diagnosed as acute respiratory distress syndrome. This is an inability to get enough oxygen into the body because of fluid leak from blood vessels into the lung.
“In this new study, we have identified a new family of proteins in blood vessels in the lung called T2R, or bitter taste receptors. These are the same proteins found in the tongue which sense any bitter substances and tell us that they taste unpleasant. In blood vessels in the lung, we show that these bitter taste receptors are able to regulate how our blood vessels function when stressed.
“Most intriguingly, when we stimulate these proteins, we have found that they offer protection against fluid leak. These findings indicate that this new family of proteins in blood vessels could offer a new avenue of drugs to reduce fluid leak into the lung, and therefore help to treat patients with respiratory distress.”
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Materials provided by Anglia Ruskin University. Note: Content may be edited for style and length.

Pancreatic cancer is notoriously difficult to cure or even treat. Now, a new strategy devised by scientists at Albert Einstein College of Medicine has succeeded in making pancreatic tumors visible to the immune systems of mice and vulnerable to immune attack, reducing cancer metastases by 87%. The paper describing the findings published online today in Science Translational Medicine.
“Today’s checkpoint inhibitor drugs work well against some types of cancer but only rarely help people with pancreatic cancer,” said Claudia Gravekamp, Ph.D., corresponding author of the paper and associate professor of microbiology & immunology at Einstein and a member of the National Cancer Institute-designated Albert Einstein Cancer Center. “The problem is that pancreatic tumors aren’t sufficiently ‘foreign’ to attract the immune system’s attention and can usually suppress whatever immune responses do occur. Essentially, our new therapy makes immunologically ‘cold’ tumors hot enough for the immune system to attack and destroy them.”
Leveraging the Tetanus Vaccine
Dr. Gravekamp’s treatment strategy capitalizes on the fact that virtually all people are vaccinated in childhood against tetanus, a serious disease caused by a toxic protein that Clostridium bacteria secrete. Thanks to their tetanus-specific memory T cells, which circulate in the bloodstream for life, vaccinated people will mount a strong immune response if they’re later exposed to the highly foreign tetanus toxin. Dr. Gravekamp and her colleagues effectively aroused a potent and specific immune response against pancreatic cancer cells by infecting them with bacteria that deliver tetanus toxin into the cells.
Using the same tetanus vaccine given to people, the investigators vaccinated mouse models of pancreatic cancer (i.e., mice bearing human pancreatic tumors). They then fused the gene that codes for tetanus toxin into non-disease-causing Listeria monocytogenes bacteria, which are highly adept at infecting cells and spreading through tissues. Finally, to infect and “tetanize” the tumors, they injected the bacteria with their tetanus-gene cargoes into the previously vaccinated, tumor-bearing mice.
Exploiting Cancer’s Immune Suppression
“The Listeria bacteria are quite weak and are readily killed off by the immune systems of people and animals — everywhere, that is, except in tumor areas,” said Dr. Gravekamp. “Our treatment strategy actually takes advantage of the fact that pancreatic tumors are so good at suppressing the immune system to protect themselves. This means that only those Listeria bacteria in the tumor region survive long enough to infect pancreatic tumor cells and that healthy cells don’t become infected.”
Once the Listeria bacteria infected the tumor cells, their tetanus-toxin genes expressed the tetanus-toxin protein inside the tumor cells — triggering a strong immune response. The tetanus toxin activated pre-existing tetanus-specific memory T cells, causing CD4 T cells to attack and kill the infected tumor cells. The T cell responses were enhanced by adding low doses of gemcitabine (a chemotherapy drug that reduces immune suppression). The treatment shrank the size of the pancreatic tumors in the mice by an average of 80% and also significantly reduced the number of metastases by 87%, while the treated animals lived 40% longer than untreated (control) animals.
“The findings indicate that this treatment approach could be a useful immunotherapy for pancreatic cancer as well as other types of cancer, such as ovarian cancer, that remain difficult to treat,” said Dr. Gravekamp.
Dr. Gravekamp is an associate professor of microbiology & immunology at Einstein. Einstein has licensed the underlying technology to Loki Therapeutics., which plans to commercialize the technology further to benefit patients. Dr. Gravekamp is the co-founder of Loki Therapeutics and its principal scientist.
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Materials provided by Albert Einstein College of Medicine. Note: Content may be edited for style and length.

Tiny biological computers made of DNA could revolutionize the way we diagnose and treat a slew of diseases, once the technology is fully fleshed out. However, a major stumbling block for these DNA-based devices, which can operate in both cells and liquid solutions, has been how short-lived they are. Just one use and the computers are spent.
Now, researchers at the National Institute of Standards and Technology (NIST) may have developed long-lived biological computers that could potentially persist inside cells. In a paper published in the journal Science Advances, the authors forgo the traditional DNA-based approach, opting instead to use the nucleic acid RNA to build computers. The results demonstrate that the RNA circuits are as dependable and versatile as their DNA-based counterparts. What’s more, living cells may be able to create these RNA circuits continuously, something that is not readily possible with DNA circuits, further positioning RNA as a promising candidate for powerful, long-lasting biological computers.
Much like the computer or smart device you are likely reading this on, biological computers can be programmed to carry out different kinds of tasks.
“The difference is, instead of coding with ones and zeroes, you write strings of A, T, C and G, which are the four chemical bases that make up DNA,” said Samuel Schaffter, NIST postdoctoral researcher and lead author of the study.
By assembling a specific sequence of bases into a strand of nucleic acid, researchers can dictate what it binds to. A strand could be engineered to attach to specific bits of DNA, RNA or some proteins associated with a disease, then trigger chemical reactions with other strands in the same circuit to process chemical information and eventually produce some sort of useful output.
That output might be a detectable signal that could aid medical diagnostics, or it could be a therapeutic drug to treat a disease.

Scientists already know that the venom of cone snails, which prowl the ocean floor for a fish dinner, contains compounds that can be adapted as pharmaceuticals to treat chronic pain, diabetes and other human maladies. But the cone snails’ venom has more secrets yet to be revealed. In a new study published in Science Advances, researchers report that a group of cone snails produces a venom compound similar to the hormone somatostatin.
While they continue to learn more about this venom compound and its possible pharmaceutical applications, the results show the wide variety of drug leads that venomous animals produce, designed and refined over millions of years.
“We have to broaden the scope of what we expect that these venomous animals make, assuming that they could really be making anything,” says Helena Safavi-Hemami, an adjunct assistant professor at the University of Utah and associate professor at the University of Copenhagen. “We should look very broadly and keep an open eye for completely new compounds.”
“Cone snail venom is like a natural library of compounds,” adds Iris Bea Ramiro of the University of Copenhagen. “It is just a matter of finding what is in that library.”
Find the full study here. This research was funded by the U.S. Department of Defense, a Villum Young Investigator Grant, the Department of Science and Technology — Philippine Council for Health Research and Development, USAID and the Benning Society.
Beginning in Bohol
The story begins in the Philippines, on the island of Bohol where Ramiro grew up. Although she and most Boholanos didn’t encounter cone snails often except for finding shells on the beach, fishermen knew how to find and catch the venomous snails, which are often sold to shell collectors and are sometimes eaten. One fisherman told Ramiro that his parents warned him to avoid eating a bean-like organ in the snail.

A University of Iowa neuroscience research team has identified a fundamental biochemical mechanism underlying memory storage and has linked this mechanism to cognitive deficits in mouse models of Alzheimer’s Disease and Related Dementias.
While working to understand how memories are formed and stored in the brain, the team identified a novel protein folding mechanism in the endoplasmic reticulum that is essential for long term memory storage. They further demonstrated that this mechanism is impaired in a tau-based mouse model of Alzheimer’s disease and that restoring this protein folding mechanism reverses memory impairment in this mouse model for the study of dementia. The findings are published in the March 23 issue of the journal Science Advances.
The team was led by Snehajyoti Chatterjee, PhD, a research associate in the lab of Ted Abel, PhD, Director of the Iowa Neuroscience Institute and chair and DEO of the UI Department of Neuroscience and Pharmacology. The Abel lab has previously shown that the Nr4a family of transcription factors is essential for long term memory consolidation. This study identified chaperone proteins in the endoplasmic reticulum, which are regulated by Nr4a.
“The role of protein folding machinery in long term memory has been overlooked for decades,” Chatterjee says. “We know that gene expression and protein synthesis are essential for long term memory consolidation and following learning a large number of proteins are synthesized. For proteins to be functionally active they need to be folded correctly. Our work demonstrates the conceptual idea that these chaperone proteins are the ones that actually fold the proteins to impact synaptic function and plasticity.”
The team also used gene therapy to reactivate the chaperone protein in a mouse model and found that the memory deficit was reversed, confirming that the protein folding machinery acts as a molecular switch for memory.
“Identifying this protein folding mechanism is a crucial step toward understanding how memories are stored and what goes wrong in diseases associated with memory impairment,” Abel says. “Even though we are not yet at a point of translating this to patient care, understanding this pathway is essential to one day being able to prevent and treat neurodegenerative disease.”
In addition to Chatterjee and Abel, the research team included Jacob Michaelson, UI associate professor of psychiatry; postdoctoral scholar Mahesh Shivarama Shetty; graduate students Ethan Bahl, Utsav Mukherjee, Yann Vanrobaeys, and Emily N. Walsh; lab assistants Amy L. Yan and Joseph D. Lederman; and K. Peter Giese of Kings College, London.
The work was supported by NIH grant R01 MH087463, NIH grant K99 AG 068306, Nellie Ball Trust, The Gary & LaDonna Wicklund Research Fund for Cognitive Memory Disorders, The University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center, and the Roy J. Carver Charitable Trust.
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Materials provided by University of Iowa Health Care. Original written by Mary Kenyon. Note: Content may be edited for style and length.

As soon as Edward Holmes saw the dark-ringed eyes of the raccoon dogs staring at him through the bars of the iron cage, he knew he had to capture the moment.It was October 2014. Dr. Holmes, a biologist at the University of Sydney, had come to China to survey hundreds of species of animals, looking for new types of viruses.On a visit to Wuhan, a commercial center of 11 million people, scientists from the city’s Center for Disease Control and Prevention brought him to Huanan Seafood Wholesale Market. In stall after stall of the poorly ventilated space, he saw live wild animals — snakes, badgers, muskrats, birds — being sold for food. But it was the raccoon dogs that made him pull out his iPhone.As one of the world’s experts on virus evolution, Dr. Holmes had an intimate understanding of how viruses can jump from one species to another — sometimes with deadly consequences. The SARS outbreak of 2002 was caused by a bat coronavirus in China that infected some kind of wild mammal before infecting humans. Among the top suspects for that intermediate animal: the fluffy raccoon dog.“You could not get a better textbook example of disease emergence waiting to happen,” Dr. Holmes, 57, said in an interview.The photos faded from his mind until the last day of 2019. As Dr. Holmes was browsing Twitter from his Sydney home, he learned of an alarming outbreak in Wuhan — a SARS-like pneumonia with early cases linked to the Huanan market. The raccoon dogs, he thought.“It was a pandemic waiting to happen, and then it bloody well happened,” he said.

Researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan have identified a gene necessary for the survival of retinal ganglion cells — a class of neurons located in the retina that are critical for vision.
Reporting in elife on March 22, 2022, the scientists found that when zebrafish embryos developed without a working version of a gene called strip1, most retinal ganglion cells died, and inner retinal layers formed abnormally. As well as providing fundamental insights into how the retina develops, discovering how the protein encoded by the strip1 gene keeps retinal ganglion cells alive also opens promising new avenues into treating diseases like glaucoma.
“Glaucoma is one of the leading causes of blindness worldwide, with the loss of vision caused by the death of retinal ganglion cells,” said Professor Ichiro Masai, head of the Developmental Neurobiology Unit at OIST. “In the future, uncovering the full Strip1 protein pathway inside retinal ganglion cells could help scientists find ways to slow down, or even prevent, their death in patients with glaucoma.”
Prof. Masai, along with his PhD student, Mai Ahmed, first became interested in the strip1 gene due to its role in correctly forming inner retinal layers.
“When you look at the retina under a microscope, you can see that it has this beautifully organized structure. Different neurons are stacked on top of each other, with synaptic layers in between where the neurons connect and communicate to each other,” said first author, Mai Ahmed. “These neurons carry electrical signals from the photoreceptors that detect light all the way to the visual centers of the brain. Without proper wiring of these retinal circuits, vision is compromised.”
Back in the early 2000s, scientists at RIKEN in Japan, including Prof. Masai, created hundreds of zebrafish embryos that contained random mutations. They saw that one of these mutations caused a defect in a synaptic layer in the retina, known as the inner plexiform layer. Further research at OIST identified that the mutation occurred within the gene, strip1.
Seeking to uncover the reason behind this retinal defect, Prof Masai’s unit labelled the three different types of neurons that connect in the inner plexiform layer — retinal ganglion cells, amacrine cells and bipolar cells — to see how they developed when strip1 was mutated.
Surprisingly, the researchers found that while all three neuron types developed an incorrect form and position, only the retinal ganglion cells died. As these cells died, the other neuron types replaced them, leading to a disordered layer. The Strip1 protein is therefore essential for keeping ganglion cells alive, and thus maintaining the correct form of the inner plexiform layer.
When the researchers looked at the underlying mechanism, they found that Strip1 suppresses the activity of Jun, a protein associated with cell death. Jun, and the pathway it acts within, is triggered when neurons are under stress. If enough of the Jun protein is activated, the cell dies.
“This process of cell death, called apoptosis, is a fail-safe mechanism for removing stressed cells that can’t be repaired,” explained Prof. Masai. “But we believe retinal ganglion cells are placed under immense metabolic stress during normal development, when they form the incredibly long optic nerve. So Strip1 is needed inside retinal ganglion cells to protect them from the Jun apoptotic pathway.”
Importantly, Jun, and the pathway it acts within, is known to play a role in the death of retinal ganglion cells in patients with glaucoma.
“Glaucoma typically occurs when pressure damages the optic nerve, placing the retinal ganglion cells under immense stress, and activating Jun,” said Mai. “If, in future research, it’s found that Strip1 can suppress Jun in mammalian glaucoma models too, this would open the door to many new therapies.”

How the ‘second brain’ — the enteric nervous system in our gut — communicates with our first brain has been one of the most challenging questions faced by enteric neuroscientists, until now.
New research from Flinders University has discovered how specialised cells within the gut can communicate with both the brain and spinal cord, which up until now had remained a major mystery.
“The gut-brain axis consists of bidirectional communication between the brain and the gut, which links emotional and cognitive centres of the brain with peripheral intestinal functions,” says study author Professor Nick Spencer from the College of Medicine and Public Health.
“Recent advances in research have described the importance of gut microbiota in influencing these pathways but we had yet to uncover how the communication was working.”
The study, published in the American Journal of Physiology, reveals a breakthrough discovery regarding how enterochromaffin cells communicate with sensory nerve endings.
“Within the gut wall lie specialised cells called enterochromaffin (EC) cells that produce and release hormones and neurotransmitters in response to particular stimuli that are ingested when we eat,” says Professor Spencer.