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Scientists have identified a chemical pathway to an innovative insulating nanomaterial that could lead to large-scale industrial production for a variety of uses — including in spacesuits and military vehicles. The nanomaterial — thousands of times thinner than a human hair, stronger than steel and noncombustible — could block radiation to astronauts and help shore up military vehicle armor, for example.
Collaborative researchers at the U.S. Department of Energy’s (DOE) Princeton Plasma Physics Laboratory (PPPL) have proposed a step-by-step chemical pathway to the precursors of this nanomaterial, known as boron nitride nanotubes (BNNT), which could lead to their large-scale production.
“Pioneering work”
The breakthrough brings together plasma physics and quantum chemistry and is part of the expansion of research at PPPL. “This is pioneering work that takes the Laboratory in new directions,” said PPPL physicist Igor Kaganovich, principal investigator of the BNNT project and co-author of the paper that details the results in the journal Nanotechnology.
Collaborators identified the key chemical pathway steps as the formation of molecular nitrogen and small clusters of boron, which can chemically react together as the temperature created by a plasma jet cools, said lead author Yuri Barsukov of the Peter the Great St. Petersburg Polytechnic University. He developed the chemical reaction pathways by performing quantum chemistry simulations with the assistance of Omesh Dwivedi, a PPPL intern from Drexel University, and Sierra Jubin, a graduate student in the Princeton Program in Plasma Physics.
The interdisciplinary team included Alexander Khrabry, a former PPPL researcher now at Lawrence Livermore National Laboratory who developed a thermodynamic code used in this research, and PPPL physicist Stephane Ethier who helped the students compile the software and set up the simulations.

A new Cornell study has found the antimicrobial properties of certain stem cell proteins could offer a potential treatment to reduce infection in skin wounds.
Treating wounds with the secretion of a type of stem cell effectively reduced the viability of methicillin-resistant Staphylococcus aureus — better known as MRSA — according to a new study from researchers at the Baker Institute for Animal Health, part of the College of Veterinary Medicine (CVM). Moreover, the secretion stimulated the surrounding skin cells to build up a defense against the bacterial invader, the researchers found.
The study appeared Sept. 16 in Stem Cells Translational Medicine.
“The results showed that secreted factors from equine mesenchymal stromal cells (MSCs), a type of stem cell, significantly decreased the viability of MRSA in our novel skin model,” said first author Dr. Charlotte Marx, a postdoctoral researcher in the lab of corresponding author Dr. Gerlinde R. Van de Walle, associate professor of microbiology and immunology at CVM.
“Moreover,” Marx said, “we demonstrated that equine MSC secretions increase the antimicrobial activity of the skin cells by stimulating immune responses of the surrounding resident skin cells.”
In 2017, more than 119,000 people in the U.S. suffered from bloodstream infections caused by MRSA — and nearly 20,000 died, according to the most recent statistics from the Centers for Disease Control and Prevention. MRSA has become a major health care problem because these bacteria can become threatening under certain circumstances, such as in immunocompromised patients or in infected wounds, and because they have grown resistant to many antibiotics — the only medications currently available to treat bacterial infections.

New discoveries about a built-in rapid reaction system that triggers inflammatory responses when people are exposed to allergens, such as insects, mites and fungi, also may hold the keys to helping more people manage their allergies in years to come.
A study led by scientists at Cincinnati Children’s, published Sept. 16, 2021, in Nature Immunology reveals new details about how the body’s “type 2 innate immune response” system works. By identifying a common biological response platform, the findings suggest that any new medication that can control the response could benefit people suffering from a wide range of allergies.
“Disrupting this allergen sensing pathway could provide a unique opportunity to counteract type 2 immunity and alleviate allergic inflammation,” says Marc Rothenberg, MD, PhD, Director of the Division of Allergy and Immunology at Cincinnati Children’s and senior author on the study.
In addition to Rothenberg, the research team included Michael Brusilovsky, MMedSc, PhD, Mark Rochman, PhD, Yrina Rochman, PhD, Julie Caldwell, PhD. Lydia Mack, MS, Jennifer Felton, PhD, Jeff Habel, PhD, Aleksey Porollo, PhD and Chandrashekhar Pasare, DVM, PhD.
Previous research had established that multiple allergens can induce a similar IL-33 response upon breaching the epithelial layer of mucosal membranes. The Cincinnati Children’s team pinned down the mechanisms at work in the process.
Allergen sensing system
“This breakthrough was made possible by new insights into role of ripoptosome signaling and caspases in allergic inflammation,” says Brusilovsky, who was first author on the study.

Dr. Christina Strauch, PhD student Thu-Huong Hoang, and Professor Denise Manahan-Vaughan from the Department of Neurophysiology collaborated on the study with Professor Frank Angenstein from the German Center for Neurodegenerative Diseases (DZNE) in Magdeburg.
Olfactory perception outside the olfactory bulb and the olfactory cortex
The researchers studied how the processing of scents affects structures in the brain. They used electrical impulses to stimulate the olfactory bulbs of test animals. Then, they analysed the activity in the olfactory cortex, where olfactory stimuli are processed. “We already knew that there is a connection between the olfactory bulb and the piriform cortex, a part of the olfactory cortex, in the perception of scents,” explains Dr. Christina Strauch, lead author of the study. “But our goal was to go deeper into the brain structures and find out which regions we had underestimated or overlooked until now.” “So far, only a few studies on olfactory perception have analysed regions outside the olfactory bulb and olfactory cortex regions in rodents,” says Professor Denise Manahan-Vaughan, spokesperson of Collaborative Research Centre 874 Integration and Representation of Sensory Processes. “It is still not completely understood how olfactory memories are formed. Our goal was to clarify to what extent brain structures that aren’t part of the olfactory system are involved in olfactory memory formation.”
Evidence of olfactory processing in the rodent brain
In their study, the researchers combined electrophysiological stimulation with functional magnetic resonance imaging (fMRI). Following this approach, the team obtained a detailed picture of the neuronal structures that responded to the stimulation of the olfactory bulb. Highly responsive structures were then analysed in more depth using fluorescence in situ hybridisation analysis of neuronal gene expression. This technique helps researchers determine whether neurons do indeed store the olfactory stimulus: This event serves as evidence of memory formation.
Sure enough, stimulation of the olfactory bulb had led to altered gene activity. This happened even in the nerve cells of the limbic cortex — that is, in a functional unit attributed with the processing of emotions. “The involvement of these non-olfactory structures probably plays a key role in the storage of olfactory experiences,” as Christina Strauch interprets the findings. “We deduce from this that rodents quickly categorise perceived scents as pleasant or unpleasant while smelling them.”
Overall, the results prove that the olfactory system works closely with the brain’s reward and aversion systems in both learning and memory formation.
“The study provides us an additional theoretical basis for understanding why the sense of smell plays such a unique role in the formation and retrieval of memories,” says Denise Manahan-Vaughan, who together with Christina Strauch has been exploring how memories are formed from scents since 2010.
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Bristol-led research has identified specific drug targets within the neural circuits that encode memories, paving the way for significant advances in the treatment of a broad spectrum of brain disorders.
Loss of memory is a core feature of many neurological and psychiatric disorders including Alzheimer’s disease and schizophrenia. Current treatment options for memory loss are very limited and the search for safe and effective drug therapies has, until now, had limited success.
The research was done in collaboration with colleagues at the international biopharmaceutical company Sosei Heptares. The findings, published in Nature Communications, identify specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits in the hippocampus. Acetylcholine is released in the brain during learning and is critical for the acquisition of new memories. Until now, the only effective treatment for the symptoms of cognitive or memory impairment seen in diseases such as Alzheimer’s is using drugs that broadly boost acetylcholine. However, this leads to multiple adverse side effects. The discovery of specific receptor targets that have the potential to provide the positive effects whilst avoiding the negative ones is promising.
Lead author, Professor Jack Mellor, from the University of Bristol’s Centre for Synaptic Plasticity, said: “These findings are about the fundamental processes that occur in the brain during the encoding of memory and how they may be regulated by brain state or drugs targeting specific receptor proteins. In the long-term, the discovery of these specific targets opens up avenues and opportunities for the development of new treatments for the symptoms of Alzheimer’s disease and other conditions with prominent cognitive impairments. The academic-industry partnership is important for these discoveries and we hope to continue working together on these projects.”
Dr Miles Congreve, Chief Scientific Officer at Sosei Heptares, added: “These important studies have helped us to design and select new, exquisitely targeted therapeutic agents that mimic the effects of acetylcholine at specific muscarinic receptors, without triggering the unwanted side effects of earlier and less-well targeted treatments. This approach has the exciting potential to improve memory and cognitive function in patients with Alzheimer’s and other neurological diseases.”
“It is fascinating how the brain prioritises different bits of information, working out what is important to encode in memory and what can be discarded. We know there must be mechanisms to pull out the things that are important to us but we know very little about how these processes work. Our future programme of work aims to reveal how the brain does this using acetylcholine in tandem with other neurotransmitters such as dopamine, serotonin and noradrenaline,” said Professor Mellor.
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Most non-mammalian vertebrates have a color detection system in the pineal organ of the brain that is located in a single cell. In collaboration with Nara Women’s University, a new study from the Department of Biology and Geosciences, Osaka City University Graduate School of Science has discovered a two-cell system in the lamprey, a jawless fish that retains many primitive features among vertebrates. The research group proposed that single-cell color detection in most fish and reptiles evolved from a two-cell system.
The research group has previously shown that, unlike the lamprey, the pineal organ of fish and reptiles detects color through two types of light-sensitive proteins called opsins located in a single cell. This new study led by Professor Akihisa Terakita, found that the UV-sensitive parapinopsin and green-sensitive parietopsin that are present in a single photoreceptor cell of fish and reptiles, are expressed in separate cells of the lamprey.
Their findings were published in BMC Biology.
“In addition to eyes, fish and reptiles use a “third eye” called the pineal organ, or the pineal gland, to detect color,” states Professor Mitsumasa Koyanagi. “Based on these new results, we propose a surprising scenario where the color detection mechanism of the pineal organ, which was divided into two cells, was integrated into a single cell during evolution.”
In the study, the team analyzed the pineal color detection system of the lamprey and compared it with the single-cell systems found in fish and reptiles. Through DNA sequencing, they identified a set of genes in the lamprey that encode two opsins found in the single-cell system. To their surprise, analysis of the protein gene expression found that these opsins were expressed in separate cells. “This suggests that the pineal organ of the lamprey is not a one-cell system, but a system in which two types of opsins are present in different photoreceptor cells,” states Dr. Seiji Wada.
From previous studies, the research team knew that the single-cell system produces a response of hyperpolarization when UV light is received and depolarization in response to visible light. Electrophysiological analysis of cellular responses showed that the lamprey two-cell system was also sensitive to UV and visible light in the same way.
“To further solidify our hypothesis that the two-cell system similar to what we found in the more primitive lamprey, could be the evolutionary ancestor of the single-cell system of fish and reptiles,” states Professor Akihisa Terakita, “we also needed to investigate the proteins involved in converting light information into cellular responses.”
Called Gt and Go, the team found through immunohistochemical analysis that these proteins, which they had confirmed in previous research on zebrafish are used by UV- and visible-light responsive cell in the single-cell system, are responsible for the same responses in the two-cell system.
In previous work, the team checked the photoreceptor responses for the single cell system under various intensities of artificial light to show it works well even in strong light conditions. To clarify a potential benefit for this evolutionary change, the team investigated neurotransmitters in the two cells, and found that the UV and visible light-sensitive cells use the same neurotransmitter to integrate each signal to the next cell for generating color information. “We believe that the integration process at the neurotransmitter level could deteriorate the signal-to-noise ratio under strong light conditions,” states Seiji Wada.
Of the many possibilities this discovery unfolds, the teams focused on its implications with the human eye. The eye, which is responsible for vision, and the pineal organ, which is responsible for functions other than vision, have the same origin. The idea that the pineal organ’s color detection system evolved from a multi-cellular to single-cell system, while the eye is thought to have evolved complex neural circuits to handle multiple cells, should facilitate our understanding of visual and non-visual functions. This evolutionary insight suggests that to address issues with color blindness, rather than being limited to reconstructing a complex multicellular system, combining it into a single-cell system may become an option in the future.
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How should diagnostic tests developed in laboratories in hospitals and other health care settings be regulated — if at all? That’s a question that has stirred lively debate within the U.S. health care system for years, but certain temporary deviations in Food and Drug Administration (FDA) policy in response to the COVID-19 pandemic may offer a blueprint for regulatory oversight of laboratory-developed tests (LDTs), according to a new study by researchers at Massachusetts General Hospital (MGH) published in the Journal of Molecular Diagnostics. This research provides concrete data that suggests what FDA regulation of LDTs might look like. This data could help inform pending legislation aiming to change the regulatory oversight of certain “high risk” LDTs.
Diagnosing many human diseases relies on in vitro diagnostic (IVD) tests, which include tests performed in a test tube, culture dish, or elsewhere outside a living organism. (IVDs are also sometimes called in vitro clinical tests, or IVCTs.) The FDA already closely regulates commercially available IVDs, requiring manufacturers to submit data for premarket approval before they can be sold. However, clinical laboratories located in hospitals and other health care settings can create their own IVDs for in-house use, which are known as LDTs. Historically, the FDA has exercised little oversight of LDTs (so-called enforcement discretion).
However, that policy changed with the onset of the COVID-19 pandemic, notes Jochen Lennerz, MD, PhD, medical director of the MGH Center for Integrated Diagnostics (CID) and the study’s senior author. In March 2020, the FDA asserted authority over LDTs, requiring labs that produced them for detecting COVID-19 to undergo emergency use authorization (EUA). Requiring makers of LDTs to submit validation data to enable assessment of performance and accuracy of their assays was the first time the FDA took concrete steps to regulate in-house diagnostic tests, a significant deviation from policy.
That requirement was later rescinded and labs were once again allowed to administer LDTs without FDA authorization. However, the FDA required the makers of LDTs that had received EUAs and makers of manufactured tests to validate their products’ accuracy by running them on a reference panel that served as a gold standard for detecting COVID-19. This so-called labeling update study was a second deviation from FDA policy regarding regulation of LDTs.
Using data from their own lab, as well as from facilities around the nation, Lennerz and his colleagues analyzed the impact of these two deviations and found several key takeaways: Despite concerns that the FDA wasn’t responding fast enough, a timeline of the initial 14 tests to receive EUAs showed that the process took 17 days, on average, from submission to authorization. Validating an IVD’s accuracy with the FDA’s reference panel carries costs. A typical lab required about 14 hours of technician time to complete the process. Add materials and other expenses to labor costs and each lab spent between $1,800 and $7,800 in the labeling update study. IVDs for COVID-19 weren’t as sensitive as their makers initially reported. The labeling update study — which used a common reference standard known as limit of detection (LOD) — found the true LODs to be significantly higher for most of the tests, from both labs and manufacturers.Yet there’s critical data that the labeling update study did not measure, notes Lennerz. Manufacturers submitted data about the performance of their IVDs based on their own in-house testing. But how well do manufacturers’ IVDs perform in the real world, when they’re used in hospital pathology labs? “The quality of a diagnostic test relies heavily on the competence of people,” says Lennerz. “We all make errors from time to time. What the performance of manufacturers’ tests looks like routinely and across clinical laboratories remains a question mark. And we currently do not have the tools to assess this systematically.”
However, one of two bills that Congress is considering, the Verifying Accurate Leading-edge IVCT Development (VALID) Act, proposes mechanisms to expand regulatory oversight by the FDA. In one of these proposed mechanisms, known as technology certification, a laboratory would submit data about the design and performance of the highest-complexity test that it performs to the FDA, which would conduct a detailed review. This test would serve as a representative for the lab’s entire design-validation process. In contrast, the competing bill (known as the VITAL Act) does not provide such mechanisms or details. VALID proposes to place responsibility for oversight of high-risk LDTs in the hands of the FDA, which Lennerz feels is the right choice. “I think the FDA has the appropriate standing to obtain comprehensive comparison data and help establish tools to regulate complex diagnostic tests,” he says.
Lennerz is also an associate professor of Pathology at Harvard Medical School.
This work was funded in part by a grant from the National Institutes of Health.
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Women with higher levels of PFAS in their system may be 20% more likely to stop breastfeeding early, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Per- and polyfluoroalkyl substances (PFAS) are humanmade chemicals used as oil and water repellents and coatings for common products including cookware, carpets and textiles. These endocrine-disrupting chemicals do not break down when they are released into the environment, and they continue to accumulate over time. PFAS chemicals can affect pregnancy outcomes, the timing of puberty and other aspects of reproductive health.
“Our findings are important because almost every human on the planet is exposed to PFAS. These human-made chemicals accumulate in our bodies and have detrimental effects on reproductive health,” said the study’s first author Clara Amalie Gade Timmermann, Ph.D., assistant professor of the University of Southern Denmark in Copenhagen, Denmark. “Early unwanted weaning has been traditionally attributed to psychological factors, which are without a doubt important, but hopefully our research will help shift the focus and highlight that not all mothers can breastfeed despite good intentions and support from family and healthcare professionals.”
The researchers analyzed blood samples for PFAS and prolactin concentrations from up to 1,286 pregnant women from the Odense Child Cohort. The women provided information about the duration of breastfeeding in weekly text messages or questionnaires at three and eighteen months postpartum. The researchers found women with higher levels of PFAS in their system were 20% more likely to stop breastfeeding early.
“Because breastfeeding is crucial to promote both child and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences,” Timmermann said.
Other authors of the study include: Marianne Skovsager Andersen and Henriette Boye of the Odense University Hospital in Denmark; Esben Budtz-Jørgensen of the University of Copenhagen; Flemming Nielsen of the University of Southern Denmark; Richard Christian Jensen, Steffen Husby and Tina Kold Jensen of the University of Southern Denmark and the Odense University Hospital; Signe Bruun of the Odense University Hospital, the University of Southern Denmark and Arla Foods Ingredients Group; and Philippe Grandjean of the University of Southern Denmark and the Harvard T.H. Chan School of Public Health in Boston, Mass.
The study received funding from the Independent Research Fund Denmark, the Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, the Odense Patient data Explorative Network, Novo Nordisk and the National Institute of Environmental Health Sciences.
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Researchers at Université de Montréal and McGill University have discovered a new multi-enzyme complex that reprograms metabolism and overcomes “cellular senescence,” when aging cells stop dividing.
In their study published today in Molecular Cell, the researchers show that an enzyme complex named HTC (hydride transfer complex) can inhibit cells from aging.
“HTC protects cells from hypoxia, a lack of oxygen that normally leads to their death,” said senior author Gerardo Ferbeyre, an UdeM biochemistry professor and principal scientist at the CRCHUM, the university’s affiliated teaching hospital research centre.
“Importantly, HTC can be hijacked by certain cancer cells to improve their metabolism, resist to a hypoxic environment and proliferate,” said Ferbeyre, who made the discovery with Sebastian Igelmann, a PhD student in his lab and first author of the study.
HTC is made up of three enzymes: pyruvate carboxylase, malate dehydrogenase?1 and malic enzyme?1. They were all highly expressed in samples from a prostate cancer mouse model generated at the University of Veterinary Medicine Vienna, in Austria, and in tissue samples from prostate cancer patients.
“Most interestingly, inhibition of these enzymes stopped the growth of prostate cancer cells, suggesting that HTC could be a key target to develop new therapeutics for a variety of cancers, including prostate cancer,” said Ferbeyre.
Most key metabolic cycles were identified more than 50 years ago, but HTC remained hidden to researchers. “We found it by performing state-of-the art metabolomic analysis, the study of chemical processes of cell metabolism,” said co-author Ivan Topisirovic, a McGill researcher and medical professor.
The scientists were able to assemble the enzyme complex from purified proteins and obtain biophysical data about its composition. Their next step will be to generate a detailed high-resolution structure of the enzyme complex in order to design drugs able to modulate its functions.
About this study
“A hydride transfer complex reprograms NAD metabolism and bypasses senescence,” by Sebastian Igelmann et al., was published September 16, 2021 in Molecular Cell.
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Over the past decade, scientists have been exploring vaccination as a way to help fight cancer. These experimental cancer vaccines are designed to stimulate the body’s own immune system to destroy a tumor, by injecting fragments of cancer proteins found on the tumor.
So far, none of these vaccines have been approved by the FDA, but some have shown promise in clinical trials to treat melanoma and some types of lung cancer. In a new finding that may help researchers decide what proteins to include in cancer vaccines, MIT researchers have found that vaccinating against certain cancer proteins can boost the overall T cell response and help to shrink tumors in mice.
The research team found that vaccinating against the types of proteins they identified can help to reawaken dormant T cell populations that target those proteins, strengthening the overall immune response.
“This study highlights the importance of exploring the details of immune responses against cancer deeply. We can now see that not all anticancer immune responses are created equal, and that vaccination can unleash a potent response against a target that was otherwise effectively ignored,” says Tyler Jacks, the David H. Koch Professor of Biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.
MIT postdoc Megan Burger is the lead author of the new study, which appears today in Cell.
T cell competition
When cells begin to turn cancerous, they start producing mutated proteins not seen in healthy cells. These cancerous proteins, also called neoantigens, can alert the body’s immune system that something has gone wrong, and T cells that recognize those neoantigens start destroying the cancerous cells.