Publisher Health

Researchers led by Katsunori Tanaka at the RIKEN Cluster for Pioneering Research (CPR) in Japan and Hiromitsu Haba at the RIKEN Nishina Center for Accelerator-Based Science (RNC) have developed a new technique that has the potential to generically treat several kinds of cancer, with fewer negative side effects than currently available methods. Published on June 27 in Chemical Science, the proof-of-concept study showed that tumors in mice grew almost three times less and survival was 100% after just one injection of a compound that is designed to emit small amounts of alpha radiation from the inside of cancer cells, thus killing them but sparing healthy tissue.
The side effects of standard chemotherapy and radiation treatment can be devastating, and the eradication of all cancer cells is not guaranteed, especially when the cancer has already metastasized and spread throughout the body. Therefore, the goal of most research these days is to find a way to specifically target cancer cells so that treatments only affect tumors. Some targeted treatments do exist, but they cannot be applied to all cancers. “One of the greatest advantages of our new method,” says Tanaka, “is that is can be used to treat many kinds of cancer without any targeting vectors, such as antibodies or peptides.”
The new technique relies on basic chemistry and the fact that a compound called acrolein accumulates in cancer cells. A few years ago, Tanaka’s team used a similar technique to detect individual breast cancer cells. They attached a fluorescent compound to a specific type of azide—an organic molecule with a group of three nitrogen atoms (N3) at the end. When the azide and acrolein meet inside a cancer cell, they react, and the fluorescent compound becomes anchored to structures inside the cancer cell. Because acrolein is almost absent from healthy cells, this technique acted like a probe to light up cancer cells in the body.
In the new study, rather than simply detecting cancer cells, the team targeted those cells for destruction. The logic was fairly simple. Instead of attaching the azide to a fluorescent compound, they attached it to something that can kill a cell without harming surrounding cells. The chose to work with astatine-211, a radionuclide that emits a small amount of radiation in the form of an alpha particle as it decays. Compared to other forms of radiation therapy, alpha particles are a little more deadly, but they can only travel about one twentieth of a millimeter and can be stopped by a piece of paper. In theory, when astatine-211 is anchored to the inside a cancer cell, the emitted alpha particles should damage the cancer cell, but not much beyond.
Once the team figured out the best way to attach astatine-211 to the azide probe, they were able to perform a proof-of-concept experiment to test their theory. They implanted human lung-tumor cells into mice and tested the treatment under three conditions: simply injecting astatine-211 into the tumor, injecting the astatine-211-azide probe into the tumor, and injecting the astatine-211-azide probe into the bloodstream. The found that without targeting, tumors continued to grow, and mice did not survive. As expected, when the azide probe was used, tumors grew almost three times less and many more mice survived — 100% when it was injected into the tumor and 80% when injected into the blood.
“We found that just one tumor injection with only 70 kBq of radioactivity was extremely effective at targeting and eliminating tumor cells,” says Tanaka. “Even when injecting the treatment compound into the bloodstream, we were able to achieve similar results. This means we can use this method to treat very early-stage cancer even if we don’t know where the tumor is.” The fluorescent probe version of this technique is already being tested in clinical trials as a way of visualizing / diagnosing cancer at the cellular level. The next step is to find a partner and begin clinical trials using this new method to treat cancer in humans.

A study by researchers at the University of Vienna and the University of Veterinary Medicine Vienna shows that information from body postures plays a similarly important role for dogs as it does for humans. The results offer new insights into how dogs and humans perceive each other and their environment. They confirm that the temporal lobe plays a central role in social communication and perception. The study is currently published in the journal Communications Biology.
Humans and primates have brain regions in the temporal lobe that are specialised in perceiving faces and bodies. Dogs also possess a temporal lobe that evolved independently of the primate brain. In recent years, behavioural research has shown that dogs, like humans, are experts in perceiving facial expressions and bodily gestures such as hand signals. “Whether this behavioural expertise is also reflected in the dog brain was the content of our study. Only a few research groups can conduct comparative magnetic resonance imaging studies with dogs,” explains first author Magdalena Boch.
The research group led by Magdalena Boch, Claus Lamm and Ludwig Huber is one of currently only four in the world conducting magnetic resonance imaging (MRI) studies with pet dogs. They developed training protocols to accustom the dogs to the MRI environment gradually. The dogs are not sedated and can leave the MRI at any time.
The study with 40 human participants and 15 pet dogs now provided the first evidence that dogs, like humans, have a brain region in the temporal lobe that is specialised in the visual perception of body postures. In addition, further regions in the dog brain are equally involved in perceiving faces and bodies. In contrast to humans, however, this did not only affect visual brain regions. When dogs look at faces and bodies, there are also differences in activation in areas responsible for processing smells.
In humans, the authors additionally identified already known regions specialised exclusively in face perception. “We humans often focus on the face when communicating with others. Our results suggest that faces are also an important source of information for dogs. However, body postures and holistic perception seem to play a superior role,” Magdalena Boch explains.
The specialised brain regions were equally active in dogs when they looked at pictures of conspecifics or humans. This underlines the close bond between dogs and humans, says Ludwig Huber. “Dogs and humans may not be closely related, but they have been close companions for thousands of years. Therefore, comparing dogs and humans also gives us new insights into the so-called convergent evolution of social perception and information processing processes,” Claus Lamm concludes.

Researchers at the Centre for Genomic Regulation (CRG) in Barcelona and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association in Berlin reveal how cells accelerate changes to their identity, a process known as cell fate conversion.
The study, published today in the journal eLife, has implications for cancer research as the disease often arises from errors in cell fate decisions. The study could eventually lead to new methods of accelerating or manipulating the molecular mechanisms involved in the formation of cancer.
Central to the study is C/EBPα (CCAAT/enhancer-binding protein alpha), a protein that orchestrates the conversion of B lymphocytes to macrophages, another type of immune cell. C/EBPα is a transcription factor, a type of protein which binds to specific DNA sequences in the regulatory regions of genes to influence the rate of transcription, the first step that leads to the activation or silencing of protein expression. Transcription factors play a vital role in the transformation of one cell type to another during differentiation and development, as well as in the growth and function of cells.
Like many other proteins, C/EBPα is modified by enzymes, for example through the addition of a methyl group to specific amino acids. These modifications can have significant effects on interactions of the protein. The researchers found that when one specific arginine residue of C/EBPα is left unmethylated, it greatly accelerates the conversion process of B lymphocytes to macrophages.
The study also found that the methylation of this specific arginine residue is mediated by the enzyme Carm1. Previous research has shown that Carm1-deficient mice are resistant to induced forms of acute myeloid leukaemia. The researchers hypothesise that the mechanisms they uncover in the present study can explain why: the unmethylated version of C/EBPα is a stronger inducer of macrophage differentiation compared to its methylated counterpart. As macrophages are a non-dividing cell type, this could prevent the formation of cancer cells.
The researchers made the discovery while screening for C/EBPα mutants which affect the efficiency of cell fate conversion using human and mouse models. The location of the critical amino acid within C/EBPα was found when the authors tested a mutant form called C/EBPαR35A. This mutant dramatically accelerated the speed by which B cells could be turned into macrophages.
To induce a cell conversion, C/EBPα works by interacting with another transcription factor called PU.1, which itself is essential for the development of immune cells and is already expressed in B cells. C/EBPαR35A had a much higher interaction affinity with PU.1, increasing the speed by which the combination of the two proteins silence the genes associated with B cells and activate the genes associated with macrophages.
The methylation of C/EBPα is an example of an epigenetic mechanism. These are mechanisms which modify how the genome — the instruction manual inside every cell of the human body — is read. “Drugs that affect epigenetic mechanisms as described in the present study may indeed alter the function of transcription factors and correct cells that went astray, such as seen in cancer and leukaemia,” says Dr. Achim Leutz, senior author from the Max-Delbrück-Center.
“In this novel mechanism PU.1 is triggered by C/EBPα to switch from a B cell regulator into a macrophage regulator, an elegant ‘on-off’ mechanism that ensures the faithful formation of a mature cell type, avoiding the formation of ‘confused’ cells often seen in blood cancers. Therefore, drugs might be found that target this mechanism to correct such defects” adds Dr. Leutz.
According to the authors of the study, much remains unknown about what determines the speed and directionality of cell fate decisions and their new work suggests that the two processes are two sides of the same coin. For instance, how do stem cells sequentially transform into the many different types of cells in the body? Better understanding how cells change their identity and how to manipulate the process might have applications from regenerative medicine to improving the efficacy of drugs against cancer.
The research was led by a joint collaboration between the Centre for Genomic Regulation in Barcelona, the Max Delbrück Center for Molecular Medicine in Berlin and the University of Pennsylvania in Philadelphia. The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness, the Catalan Agency of Research and Universities, a 4D-Genome European Research Council Synergy grant, by funds from the Max-Delbrueck-Center, and the United States National Institute of Health.

Studies of mammalian evolution often rely on the analyses of teeth, which are the best-preserved parts of fossilized skeletons. Tooth morphology and the composition of enamel — the most mineralized tissue of the body — constitute important criteria for speciation events that occurred over 200 million years of evolution. These evolutionary adaptations, which are linked to genetic modifications, have contributed to the extensive diversification of cell types in animals.
A team of researchers from the Center of Dental Medicine at the University of Zurich has identified the Notch pathway as the key gene network that is responsible for changes in tooth shape and enamel composition during evolution. The Notch pathway is an ancient, evolutionary conserved signaling mechanism that controls cell-fate decisions and proper morphogenesis of most organs, including teeth.
The evolution of teeth depends on Notch signaling
Using genetically modified mouse models, the research team of Thimios Mitsiadis, professor of oral biology at the Center of Dental Medicine at UZH, analyzed the effects of the Notch-ligands in teeth. Absence of those ligand molecules affected tooth morphology and enamel formation due to the alteration of numerous significant morphogenetic genes. Deregulation of the Notch pathway reverted the evolutionary cascade, thus generating less complex dental structures that are more reminiscent of the enameloid of fishes rather than that of mammalian enamel.
According to first author Mitsiadis, the study sheds new light on the Notch pathway as one of the crucial components for dental shape and enamel variations in evolution. “We hypothesize that the evolution of teeth depends on Notch signaling for the generation of new dental cell types from already existing primitive dental cell types, thus allowing the formation of more complex and unique dental structures such as tooth enamel,” Mitsiadis said.
Enamel malformations in humans
The correlation between Notch molecules and the generation and/or maintenance of distinct dental cell types could represent a general mechanism underlying the evolution of specialized cell types in mammals. “In teeth, deregulation of Notch signaling initiates the suppression of specific dental cell types that were acquired during evolution. Loss of these cells leads to the generation of enamel malformations and tooth morphological alterations,” Mitsiadis concludes. Modelling of these changes allows predictions of how Notch-associated mutations in humans could affect the morphology and enamel of their teeth.

Recurrent bouts of systemic lupus erythematosus, marked by the body’s immune system attack of its own tissues, closely tracked with measureable upticks in growth in the gut of a certain species of bacteria.
New research from NYU Grossman School of Medicine shows that bacterial blooms of the gut bacterium Ruminococcus blautia gnavus occurred at the same time as disease flare-ups in five of 16 women with lupus of diverse racial backgrounds studied over a four-year period. Systemic lupus erythematosus involves damaging inflammation, especially in the kidneys, but also in joints, skin, and blood vessels. Four of these study patients with R. gnavus blooms had severe cases of the most common and kidney-specific form of the disease, lupus nephritis, while one had a severe example of lupus involving inflammation in multiple joints.
Publishing in the Annals of Rheumatic Diseases online June 27, the team’s analysis of these lupus patients’ gut bacterial blooms identified 34 genes that already had established links to the bacterium’s growth in people with inflammation. While the specific causes of lupus, which affects as many as 1.5 million Americans, remain unknown, many experts suspect that bacterial imbalances trigger inherited genetic factors responsible for the disease.
This study also investigated how tightly these patients’ immune system antibodies bonded to structures in the bacterial wall, much like they would an invading virus. These antibodies showed a strong affinity to specific bacterial lipoglycan molecules that are known triggers of inflammation. These lipoglycans were found to be common in R. gnavus strains in lupus patients but not in healthy people. Antibodies are a major cause of the body damage in this disease, and this diagnostic antibody response, the researchers say, highlights the important role played by R. gnavus in the autoimmune disease.
“Our findings provide the strongest evidence to date that silent growths of Ruminococcus blautia gnavus are tied to active serious renal disease in lupus patients,” said study lead investigator Doua Azzouz, PhD.
“Interestingly, our study also established this common bacterial link among a racially diverse group of females with varying forms of lupus,” said Azzouz, a postdoctoral researcher in the Department of Medicine at NYU Langone Health. Lupus is more common in women than in men, and the disease affects more Blacks, Hispanics, and Asians than Whites.

“Our goal is to use our growing understanding of the biological pathways that underpin the disease to develop new treatments that prevent or treat flares for all forms of lupus,” said study senior investigator and immunologist Gregg Silverman, MD.
“Such future treatments for lupus, especially lupus nephritis, could potentially decrease the use of drugs designed to dampen the immune system and instead promote the use of less-toxic antibacterial agents, probiotics or dietary regimens that prevent imbalances such as Ruminococcal blooms in the local gut bacterial population, or microbiome,” said Silverman, the Mamdouha S. Bobst Professor of Internal Medicine in the Departments of Medicine and Pathology at NYU Langone Health.
Previous research by Silverman’s team showed that R. gnavus blooms weaken the gut wall barrier, prompting bacterial leakages that in turn trigger inflammatory and overactive immune responses.
Silverman, who also serves as associate director of rheumatology at NYU Langone, says the team plans to extend the current research to more patients at other medical centers. The team also has plans for further experiments in mouse models of lupus to see how R. gnavus colonization triggers lupus and whether in mice bred to develop lupus-like symptoms R. gnavus blooms speed up or otherwise affect the severity of flares and inflammation.
The researchers say they also want to conduct experiments on various lipoglycan molecules from different R. gnavus strains to see if any particular part of the molecular structure is key to triggering inflammation or if other lipoglycans also prompt an immune response tied to lupus or other diseases of the gut, including Crohn’s.
For the study, researchers used stool and blood samples from lupus patients being treated at NYU Langone. All study participants were being closely monitored for disease flare-ups. Test results were compared with those of 22 female volunteers of similar age and racial background who did not have lupus and were otherwise healthy.
As an autoimmune disease, systemic lupus erythematosus can lead to widespread inflammation and long-term tissue damage in affected organs. According to researchers, about half of patients develop lupus nephritis, of whom one-quarter are likely to experience end-stage renal disease that may require regular blood dialysis and even kidney transplantation.
Funding support for the study was provided by National Institute of Health grants UL1TR000038, P30CA016087, R01AR42455, P50AR070591, and HHSN272201400019C. Additional funding support was provided by the Lupus Research Alliance, the Judith and Stewart Colton Autoimmunity Center at NYU Langone, and the P. Robert Majumder Charitable Trust.
Besides Silverman, other NYU Langone researchers involved in this study are Ze Chen, Peter Izmirly, Lea Ann Chen, Zhi Li, Chongda Zhang, Adriana Heguy, Davis Mieles, Kate Trujillo, Alejandro Pironti, Gregory Putzel, David Fenyo, and Jill Buyon. Other study co-investigators are Dominik Schwudke and Nicolas Gisch, at the Leibniz Lung Center in Borstel, Germany; and Alexander Alekseyenko at the Medical University of South Carolina in Charleston.

Cambridge scientists have identified a signature in the blood that could help predict how well an individual will respond to vaccines. The discovery, published today in Nature Communications, may explain why, even among vulnerable patient groups, some individuals have better responses to vaccines than others.
During the COVID-19 pandemic, it has become clear that some patients are better protected by vaccination than others. Many studies have shown that SARS-CoV-2 vaccines are less effective in people with weakened immune systems, but also that this effect is not uniform.
Vaccination involves priming the immune system to look for — and get rid of — invading pathogens, such as viruses and bacteria. In part, this involves stimulating the production of antibodies uniquely programmed to identify a particular invader. These antibodies are themselves produced by a type of immune cell known as a B cell.
One specific subset of B cells is known as age-associated B cells (ABCs). While, on average, less than one in 20 of a healthy individual’s B cells is an ABC, the proportion gradually increases as we get older. The reasons for this increase are not yet fully understood, but may include previous infections. Certain people with weakened immune systems accumulate ABCs still faster.
A team from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge, led by Dr James Thaventhiran, examined ABCs from two very different patient groups — one composed of people with an inherited condition that impairs the activity of their immune systems and a second group composed of cancer patients taking immunotherapy drugs — as well as from healthy individuals.
Emily Horner, from Thaventhiran’s lab, explained the aim of this research: “By looking at patients’ B cells, we hoped to learn how we could stratify vulnerable patients — in other words, work out whether some patients were at greater risk from infection, even after vaccination, than others.”
The researchers measured the relative proportion of ABCs compared to healthy B cells, and used a technique known as single cell RNA sequencing to look in detail at the activity of cells. They also teamed up with Dr Nicholas Matheson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, to test how these factors influenced the ability of a vaccinated individual’s immune system to neutralise live SARS-CoV-2 virus.

Dr Yam-Puc, also from the MRC Toxicology Unit, said: “What we found, much to our surprise, was that the age-associated B cells in these very different groups looked the same. The key difference was in the amount of these cells — the greater the proportion of ABCs in an individual’s blood, the less effective that individual was post-vaccination at neutralising the virus.”
This could help explain the variability seen within particular patient groups in responses to the vaccine: people with fewer ABCs are likely to respond better to vaccines.
Although the researchers examined ABCs in the context of responses to the SARS-CoV-2 vaccine, they believe that this phenomenon will almost certainly apply more widely, for example to the annual influenza vaccine.
Dr Pehuén Pereyra Gerber, who performed the experiments with live SARS-CoV-2 virus in Matheson’s lab, added: “Looking at blood levels of ABCs could tell us that person A should respond well to a vaccine, while person B might need a stronger vaccine or to be prioritised to receive a booster.”
Thaventhiran added: “Ultimately, this research could lead to the development of a clinical test to predict vaccine efficacy for immunodeficient patients, and for the population more generally.”
The research was funded by the Medical Research Council, the Medical Research Foundation, and the Evelyn Trust.

People who have just one or two drinks per day are not protected against endocrine conditions such as obesity and type 2 diabetes, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Alcohol consumption is a significant public health concern because it is related to many medical conditions such as diabetes, obesity, liver conditions and heart disease. While it is widely accepted that excessive alcohol consumption causes a wide range of health issues, whether modest alcohol consumption has beneficial health effects remains controversial.
“Some research has indicated that moderate drinkers may be less likely to develop obesity or diabetes compared to non-drinkers and heavy drinkers. However, our study shows that even light-to-moderate alcohol consumption (no more than one standard drink per day) does not protect against obesity and type 2 diabetes in the general population,” said Tianyuan Lu, Ph.D., from McGill University in Québec, Canada. “We confirmed that heavy drinking could lead to increased measures of obesity (body mass index, waist-to-hip ratio, fat mass, etc.) as well as increased risk of type 2 diabetes.”
The researchers assessed self-reported alcohol intake data from 408,540 participants in the U.K. Biobank and found people who had more than 14 drinks per week had higher fat mass and a higher risk of obesity and type 2 diabetes.
These associations were stronger in women than in men. No data supported the association between moderate drinking and improved health outcomes in people drinking less than or equal to seven alcoholic beverages per week.
“We hope our research helps people understand the risks associated with drinking alcohol and that it informs future public health guidelines and recommendations related to alcohol use,” Lu said. “We want our work to encourage the general population to choose alternative healthier behaviors over drinking.”
The other authors of this study are Tomoko Nakanishi and Satoshi Yoshiji of the Jewish General Hospital and McGill University in Québec, Canada, Kyoto University in Kyoto, Japan, and the Japan Society for Promotion of Science in Japan; Guillaume Butler-Laporte and Celia Greenwood of the Jewish General Hospital and McGill University; and J. Brent Richards of the Jewish General Hospital, Prime Sciences Inc. in Québec, Canada, McGill University, and King’s College London in London, U.K.
The study received funding from the Fonds de Recherche du Québec — Santé, the Canadian Institutes of Health Research, McGill University, the Lady Davis Institute for Medical Research, the Fondation de l’Hôpital Général Juif, the Canadian Foundation for Innovation, Génome Québec, the Foundation for the National Institutes of Health, the Public Health Agency of Canada, Cancer Research UK, and the Japan Society for the Promotion of Science.

As we age, our bodies change and degenerate over time in a process called senescence. Stem cells, which have the unique ability to change into other cell types, also experience senescence, which presents an issue when trying to maintain cell cultures for therapeutic use. The biomolecules produced by these cell cultures are important for various medicines and treatments, but once the cells enter a senescent state they stop producing them, and worse, they instead produce biomolecules antagonistic to these therapeutics.
While there are methods to remove older cells in a culture, the capture rate is low. Instead of removing older cells, preventing the cells from entering senescence in the first place is a better strategy, according to Ryan Miller, a postdoctoral fellow in the lab of Hyunjoon Kong (M-CELS leader/EIRH/RBTE), a professor of chemical and biomolecular engineering.
“We work with mesenchymal stem cells, that are derived from fat tissue, and produce biomolecules that are essential for therapeutics, so we want to keep the cell cultures healthy. In a clinical setting, the ideal way to prevent senescence would be to condition the environment that these stem cells are in, to control the oxidative state,” said Miller. “With antioxidants, you can pull them the cells out of this senescent state and make them behave like a healthy stem cell.”
While treating the cells with antioxidants can delay senescence, current methods of antioxidant delivery have many shortcomings, including large variation in amount of drug release over time and between cells. However, a recently published study by the labs of Kong and Hee-Sun Han (GNDP/IGOH), an assistant professor of chemistry, with Miller as first author, describes a new method of delivering antioxidants to stem cells that is reliable, long-lasting, and minimizes variation.
The new method utilizes antioxidants in the form of polymer-stabilized crystals. Traditional methods grow crystals within reactors, but using microfluidics, a technology that allows researchers to work with incredibly small amounts of fluid, the researchers can create crystals that are all the same size and dosage, minimizing variation in drug release between cells. “With microfluidics, each drop functions as a small reactor, such that we can get small, similar-sized, individual crystals, which minimizes variation in drug release rate.” said Miller. Furthermore, the crystals dissolve at a slower rate than traditional methods, making the release of the drug uniform over time, and increasing the duration of the drug’s effectiveness.
“We learned that the narrow variation in the drug’s release profile is really important,” explained Han. “When you add drugs that dissolve in water, there is this bursting period where a lot of is dissolves in the liquid at once, and not much later. But the crystal allows this uniform, extended release, which helps maintain the tight range of optimal concentrations that are needed.”
“When typical antioxidants are put into water or biological fluid, they lose their vital activity within six hours,” described Kong. “But the new antioxidant crystal remains bioactive for at least two days, so we can actually extend the duration of the drug, and also reduce the frequency with which we have to add antioxidants to the cell culture media. This minimizes the variation in the type of the biomolecules the stem cells are generating and improves the reproducibility of the product, which is one of the biggest challenges in biomanufacturing at the moment.”
Increased duration of the drug’s efficacy means that stem cell cultures can be kept out of the senescence state for longer, which leads to a larger harvest of the needed biomolecules for therapeutics. Miller also says this method could be used for patient-derived stem cell treatments, where the biomolecules from a patient’s own body are used to help with various tissue ailments, such as injuries or disease.
“When we use biomolecules from donors instead of the patient, that can have a host effect,” explained Miller. “Ideally, we would harvest stem cells from the patient that we’re treating, grow them in a bioreactor, and harvest those biomolecules for that therapeutic. This works well for someone who is 20, but if we envision an elderly patient, they’re going to have a high population of these senescence cells, that are not going to be secreting the therapeutically relevant biomolecules. If we can pull those cells out of that state, and make them behave like a healthy cell, we can get a much larger load of therapeutically relevant biomolecules for the patient.”
The team says that while they want to continue to improve the biomanufacturing process, there are already many potential uses for this methodology besides just controlled delivery of antioxidants to stem cell cultures. Most cells experience senescence, so this technique could be applied to other cell cultures important in medicine and therapeutics. Furthermore, the crystals could be used to deliver sustained and controlled levels of antioxidants, or potentially other drugs, directly into the target tissue of a patient.
“I think the beauty here is that this is a technology development paper, so this can be applied to various hydrophilic drugs, disease models, and methods applications,” said Han. “We’re showing that we can maintain a sustained release of this drug at a relatively constant rate for an extended period of time. There are a lot of exciting studies and directions that we can go with this technology.”

A new study of a brain region called the rostro-medial prefrontal could potentially advance diagnosis and therapies for Borderline Personality Disorder (BPD). Entitled “Rejection Distress Suppresses Medial Prefrontal Cortex in Borderline Personality Disorder,” the research appears in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.
Researchers from The City College of New York, Columbia University, and New York State Psychiatric Institute led by CCNY psychologist Eric A. Fertuck discovered that the rostro-medial prefrontal specifically becomes more active when people are rejected by others at greater rates. However, individuals with BPD — characterized by interpersonal sensitivity to rejection and emotional instability — do not display rostro-medial prefrontal cortex activity when rejected.
The brain reacts with rostro-medial prefrontal activity to rejection as if there is something “wrong” in the environment. This brain activity may activate an attempt to try to restore and maintain close social ties to survive and thrive. This region of the brain also is activated when humans try to understand other peoples’ behavior in light of their mental and emotional state.
“Inactivity in the rostro-medial prefrontal cortex during rejection may explain why those with BPD are more sensitive and more distressed by rejection. Understanding why individuals with this debilitating and high risk disorder experience emotional distress to rejection goes awry will help us develop more targeted therapies for BPD,” said Fertuck, associate professor in CCNY’s Colin Powell School for Civic and Global Leadership, and the Graduate School, CUNY.
On the significance of the study, Fertuck noted that while previous findings in this area have been mixed, “what we’ve done is improve the specificity and resolution of our rejection assessment, which improves on prior studies.”
Research continues with several investigations underway examining the role of social rejection in different mental health problems including post-traumatic stress disorder, depression, and social anxiety.
Fertuck heads the Social Neuroscience and Psychopathology (SNAP) lab in the Colin Powell School. The lab advances a collaborative program of research at the interface of the clinical understanding of Borderline Personality Disorder and related psychopathology, psychotherapy research, experimental psychopathology, and social neuroscience.

What people say they’ve eaten and what they’ve actually eaten are often two very different lists of foods. But a new technique using DNA barcoding to identify the plant matter in human feces may get at the truth, improving clinical trials, nutrition studies and more.
Building on earlier studies that attempted to compare DNA found in feces with reported diets, researchers in the lab of Lawrence David, an associate professor of molecular genetics and microbiology in the Duke School of Medicine, have developed a genetic marker for plant-based foods that can be retrieved from poop.
“We can go back after the fact and detect what foods were eaten,” said Brianna Petrone, PhD, an MD/PhD student who led the project.
The marker is a region of DNA plants use to power chloroplasts, the organelle that converts sunlight into sugars. Every plant has this genomic region, called trnL-P6, but it varies slightly from species to species. In a series of experiments, they tested the marker on more than 1,000 fecal samples from 324 study participants across five different studies, about twenty of whom had high-quality records of their diet.
In findings appearing June 27 in the Proceedings of the National Academy of Sciences, the researchers show that these DNA markers can indicate not only what was consumed, but the relative amounts of certain food species, and that the diversity of plant DNA found in feces varies according to a person’s diet, age, and household income.
David’s lab relied on a reference database of dietary plants that contains markers for 468 species typically eaten by Americans to connect versions of trnL-P6 detected in poop to specific plant sources. After some tweaking, their barcode was able to distinguish 83 percent of all major crop families.

Petrone said the subset of crop families that could not currently be detected tended to be consumed in other parts of the world. The lab is now working to add crops such as pearl millet and pili nuts to their database.
They also haven’t tracked meat intake yet, though the technology is capable of that as well, David said. “That relative ratio of plant to animal intake is probably one of the most important nutritional factors we might look at.”
The scientists first tried the marker out on fecal samples from four individuals in a weight loss intervention where they knew exactly what study participants had been fed a day or two before. Knowing the patients had been given a dish called mushroom wild rice pilaf for example, they looked for the markers of its components: wild rice, white rice, portobello mushrooms, onion, pecans, thyme, parsley and sage.
In this and a second intervention group, they found that barcoding could not only identify the plants, it also could identify relative amounts consumed for some kinds of plants. “When big portions of grains or berries were recorded in the meal, we also saw more trnLfrom those plants in stool,” Petrone said.
Then they looked at samples from 60 adults who had taken part in two studies of fiber supplementation and kept track of what they were eating with surveys. The number of plants detected by trnL was in good agreement with dietary diversity and quality estimated from participants’ survey responses.

Next, they applied the barcoding to a study 246 adolescents with and without obesity with diverse racial, ethnic, and socioeconomic backgrounds. There was only a minimal record of diet in this cohort.
“Dietary data collection was challenging because some traditional surveys are 140 pages long and take up to an hour to fill out, families are busy, and a child might not be able to fill it out alone,” David said. “But because they had banked stool, we were able reanalyze those samples and then gather information about diet that could be used to better understand health and lifestyle patterns between kids. What really struck me was that we could recapitulate things that were known as well get new insights that might not have been as obvious.”
They found 111 different markers from 46 plant families and 72 species in the adolescents’ diet. Four kinds of plants were eaten by more than two thirds of subjects: wheat, found in 96 percent of participants, chocolate (88%), corn (87%) and the potato family (71%), a group of closely related plants that includes potato and tomatillo.
David said the barcode isn’t able to distinguish individual members of the cabbage family — the brassica — such as broccoli, Brussels sprouts, kale, and cauliflower, which are closely related.
Still, the large adolescent cohort showed that dietary variety was greater for the higher-income study participants. The older the adolescents were however, the lower their intake of fruits, vegetables and whole grain foods, potentially because of a known pattern of older children eating with their families less often.
David said the barcode is readily able to identify the diversity of plants found in a sample as a proxy for dietary diversity, a known marker of nutrient adequacy and better heart health.
David said that in each of these cohorts, the genomic analyses had been carried out on samples that had been collected years in the past, so the technique opens up the possibility of reconstructing dietary data for studies that have already been finished.
The authors think the new methodology should be a boon for all sorts of studies of human nutrition. “We are limited in how we can track our diets, or participate in nutrition research or improve our own health, because of the current techniques by which diet is tracked,” David said. “Now we can use genomics to help gather data on what people eat around the world, regardless of differences in age, literacy, culture, or health status.”
The team anticipates extending the technique to studies of disease across the globe, as well as monitoring food biodiversity in settings facing climate instability or ecological distress.
Funding for this work came from the National Institute of Diabetes and Digestive and Kidney Diseases (grants 5R24DK110492-05 and 5R01DK116187-05), the Burroughs Wellcome Fund Pathogenesis of Infectious Disease Award, the Duke Microbiome Center, the Springer Nature Limited Global Grant for Gut Health, the Chan Zuckerberg Initiative, the Triangle Center for Evolutionary Medicine, the Integrative Bioinformatics for Investigating and Engineering Microbiomes Graduate Student Fellowship, and the Ruth L. Kirschstein National Research Service Award to the Duke Medical Scientist Training Program. This work used a high-performance computing facility partially supported by grants from the North Carolina Biotechnology Center (2016-IDG-1013 and 2020-IIG-2109).