Sunday, December 04, 2022

Study using DNA analysis of sacrificial spider monkey suggests Mesoamerican diplomacy

Peer-Reviewed Publication

UNIVERSITY OF OKLAHOMA

LMAMR students 

IMAGE: UNIVERSITY OF OKLAHOMA STUDENTS WORK IN THE LABORATORIES OF MOLECULAR ANTHROPOLOGY AND MICROBIOME RESEARCH ANCIENT DNA LAB. view more 

CREDIT: PHOTO BY ROBIN SINGLETON

NORMAN, OKLA. – A multimethod archaeological study of a spider monkey sacrificed at Teotihuacàn, located approximately 25 miles from Mexico City, provides the earliest evidence of primate captivity and translocation in the Americas over 1,500 years ago.

Researchers at the University of Oklahoma’s Laboratories of Molecular Anthropology and Microbiome Research led the genetic analysis of the spider monkey’s skeleton. The OU team includes study co-authors Courtney Hofman, Ph.D., President’s Associates Presidential Professor in the Department of Anthropology, Dodge Family College of Arts and Sciences, with graduate student Robin Singleton and laboratory technician Karissa Hughes.

“Geoffrey’s spider monkeys are not found near Teotihuacàn today,” Hofman said. “Ancient DNA analysis of this spider monkey sought to identify the subspecies of the spider monkey, which can provide insight into ancient trade networks.”

“We were able to confirm that the spider monkey was most closely related to two endangered populations, the Mexican and the Yucatan spider monkey subspecies,” she added. “Using additional lines of evidence, including isotopic analysis, we hypothesized that this animal was of the Mexican subspecies, which today lives in parts of Mexico, Guatemala and Honduras. The presence of this animal in the central Mexican city of Teotihuacàn suggests that there was greater interaction with the Maya than previously understood and perhaps this spider monkey was a diplomatic gift.” 

The study, Earliest evidence of primate captivity and translocation supports gift diplomacy between Teotihuacan and the Maya, was published Nov. 21 in the journal Proceedings of the National Academy of Sciences and was featured in Science.

Nawa Sugiyama, assistant professor of anthropology at the University of California, Riverside, is the first author. In addition to the OU team, co-authors include researchers from Arizona State University; the Archéologie des Amériques in Paris, France; the Smithsonian Museum Conservation Institute; the RIKEN Institute in Kobe, Japan; and Washington State University.


Courtney Hofman, professor of anthropology at the University of Oklahoma, and Laboratories of Molecular Anthropology and Microbiome Research lab technician Karissa Hughes work in OU’s LMAMR ancient DNA lab.

CREDIT

Photo by Robin Singleton

University of Oklahoma graduate student Robin Singleton examines material from Teotihuacàn under a microscope in the Laboratories of Molecular Anthropology and Microbiome Research ancient DNA lab.

CREDIT

Photo by Courtney Hofman.

Discovery of antibody structure could lead to treatment for Crimean Congo Hemorrhagic Fever virus

Study provides insights into fighting broad range of pathogen’s viral strains

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - RIVERSIDE

RIVERSIDE, Calif. -- A research team led by the University of California, Riverside, has discovered important details about how therapeutically relevant human monoclonal antibodies can protect against Crimean Congo Hemorrhagic Fever virus, or CCHFV. Their work, which appears online in the journal Nature Communications, could lead to the development of targeted therapeutics for infected patients.  

An emerging zoonotic disease with a propensity to spread, CCHF is considered a priority pathogen by the World Health Organization, or WHO. CCHF outbreaks have a mortality rate of up to 40%. Originally described in Crimea in 1944–1945, and decades later in the Congo, the virus has recently spread to Western Europe through ticks carried by migratory birds. The disease is already endemic in Africa, the Balkans, the Middle East, and some Asian countries. CCHFV is designated as a biosafety level 4 pathogen (the highest level of biocontainment) and is a Category A bioterrorism/biological warfare agent. There is no vaccine to help prevent infection and therapeutics are lacking. 

Scott D. Pegan, a professor of biomedical sciences in the UCR School of Medicine, collaborated on this study with the United States Army Medical Research Institute of Infectious Diseases, or USAMRIID, which studies CCHFV because of the threat it poses to military personnel around the world. They examined monoclonal antibodies, or mAbs, which are proteins that bind to antigens — foreign substances that enter the body and cause the immune system to mount a protective response. 

In a previous publication, USAMRIID scientists Joseph W. Golden and Aura R. Garrison reported that an antibody called 13G8 protected mice from lethal CCHFV when administered post-infection. They provided Pegan with the sequence information for that antibody, clearing the way for UCR to “humanize” it and conduct further research.

“The USAMRIID study showed that the mouse mAb, 13G8, helps the immune system clear the infection,” Pegan said. “We knew 13G8 binds to a viral glycoprotein called GP38, but it wasn’t clear where that binding took place. So we analyzed the structure to gain an understanding of how it works and pinpoint exactly where the binding occurs. This knowledge sheds light on the potential of these mAbs to be effective against a broad range of CCHF viral strains.”

Members of Pegan’s research team were also able to obtain serum from patients who contracted CCHF in Turkey. The researchers isolated seven mAbs from a CCHFV survivor and identified two new antigenic sites on GP38. They then solved the structure of GP38 bound to one of the seven non-neutralizing human antibodies, in addition to 13G8. Knowledge of the structure of this complex can confer a clinical benefit as well, according to the authors. 

“This structural information further characterizes GP38 as an antigen of interest for vaccination studies, while also advancing mAb development toward CCHFV,” Garrison said. “The therapeutic role for non-neutralizing antibodies in preventing disease is becoming more evident for high-risk pathogens such as Ebola, Lassa, and Nipah virus.” 

Pegan explained that CCHFV has a tri-segmented RNA genome, consisting of a large, medium, and small segment. In 2006, GP38 was identified as a component of the medium fragment by the Special Pathogens Branch at the Centers for Disease Control and Prevention, or CDC, which also contributed to the Nature Communications study. The function of GP38 and its role in CCHFV infection remain unclear. 

“We know that targeting GP38 stops CCHFV’s progression, but no one is fully certain about how it works,” Pegan said. “We would like to know more about its mechanism of action so that specific and effective therapeutics can be developed.”

The research was funded by grants to Pegan and his CDC partner, Éric Bergeron, from the National Institutes of Health and the Department of Defense. Golden and Garrison were supported by the Military Infectious Diseases Research Program. 

Pegan, Garrison, and Bergeron were joined in the study by Elif Karaaslan, Jack McGuire, and David Gonzalez of UC Riverside; Ian A. Durie, Suzanne Enos, and Jarrod J. Mousa of the University of Georgia; Zahra R. Tehrani and Mohammad M. Sajadi of the University of Maryland School of Medicine; Teresa E. Sorvillo, Stephen R. Welch, Markus H. Kainulainen, Jessica R. Harmon, Jessica R. Spengler, and Christina F. Spiropoulou of the CDC’s Special Pathogens Branch; Joseph W. Golden of USAMRIID; Iftihar Koksal of Acibadem University Atakent Hospital, Turkey;  Gurdal Yilmaz, Sanaz Hamidi, and Cansu Albay of Karasdeniz Technical University School of Medicine, Turkey; and Hanife Nur Karakoc of Bitlis State Hospital, Turkey. 

About the University of California, Riverside:

The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment is more than 26,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual impact of more than $2.7 billion on the U.S. economy. More information.

About the U.S. Army Medical Research Institute of Infectious Diseases:

Since 1969, USAMRIID has provided leading edge medical capabilities to deter and defend against current and emerging biological threat agents. The Institute is the only laboratory in the Department of Defense equipped to safely study highly hazardous viruses requiring maximum containment at Biosafety Level 4. Research conducted at USAMRIID leads to vaccines, drugs, diagnostics, and training programs that protect both Warfighters and civilians. The Institute's unique science and technology base serves not only to address current threats to our Armed Forces but is an essential element in the medical response to any future biological threats that may confront our nation. More information.

University of Cincinnati research examines workplace stress in the aftermath of the COVID-19 pandemic

Certain professions report more stress than others

Peer-Reviewed Publication

UNIVERSITY OF CINCINNATI

Chronic stress is associated with a wide range of health disparities, but the examination of workplace stress has been minimal in many occupations.

A new study from the University of Cincinnati examined the impact of workplace stress and provided insights for organizations to explore ways to reduce workplace stress for a better and healthier working environment.

The study had two parts: a survey in which respondents described their experiences of workplace stress during the COVID-19 pandemic and a quantitative study using saliva cortisol as a biomarker of stress along with a stress diary to find out where and when workplace stress commonly occurred.

The first part of the study, published in the Annals of Work Exposures and Healthdetailed increased stress levels, stressor events and other perceptions of stress from at-risk workers during COVID-19.

“Stress is often overlooked in the workplace, and we tend to look at traditional health hazards like chemical exposure to gases and particles or physical hazards like falls, cuts and burns,” says Jun Wang, PhD, of the Department of Environmental and Public Health Sciences in the UC College of Medicine and faculty mentor on the study.

“Stress, even though not as ‘tangible’ as chemical or physical hazards, can deeply affect workers’ mental health and lead to workplace injury and illness. Workplace stress issues were amplified during COVID-19 because many people worked from home. Many health care professionals were also overloaded due to the increased number of patients and less resources.”

The UC research developed an in-depth, work-related stress survey that incorporated many aspects of work conditions, work context, work-life balance and the health of employer-employee relationships with a focus on COVID-19-related stressors. The cross-sectional survey was completed by 670 workers in a variety of clearly distinguished sectors, including manual labor, business settings, health care and education.

More than 50% of the participants reported experiencing an increased workload since the onset of the pandemic with some sectors, like health care, reporting an increased workload more frequently, at 80%. Around 55% of respondents believed they could be exposed to COVID-19 in their workplace, ranging from 52% of business/office service workers to 77% of health care workers, and this perception of COVID-19 exposure led as the greatest stressor.

“As workplaces navigate past the pandemic, occupational stress should be addressed head-on through providing expanded resources to assure work stress associated with future pandemics are mitigated appropriately,” says Wang. “Whether the stressor is associated with irregular shift work or psychosocial aspects, many of these stressors have the possibility to become exacerbated by external factors such as pandemics or economic downturns which we are experiencing right now.”

The second part of the study, published in the International Journal of Environmental Research and Public Health, found a relationship between occupational stress and increased salivary cortisol levels. For the study, 15 participants were recruited via email and social media. Each was given a kit containing a blank work stress diary, a sampling log, study protocol and nine saliva collection vials.

“As the body’s main stress hormone, cortisol is released each day, with levels typically highest in the morning and tapering off throughout the day,” says Thomas Gerding, PhD candidate and primary student investigator in this study. “Traditionally, cortisol-based stress research required [participants] to come to a clinic around noon and [have] their saliva collected by a professional. This method is not suitable to identify the fluctuation of cortisol throughout the day, and it is hard to correlate them to specific stressors such as workplace conflict and work-life balance issues.”

During three consecutive working days, participants were asked to document anything causing stress during working hours in the diary which included sections for occupation, date, time of day, intensity of stress on a scale of 0 to 5 (no stress to the highest level of stress), stress duration, situation description, triggering event, if applicable, and any emotional behavioral reaction. They were also asked to describe whether the day would be considered typical of their job.

“The whole idea of this project is to create a way for people to investigate their stress level by using this kit themselves, developing self-measures of saliva,” Wang says. “They collect the saliva in the tube, then they freeze it, and they also document what is likely the stressor event. If you feel stress, what is it? What is the nature of the stress?”

Wang says measuring cortisol changes may provide insights into types of occupational stressors and how these may be minimized. The goal of subsequent research in this area is to establish a measurable baseline for stress, with an emphasis on high stress occupations such as home health care workers or firefighters.

“In the future we will try to include a way to measure the baseline for each person so when they are comparing their stress level, they are comparing to their baseline,” Wang says.

“Stress is something that has been understudied in the past. A lot of people don’t take stress as critical as other aspects of the workplace environment. When people have stress or a mental health issue, like depression, a lot of times people don’t talk about those things. Moving forward, it is critical to build a healthier workplace with fewer hazards and less stress.”

This study is sponsored by the National Institute for Occupational Safety and Health (NIOSH) through various mechanisms, although the study conclusions do not necessarily represent the official stance of NIOSH. NIOSH’s largest research office is located several miles from the University of Cincinnati campus. In recent years, NIOSH has been closely collaborating with researchers at the University of Cincinnati on solving emerging workplace issues. 

 

New analysis finds pandemic didn’t dampen deforestation

Peer-Reviewed Publication

THE ALLIANCE OF BIOVERSITY INTERNATIONAL AND THE INTERNATIONAL CENTER FOR TROPICAL AGRICULTURE

Has deforestation accelerated due to the pandemic? 

IMAGE: DEFORESTATION GLOBALLY PROCEEDED MORE OR LESS AS EXPECTED FROM THE TRENDS ESTABLISHED OVER THE LAST 15 YEARS, ACCORDING TO A RECENT STUDY view more 

CREDIT: ALLIANCE OF BIOVERSITY AND CIAT / N.PALMER

Despite the massive upheavals in the first year of the COVID-19 pandemic, deforestation globally proceeded more or less as expected from the trends established over the last 15 years, according to a recent study from researchers at the Alliance of Bioversity International and CIAT.

In the paper “Has global deforestation accelerated due to the COVID-19 pandemic?” published in mid-November 2022, the researchers used historical deforestation data (2004–2019) from the Terra-i pantropical land cover change monitoring system to project expected deforestation trends for 2020.

Analysis of tree cover loss over time was used to determine whether deforestation observed in 2020 deviated from expected trajectories after the first COVID-19 cases were reported; both at the regional level for the Americas, Africa and Asia and at the country level for Brazil, Colombia, Peru, the Democratic Republic of the Congo and Indonesia.

“It was not particularly surprising to see little change,”

says Janelle Sylvester,  who is the corresponding author of the study and a Research Fellow at the Alliance.

She said that deforestation rates likely did not drastically change for many reasons. For one, it is probable that the complex dynamics driving deforestation before the pandemic persisted unimpacted by the lockdowns.

“For example, illegal deforestation in areas where there was minimal state (governmental) presence before the pandemic would likely continue during lockdowns,” she said. 

Moreover, she explained that “global-level macroeconomic forces related to changes in demand and supply paired with national economic stimulus packages could have balanced out economic pressures that were being placed on forests.”

Louis Reymondin, who co-leads the Digital transformation of the agri-food systems research theme for the Alliance of Bioversity International and CIAT also said that the finding wasn’t surprising, given that deforestation is heavily driven by livestock grazing and that demand for those products continued during the lockdowns in 2020.

“There were changes in food consumption habits, but usually it was towards processed foods and a reliance on industrialized agriculture,” he said, “The disruption needed to stop deforestation is about changing consumer behavior, changing the food system… and that's something that countries and governments and scientists are trying to push forward.”

Jonathan Céspedes, the lead author of the study, an Alliance of Bioversity and CIAT research assistant during the study and now a 2nd year Phd Student at Institut Polytechnique de Paris says that his task was to evaluate deforestation and COVID-19 data in order to determine possible relationships between both variables.

“It is key to take into account that the spatial scale of this study is global; therefore, the next stage is to evaluate sub-national and local scales, where probably the results may be different,” Céspedes said.

Sylvester said that to get a genuine snapshot of the impact, more research would be required, as national economic recovery efforts in response to the pandemic may have longer-term effects on deforestation that are not captured in this study limited to 2020.

“All in all we see that deforestation trends in most countries followed their expected trajectories; however, to really understand the effects of the pandemic on deforestation we will have to look at a longer time period, say three years or more, in order to understand how national economic recovery efforts impact forest cover,” Sylvester said.

The Alliance’s Role

Sylvester explained that the previous expertise of the Alliance was key in reaching these conclusions.

“The Alliance of Bioversity and CIAT has a great team working with the Terra-i deforestation monitoring system, their expertise working with these deforestation alerts contributed immensely to this study,” Sylvester said.

Augusto Castro-Nunez, the lead supervisor and a senior scientist for low emissions food systems at the Alliance Bioversity and CIAT said that the Alliance is well-known for its many years of experience monitoring forest cover changes.

“More recently the Alliance has developed the capacities to not only monitor the changes but to understand the underlying drivers behind them,” he said, “We have been publishing on this topic for many years focusing on conflict-affected settings like Colombia and more recently, we have been studying the food system drivers of deforestation with the FAO as a partner.”

 


  • Learn more by reading the paper.

Researchers discover root exudates have surprising and counterintuitive impact on soil carbon storage

Peer-Reviewed Publication

HARVARD UNIVERSITY, DEPARTMENT OF ORGANISMIC AND EVOLUTIONARY BIOLOGY

Chari_fig 4 

IMAGE: CONCEPTUAL DIAGRAM ILLUSTRATING THE EFFECTS OF EXUDATION RATE (A) AND COMPOSITION (B) ON MINERAL-ASSOCIATED ORGANIC MATTER (MAOM) FORMATION AND LOSS AS MEDIATED BY MICROBIAL BIOMASS CARBON (MBC). view more 

CREDIT: NIKHIL CHARI

Ecosystem ecology studies often focus on what’s happening to plants above ground, for instance exploring photosynthesis or water loss in leaves. But what is happening below the ground in plant roots is equally important when evaluating ecosystem processes.

In a new study in Nature Geoscience researchers in the Department of Organismic and Evolutionary Biology at Harvard University examined root exudates and their impact on soil carbon storage revealing surprising and counterintuitive results.

Root exudates are organic carbon compounds (such as simple sugars, organic acids, and amino acids) released from living plant roots into the soil. These small molecules can bind directly to soil minerals, making them important regulators of soil carbon formation and loss. Unlike plant litter (such as leaves and roots), which must be decomposed before it can affect the soil carbon pool, root exudates can have immediate effects on mineral-associated organic matter (MAOM), which contains long-cycling, “stable” soil carbon.

Several studies show that anthropogenically elevated atmospheric CO2 concentrations are likely to increase the rate of plant root exudation and change the chemical composition of root exudates. Lead author Nikhil R. Chari, Ph.D. candidate, and senior author Professor Benton N. Taylor tested how these changes may affect soil carbon by examining how changing the rate of root exudation and the composition of exudates  affected native soil-carbon dynamics in a temperate forest.

Chari and Taylor collected soil cores from Harvard Forest, a temperate hardwood forest in central Massachusetts, and incubated them directly in centrifuge tubes. They then fabricated three different carbon-13 root exudate “cocktails” of simple sugar, organic acid, and amino acid. They delivered the “cocktails” to the soil cores via “artificial roots”  at two different rates over a thirty-day period. Unlike other studies, Chari and Taylor did not use homogenized or artificial soils. Their sampling method preserved large amounts of heterogeneity in soil carbon and microbial communities present in the forest.

“We wanted to know if these mechanisms were having an effect at ecologically meaningful scales,” said Chari. “We used intact soil cores to test if the effect of root exudates would overcome the natural heterogeneity in the system.”

The researchers measured both initial and final carbon stocks in the cores. They found that contributions of root exudates to soil carbon were driven by contributions to the long-cycling MAOM fraction. MAOM are microscopic coatings on soil particles made mostly of the byproducts of bacteria and fungi. MAOM stays in the soil for decades meaning it can maintain carbon in soil for a very long time.

At higher rates of root exudation the MAOM carbon pool did not change even as root exudate contributions to MAOM increased. But at lower rates of root exudation Chari and Taylor observed net MAOM carbon accumulation, even though the exudate contributions were not as great.

“You would think that if you increase the rate of root exudation you would increase carbon input into the soil forming more soil carbon,” said Chari, “but we found instead an opposite effect that offset the increase in carbon.”

The researchers refer to this as the priming effect. Priming occurs when the input of new soil carbon prompts the decomposition of old soil carbon. Enhanced rates of root exudation appeared to increase rates of MAOM priming relative to rates of MAOM formation.

“First principles would suggest that the more carbon we push into the soil via exudation, the more carbon is going to accumulate in these MAOM fractions. When, in fact, that doesn't seem to be the case,” said Taylor. “In reality, you get more MAOM formation, but you also get more loss of it and it balances out. You don't actually get more carbon sticking around in the soil, even when you’re pushing more in.”

Chari and Taylor also found the different exudate compounds each had different effects on the soil carbon. Glucose (simple sugar) produced higher MAOM turnover both in formation and loss, but there was no net accumulation of MAOM. While succinic acid (organic acid) and aspartic acid (amino acid) drove lower rates of MAOM formation, but did result in a net MAOM carbon accumulation. Interestingly, the researchers found that amino acids had a particularly strong positive effect in increasing microbial biomass carbon formation, while organic acids did not. These findings again suggests the larger microbial community enhances the microbial priming effect. The results further validate that predicted increases in root exudation rates and a shift toward simple sugars caused by global change may reduce soil’s carbon storage capacity.

“These changes are happening ubiquitously below the soil surface, yet even tiny changes in this process can have huge implication for soil carbon storage,” said Taylor. “People know that processes in a leaf are important, but every root below our feet has a huge impact on carbon in the soil. And elevated CO2, warming, or other climate change drivers, could cause soil carbon loss to increase disproportionately to soil carbon formation.”

Going forward, Chari and Taylor continue to measure changes in the rate and composition of root exudates under elevated CO2 and warming in a variety of different ecosystems, including temperate forests, grasslands, and corn and soybean agricultural fields.

Intact soil cores were incubated in centrifuge tubes (blue caps) with artificial roots connected to a manual pump system delivering different exudate solutions to each core.

CREDIT

Nikhil Chari


JOURNAL

Nature Geoscience

Mom’s dietary fat rewires male and female brains differently

Excess fat triggers immune cells to overeat serotonin in the brain of developing male mice, leading to depression-like behavior

Peer-Reviewed Publication

DUKE UNIVERSITY

Microglia Sequesters Serotonin 

IMAGE: A MICROGLIA (IN MAGENTA) FROM A MALE MOUSE BORN TO A MOM ON A HIGH-FAT DIET, WHICH SEQUESTERS MORE BRAIN SEROTONIN (IN GREEN) THAN MALES WITH MOM’S EATING A TYPICAL LAB DIET. THE BLUE IS THE GLIA’S NUCLEUS. view more 

CREDIT: STACI BILBO LAB, DUKE UNIVERSITY

DURHAM, NC -- More than half of all women in the United States are overweight or obese when they become pregnant. While being or becoming overweight during pregnancy can have potential health risks for moms, there are also hints that it may tip the scales for their kids to develop psychiatric disorders like autism or depression, which often affects one gender more than the other.

What hasn’t been understood however is how the accumulation of fat tissue in mom might signal through the placenta in a sex-specific way and rearrange the developing offspring’s brain.

To fill this gap, Duke postdoctoral researcher Alexis Ceasrine, Ph.D., and her team in the lab of Duke psychology & neuroscience professor Staci Bilbo, Ph.D., studied pregnant mice on a high-fat diet. In findings appearing November 28 in the journal Nature Metabolism, they found that mom’s high-fat diet triggers immune cells in the developing brains of male but not female mouse pups to overconsume the mood-influencing brain chemical serotonin, leading to depressed-like behavior.

The researchers said a similar thing may be happening in humans, too.

People with mood disorders like depression often lose interest in pleasurable activities. For mice, one innately pleasurable activity is drinking sugar water. Since mice preferentially sip sugar water over plain tap when given the choice, Ceasrine measured their drink preference as an estimate for depression. Males, but not females, born by moms on a high-fat diet lacked a preference for simple syrup over tap water. This rodent-like depression suggested to Ceasrine that mom’s nutrition while pregnant must have changed their male offspring’s brain during development.

One immediate suspect was serotonin. Often called the “happy” chemical, serotonin is a molecular brain messenger that’s typically reduced in people with depression.

Ceasrine and her team found that depressed-like male mice from high-fat diet moms had less serotonin in their brain both in the womb and as adults, suggesting these early impacts have lifelong consequences. Supplementing mom’s high-fat rodent chow with tryptophan, the chemical precursor to serotonin, restored males’ preference for sugar water and brain serotonin levels. Still, it was unclear how fat accumulation in mom lowered serotonin in their offspring.

To get at this, the team investigated the resident immune cells of the brain: microglia.

Microglia are the understudied Swiss Army knives of the brain. Their jobs include serving as a security monitor for pathogens as well as a hearse to haul away dead nerve cells. Microglia also have ample space and appetites to consume healthy brain cells whole.

To see if microglia were overindulging in serotonin, Ceasrine analyzed the contents of their cellular “stomach”, the phagosome, with 3D imaging, and found that males born by moms on high-fat diets had microglia packed with more serotonin than those born to moms on a typical diet. This indicated that elevated fat accumulation during pregnancy somehow signals through the male but not female placenta to microglia and instructs them to overeat serotonin cells. How fat can signal through the placental barrier remained a mystery, though.

One thought was that bacteria were to blame.

“There's a lot of evidence that when you eat a high fat diet, you actually end up with endotoxemia,” Ceasrine said. “It basically means that you have an increase in circulating bacteria in your blood, or endotoxins, which are just parts of bacteria.”

To test if endotoxins could be the critical messenger from mom to enwombed males, the team measured their presence and found that, indeed, high-fat diets during pregnancy beefed up endotoxin levels in the placenta and their offspring’s developing brain. Ceasrine said this may explain how fat accumulation triggers an immune response from microglia by increasing the presence of bacteria, resulting in overconsumed brain cells in male mice.

To see whether this may be true of humans as well, Ceasrine teamed up with Susan Murphy, Ph.D., a Duke School of Medicine associate professor in obstetrics and gynecology, who provided placental and fetal brain tissue from a previous study. Just as the researchers observed in mice, they found that the more fat measured in human placental tissue, the less serotonin was detected in the brains of males but not females.

Bilbo and Ceasrine are now starting to work out how and why female offspring are impacted differently when mom amasses high levels of fat during pregnancy. Fat doesn’t lead to depression in female mice, but it does make them less social, perhaps due to an overconsumption of the pro-social hormone oxytocin, instead of serotonin.

For now, this research highlights that not all placentas are created equally. This work may one day help guide clinicians and parents in better understanding and possible treatment or prevention of the origins of some mood disorders by considering early environmental factors, like fat accumulation during gestation.

So, why would the placenta treat male and female fetuses differently? Ceasrine was initially stumped when a student asked a similar question after a talk she gave to Bilbo’s class. Bilbo laughed and reiterated the question. But now they think they have it figured out.

 “I was hugely pregnant at the time, and I was like, ‘Oh, wait. Pregnancy!’” Ceasrine recalled. “Men never have to carry a fetus, so they never have to worry about the kind of immune response of self versus non-self that you have to do when you're a woman and you carry a baby.”

Support for the research came from the US National Institutes of Health (F32HD104430, R01ES025549), the Robert and Donna Landreth Family Foundation, and the Charles Lafitte Foundation.

CITATION: “Maternal Diet Disrupts the Placenta-Brain Axis in a Sex-Specific Manner,” Alexis M. Ceasrine, Benjamin A. Devlin, Jessica L. Bolton, Lauren A. Green, Young Chan Jo, Carolyn Huynh, Bailey Patrick, Kamryn Washington, Cristina L. Sanchez, Faith Joo, A. Brayan Campos-Salazar, Elana R. Lockshin, Cynthia Kuhn, Susan K. Murphy, Leigh Ann Simmons, Staci D. Bilbo. Nature Metabolism, Nov. 28, 2022. DOI: 10.1038/s42255-022-00693-8

Organ donations, transplants increase on days of largest motorcycle rallies

Findings should serve as alarm to increase safety, prepare for higher demand for trauma care and transplant services

Peer-Reviewed Publication

HARVARD MEDICAL SCHOOL

The number of organ donations and organ transplants goes up markedly during large motorcycle rallies, according to a newly published analysis led by researchers at Harvard Medical School and Massachusetts General Hospital.

The research, which appears Nov. 28 in JAMA Internal Medicine, shows that in the regions where the seven largest motorcycle rallies were held throughout the United States between 2005 and 2021, there were 21 percent more organ donors per day, on average, and 26 percent more transplant recipients per day, on average, during these events, compared with days just before and after the rallies.

Large-scale motorcycle rallies attract hundreds of thousands of attendees, and previous studies have shown that these events are accompanied by increases in traumatic injuries and deaths from motor-vehicle crashes.

For the new study, the researchers wanted to know whether these events corresponded to increases in organ donation and transplantation in the regions where they were held.

The researchers posed several questions, including whether organ donations rose along with trauma-related fatalities. They did. Also, was there a difference in the quality of organs donated due to clinical or demographic differences in donors during rallies. There wasn’t.

“The spikes in organ donations and transplantations that we found in our analysis are disturbing, even if not entirely surprising, because they signal a systemic failure to avoid preventable deaths, which is a tragedy,” said study first author David Cron, HMS clinical fellow in surgery at Mass General. “There is a clear need for better safety protocols around such events.”

“At the same time, it is important for transplant communities in places where these events are held to be aware of the potential for increased organ donors during those periods. Organ donation is often called the gift of life, and we should make sure that we do not squander it and can turn any of these tragic deaths into a chance to potentially save other lives,” added Cron, who is also a research fellow at the Center for Surgery and Public Health at Brigham and Women’s Hospital, where he is part of a group interested in understanding how policy decisions and other factors, both inside and outside of the health care system, affect efforts to improve the supply of organs for transplantation.

Using data from the Scientific Registry of Transplant Recipients for deceased organ donors age 16 years and older involved in a motor vehicle crash and recipients of organs from those donors from March 2005 to September 2021, the researchers estimated changes in the incidence of donation and transplants in regions that hosted rallies.

Researchers analyzed records from 10,798 organ donors and 35,329 recipients in the regions where the featured motorcycle rallies take place. During the days on which rallies were held, there were 406 organ donors and 1,400 transplant recipients in regions near the events. During the four weeks before and after the rallies, there were 2,332 organ donors and 7,714 transplant recipients in those locations.

They compared the dates of rallies with the days before and after the rallies. To rule out the influence of other factors not related to bike rallies, the researchers also compared figures from the rally locations with other regions not affected by the rallies and then looked at trends in the rally regions at other times of the year.

They also compared the demographic and clinical characteristics of the donors and the quality of organs donated during rally and non-rally times. They found no significant differences.

Key characteristics of transplant recipients, such as how long they had been waiting for an organ and how severe their illness was at the time of transplant, were also similar whether there was a rally happening or not. This finding, the researchers noted, indicates that the increase in the number of organs available was not enough to relieve the critical shortage of donor organs that the nation faces, even for a brief period.

Cron also noted that the available data were not detailed enough to say whether the donors perished in motorcycle crashes or in passenger vehicles.

Bike rallies are generally large, crowded events that take place in rural areas or small towns with traffic infrastructure intended for much smaller populations and far less traffic, the researchers noted. This means that to increase overall safety for all motorists and pedestrians, event organizers should pay close attention to overall traffic management in addition to encouraging wearing of helmets and safe motorcycle operation.

The seven motorcycle rallies in the study each draw more than 200,000 visitors over the course of several days. Daytona Bike Week in Florida and the Sturgis Motorcycle Rally in South Dakota are 10-day events that each draw 500,000 visitors.

For the towns that hold the rallies and the people who attend, there are many economic and personal benefits. However, understanding all the possible consequences of an event can help organizers and participants plan better to minimize the risk for unwanted “side effects,” the researchers said.

The paper is the latest in a series by senior author Anupam Jena, the Joseph P. Newhouse Professor of Health Care Policy in the Blavatnik Institute at HMS, examining the often-unanticipated impacts on the health system of large-scale public events. Some of his previous work in this area includes studies that have found that firearm injuries drop nationwide during NRA conventions, that high-risk patients with certain acute heart conditions are more likely to survive than other, similar patients if they are admitted to the hospital during national cardiology meetings, and that people who suffer heart attacks or cardiac arrests in the vicinity of an ongoing major marathon are more likely to die within a month due to delays in transportation to nearby hospitals.

“Nothing in life is ever completely safe. Our priority should be to make risky events like motorcycle rallies as safe as they can be,” Jena said. “But it’s also critical to have a clear understanding of how these events impact the health of individuals and the health care systems that we all rely on so that we can give participants, event organizers, and policymakers the context and data they need to make smart choices.”

Additional authors included Charles Bray and Christopher Worsham of HMS and Joel Adler of Dell Medical School, University of Texas at Austin.

This study was supported by funding from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.