Chemists are on the hunt for the other 99 percent

New mass spectrometry combo offers promise for tapping nature’s unknown chemical universe

Peer-Reviewed Publication

DOE/PACIFIC NORTHWEST NATIONAL LABORATORY

 

IMAGE: ADAM HOLLERBACH WITH A SLIM DEVICE CREATED AT PACIFIC NORTHWEST NATIONAL LABORATORY. view more 

CREDIT: PHOTO BY ANDREA STARR | PACIFIC NORTHWEST NATIONAL LABORATORY

The universe is awash in billions of possible chemicals. But even with a bevy of high-tech instruments, scientists have determined the chemical structures of just a small fraction of those compounds, maybe 1 percent.

 

Scientists at the Department of Energy’s Pacific Northwest National Laboratory (PNNL) are taking aim at the other 99 percent, creating new ways to learn more about a vast sea of unknown compounds. There may be cures for disease, new approaches for tackling climate change, or new chemical or biological threats lurking in the chemical universe.

 

The work is part of an initiative known as m/q or “m over q”—shorthand for mass divided by charge, which signifies one of the ways that scientists measure chemical properties in the world of mass spectrometry.

 

“Right now, we can take a sample from soil, where, depending on soil type, there may be thousands of chemical compounds in just a teaspoon’s worth,” said Thomas Metz, who leads the m/q Initiative. “And we don’t know what most of them are in terms of their chemical structures. We simply have no idea what’s in there.”

 

Scientists typically rely on reference libraries that contain information about thousands of molecules to identify substances. Researchers sort their samples from soil, the body, or elsewhere and compare what they have measured experimentally to what’s in the library. While that’s helpful, it limits scientists to only structurally identifying molecules that have been seen before—for example, through analysis of standard compounds purchased from chemical suppliers.

 

m/q scientists are taking aim at the other 99 percent that haven’t been identified—yet.

 

In the latest development, a team led by scientist Adam Hollerbach has combined two high-resolution instruments into one system to size up molecules in unprecedented detail. The results were published online June 12 in the journal Analytical Chemistry.

 

Now, scientists can make several important measurements about chemical compounds in one experiment, gaining important information faster, more conveniently, and more accurately than before.

 

Hollerbach’s technique applies to ions—molecules that have either a positive or negative charge. That makes them easier to control and possible to detect using mass spectrometry.

 

Mass spectrometry: tool of the ion whisperers

Like the people who study them, ions have many features that distinguish one from another. In people, weight, hair color, size, shape, eye color, and many other characteristics help us know who’s who. For ions, identifying characteristics include mass, shape, size, electric charge, and chemical composition. Those not only serve as identifiers but also as guides to the associated molecules’ behavior—clues to their potential to cure disease or sop up pollutants, for example.

 

That understanding should help the efforts of scores of scientists at PNNL who focus on understanding the effect of microbes on climate. Microbes play a key role in transforming elements like carbon into other forms that are important for the planet. Their impact on warming or cooling the planet is mighty. But scientists have much to learn.

 

“There may be millions of microbes in just a gram of soil, and we don’t know who most of them are or what they do. There’s a lot of discovery still to happen,” said Metz. “From the viewpoint of challenging science, it’s either a worst-case scenario or one of our greatest opportunities, depending on how you look at it.”

m/q scientists are seizing the opportunity. Instead of framing their questions within the relatively small number of compounds that can be identified in conventional mass spectrometry measurements, they’re trying to leapfrog current limitations and create a whole new way of identifying what is unknown today. It’s a bit like when a new telescope is deployed and reveals several distinct stars where before, just one blurry hodgepodge of celestial bodies was visible.

 

The work is both experimental, putting molecules through their paces in the laboratory, and on computers, where scientists model what they are seeing and predict what they will likely see.

 

In the experiments described in the Analytical Chemistry paper, Hollerbach and colleagues made sensitive measurements of peptides and lipids. The experiments combined two instruments with similar names but that provide different details about ions. Both are used in mass spectrometry, a field whose history is interwoven with discoveries by PNNL scientists.

 

The first instrument is a mass spectrometer, which measures an ion’s mass, electric charge, and how the ion breaks apart. In this study, the team used an Orbitrap developed by Thermo-Fisher Scientific. Such instruments sort molecules of different masses well, but two molecules with the same mass are difficult to separate. Think of two people, each weighing 180 lbs.—one is tall and thin while the other is short and stocky. On a scale alone, they would be impossible to separate.

 

A SLIM approach: ion mobility spectrometry brings hefty results

The second instrument is known as SLIM: structures for lossless ion manipulations. SLIM, created by PNNL scientist Richard D. Smith and colleagues, is an ion mobility spectrometer that measures an ion’s size and electric charge.

 

SLIM, which is about the size of a laptop and stands at just one-quarter of an inch thick, is a hothouse of molecular activity. Dozens of long, winding paths transform the small device into a 42-foot-long molecular racetrack, with ions that are controlled tightly by electric fields racing round and round an oval obstacle course.

 

The “obstacles” are other, known molecules such as helium or nitrogen molecules. As the ions under study race through the SLIM device, they navigate around or through the other molecules, tumbling and swerving much like a football running back runs through and around opposing blockers. The term “ion mobility spectrometry” truly captures the action.

 

By recording how long it takes for the ions to complete the course—how deftly they navigate the blocking ions—scientists learn all kinds of things about ions’ shape and size. That information, which isn’t available from a standard mass spec instrument, is combined with data about the ion’s mass, electric charge, and fragmentation pattern. Altogether, the data yields the ion’s collision cross section, its molecular formula, and its fragmentation pattern, properties that are central to understanding a molecule’s structure.

 

“Two different molecules can have the same number of atoms, and the same mass and charge, but they could have very different structures and activity. That’s where SLIM comes in to tell the difference,” said Hollerbach. “Just one small change can mean the difference between a molecule that is indicative of a disease and one that’s not.”

The key to Hollerbach’s experiment was getting the two different instruments to play nicely together. While both standard mass spectrometry and ion mobility spectrometry analyze ions, they work on different time scales. Ions make their journey through SLIM and arrive at the Orbitrap faster than they can be processed.

 

So Hollerbach drew on an old technique, deploying “dual-gated ion injection.” He added gates to control the intake of ions into the system and to control their arrival at the Orbitrap, choosing to send some of the ions from SLIM into oblivion to keep the flow at a manageable rate.

 

“Really, the questions we ask are very simple,” said Hollerbach. “What is this, and how much is there? But the techniques we use are complex.”

 

Other m/q scientists are working on additional ways to identify or exploit unknown molecules. Some are creating ways to use data like that from Hollerbach’s experiment to predict an ion’s structure automatically, so drug makers and other scientists would know exactly what they’re working with. Others are scouting out the millions of possibilities for forms of compounds such as fentanyl, sorting out what’s unlikely from what might show up on the street one day. Then they predict how those compounds would behave inside a mass spectrometer—creating a way to identify them if and when they do show up.

 

The work described in the Analytical Chemistry paper was funded by the m/q Initiative at PNNL. The mass spectrometry measurements were made at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at PNNL.

 

In addition to Hollerbach and Metz, PNNL authors of the paper are Yehia M. Ibrahim, Vanessa Meras, Randolph V. Norheim, Adam P. Huntley, Robert G. Ewing, and Richard D. Smith. Gordon Anderson, formerly of PNNL, with GAA Custom Engineering LLC in Benton City also contributed.

 

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About PNNL

Pacific Northwest National Laboratory draws on its distinguishing strengths in chemistry, Earth sciences, biology and data science to advance scientific knowledge and address challenges in sustainable energy and national security. Founded in 1965, PNNL is operated by Battelle for the Department of Energy’s Office of Science, which is the single largest supporter of basic research in the physical sciences in the United States. DOE’s Office of Science is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science. For more information on PNNL, visit PNNL's News Center. Follow us on Twitter, Facebook, LinkedIn and Instagram.

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JOURNAL

Analytical Chemistry

DOI

10.1021/acs.analchem.3c00881 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

A Dual-Gated Structures for Lossless Ion Manipulations-Ion Mobility Orbitrap Mass Spectrometry Platform for Combined Ultra-HighResolution Molecular Analysis

New model provides unprecedented window into human embryonic development

Peer-Reviewed Publication

YALE UNIVERSITY

Two to three weeks after conception, an embryo faces a critical point in its development. In the stage known as gastrulation, the transformation of embryonic cells into specialized cells begins. This initiates an explosion of cellular diversity in which the embryonic cells later become the precursors of future blood, tissue, muscle, and more types of cells, and the primitive body axes start to form. Studying this process in the human-specific context has posed significant challenges to biologists, but new research offers an unprecedented window into this point in time in human development.

 

A recent strategy to combat these challenges is to model embryo development using stem cell technologies, with many valuable approaches emerging from research groups across the globe. But embryos don’t grow in isolation and most previous developmental models have lacked crucial supporting tissues for embryonic growth. A groundbreaking model that includes both embryonic and extraembryonic components will allow researchers to study how these two parts interact around gastrulation stages—providing a unique look at the molecular and cellular processes that occur, and offering potential new insights into why pregnancies can fail as well as the origins of congenital disorders. The team, including Berna Sozen, PhD, and Zachary Smith, PhD, both assistant professors of genetics at Yale School of Medicine (YSM), published its findings in Nature on [tk].

 

“This work is extremely important as it provides an ethical approach to understand the earliest stages of human growth,” says Valentina Greco, PhD, the Carolyn Walch Slayman Professor of Genetics at YSM and incoming president-elect of the International Society for Stem Cell Research (ISSCR), who was not involved in the study. “This stem cell model provides an excellent alternative to start to understand aspects of our own early development that is normally hidden within the mother’s body.”

 

“The Sozen and Smith groups have achieved a milestone in developing in vitro models to study the earliest stages of human development that are unfeasible yet so important for understanding health and disease,” says Haifan Lin, PhD, the Eugene Higgins Professor of Cell Biology, director of the Yale Stem Cell Center, and president of ISSCR. “I commend their exceptional accomplishment as well as their sensitivity to ethical issues by limiting the model’s ability to develop further”

 

The ethical questions are profound, including whether these models have the potential to develop into human beings. Sozen, the principal investigator of the study, emphasizes that they do not. The published paper demonstrates that this model lacks trophectodermal cells, which are required for an embryo to implant in the uterus. Sozen says this model also represents a developmental stage beyond the time frame in which embryos can implant. “It is very important to focus on the fact that our model cannot grow further or implant and therefore is not considered a human embryo,” she says. But as a reductionist strategy to mimic and study aspects of natural development, its potential is immense, especially where universal guidelines severely limit scientists’ ability to study actual embryos.

 

New Model Contains Embryonic and Extraembryonic Tissues

 

All embryos have two components—embryonic and extraembryonic. The tissues we have now in our adult bodies grew from the embryonic component. The extraembryonic component includes the tissues that offer nutritional and other support, such as the placenta and yolk sac. The majority of previous embryo models of developmental stages around gastrulation were single-tissue models that only contained the embryonic component.

 

In the new study, the Yale-led team grew embryonic stem cells in vitro in the lab to generate their new model. They transferred these cells into a 3D culture system and exposed them to a conditions which stimulated the cells to spontaneously self-organize and differentiate. The cells diverged into two lineages—embryonic and extraembryonic precursors. The extraembryonic cells in this model were precursors for the yolk sac. The researchers grew these cellular lineages in the culture for approximately one week and analyzed how they guided each other as they developed. “We started looking into very mechanistic details, such as what signals they are giving each other and how specific genes are impacting one another,” says Sozen. “This has been limited in the literature previously.”

 

The Need for Models of Human Development

 

While researchers have learned a great deal from embryos of other species such as mouse, the lack of accessibility to human embryos has left significant knowledge gaps about our development. “If you want to understand human development, you need to look at the human system,” says Sozen. “This work is really important because it’s giving us direct information about our own species.” Not only does this model give access into the human gastrulation window, but will also allow for a greater quantity of research. The ability to generate as many as thousands of these models will allow for mass analysis that is not possible with human embryos. “I’m one scientist with one vision,” says Sozen. “But thinking about what other scientists are envisioning globally and what we can all accomplish is just really, really exciting to me.”

 

The new model has over 70% efficiency—in other words, the stem cells aggregate correctly over roughly 70% of the time. As noted by the authors, there are some limitations to the strategy, and it is challenging to benchmark some findings against the natural embryo itself. Sozen hopes to continue to work on the models so that they become more standardized in the future.

 

The team believes the models will transform scientists’ knowledge around human developmental biology. In their latest publication, the team explored some of the molecular paths underlying human gastrulation onset. In future studies, they hope to delve even deeper into the developmental pathways, including whether pregnancy loss and congenital disorders may stem from failures during gastrulation stages. Sozen believes her model can be used to look at some of these disorders and learn more about what is going awry. “Previous model systems have been able to look at this, but our model is unique because it has this extra tissue that allows us to analyze a bit deeper,” she says.  

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JOURNAL

Nature

DOI

10.1038/s41586-023-06354-4 

ARTICLE TITLE

Self-patterning of human stem cells into post-implantation lineages

ARTICLE PUBLICATION DATE

27-Jun-2023

UC Irvine scientists develop freely available risk model for hurricanes, tropical cyclones

The model could help countries around the world estimate storm impacts and costs

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - IRVINE

Irvine, Calif., June 27, 2023 — As human-driven climate change amplifies natural disasters, hurricanes and typhoons stand to increase in intensity. Until now, there existed very few freely available computer models designed to estimate the economic costs of such events, but a team of researchers led by Jane W. Baldwin at the University of California, Irvine recently announced the completion of an open-source model that stands to help countries with high tropical cyclone risks better calculate just how much those storms will impact their people and their economies.

“Tropical cyclones are some of the most impactful natural disasters on Earth. They pose huge risks to both human life and the built environment, so they have large economic costs associated with them and cause a lot of deaths,” said Baldwin, a professor in the UCI Department of Earth System Science and the lead author of the new paper in the American Meteorological Society journal Weather, Climate, and Society. “We need to be able to quantitatively explain their risk, meaning the probability of seeing different levels of losses.”

The economic risk model the team built extends an existing global tropical cyclone model, called the “Columbia tropical cyclone hazard” model. The economic risk model is prototyped for the Philippines but is straightforwardly customizable to any part of the world where stakeholders want to understand the storm risks they face.

Storms are called hurricanes when they form over the North Atlantic, typhoons when they form over the Northwest Pacific, and tropical cyclones when they form over in the Indian Ocean or South Pacific. 

The benefit of the new model is that countries that may not be able to afford access to other such risk models and associated vulnerability data, which typically belong to for-profit insurance companies that do not freely share their products or data, can get a clearer picture of the risks they face.

“That’s a strong motivation of the work, to expand the accessibility of tropical cyclone risk information,” said Baldwin.

It’s one reason why the country the team used as a case study in their research was the Philippines. That country, according to the researchers, faces among the highest number of landfalling tropical cyclones on Earth in any given year, but it is relatively less equipped when it comes to gauging the losses it may incur as a result.

The new model is unique in that it combines data from two disparate fields: climate change science from experts like Baldwin, and household vulnerability information acquired from data from the World Bank.

“Connecting these data is useful for people-focused disaster preparedness and response,” said Brian Walsh, an economist with the World Bank and an author on the new study. “That means rapid assistance to needful households, so that families can meet basic needs, children can return to schools, and communities can build back better.”

“What the model gives is return periods of asset losses, so that means total dollars lost from storms across different regions in the Philippines at different probabilities, at different levels of rarity,” said Baldwin. “There’s a pretty strong understanding that the strongest tropical cyclones should become more intense going into the future. But there’s still a lot of disagreement about how you go from that understanding to estimates of risk on the ground that are usable and help people constrain their adaptation needs.”

Beyond forecasting the monetary costs, the model can also help countries and even certain large municipalities to better prepare for a tropical cyclone by allowing them to understand exactly where they should spend time and resources preparing for such disasters. 

“There’s a growing need to be able to merge information from academic fields like climate science and these more applied risk modeling enterprises,” said Baldwin. “It’s a burgeoning field that I’m hoping will continue to develop over the next few years of catastrophe modeling as an academic enterprise and not just as a private enterprise. And I think climate change is really pushing the need for that dialogue.”

Joining Baldwin for this project were researchers from Lamont-Doherty Earth Observatory in Palisades, New York; the World Bank in Washington, D.C.; and Columbia University in New York.

About the University of California, Irvine: Founded in 1965, UCI is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation, and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224-degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UCI, visit www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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JOURNAL

Weather Climate and Society

ARTICLE TITLE

Vulnerability in a Tropical Cyclone Risk Model: Philippines Case Study

ARTICLE PUBLICATION DATE

27-Jun-2023

DNA barcoding identifies the plants a person has eaten

Reliable technique should improve clinical trials, nutrition studies and historical research

Peer-Reviewed Publication

DUKE UNIVERSITY

 

IMAGE: DNA BARCODING CAN NOW BE USED TO IDENTIFY WHAT PLANTS A PERSON HAS EATEN, AND IN WHAT RELATIVE AMOUNTS. THE TECHNIQUE SHOULD IMPROVE CLINICAL TRIALS AND NUTRITION STUDIES. (IMAGE, LAWRENCE A. DAVID) view more 

CREDIT: LAWRENCE A. DAVID, DUKE UNIVERSITY

DURHAM, N.C. – 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 trnL from 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).

CITATION: “Diversity of Plant DNA in Stool is Linked to Dietary Quality, Age and Household Income,” Brianna L. Petrone, Ammara Aqeel, Sharon Jiang, Heather K. Durand, Eric P. Dallow, Jessica R. McCann, Holly K. Dressman, Zhengzheng Hu, Christine B. Tenekjian, William S. Yancy, Jr., Pao-Hwa Lin, Julia J. Scialla, Patrick C. Seed, John F. Rawls, Sarah C. Armstrong, June Stevens, Lawrence A. David. PNAS, June 27, 2023.

DOI: 10.1073/pnas.2304441120

Online: https://www.pnas.org/cgi/doi/10.1073/pnas.2304441120

DNA Barcoding can now be used to identify what plants a person has eaten, and in what relative amounts. The technique should improve clinical trials and nutrition studies. (Image, Lawrence A. David)

CAPTION

DNA Barcoding can now be used to identify what plants a person has eaten, and in what relative amounts. The technique should improve clinical trials and nutrition studies. (Image, Lawrence A. David)

CREDIT

Lawrence A. David, Duke University

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2304441120 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Diversity of Plant DNA in Stool is Linked to Dietary Quality, Age and Household Income

ARTICLE PUBLICATION DATE

27-Jun-2023

Illinois study reveals genetic secrets of America's favorite snack

Peer-Reviewed Publication

UNIVERSITY OF ILLINOIS COLLEGE OF AGRICULTURAL, CONSUMER AND ENVIRONMENTAL SCIENCES

 

IMAGE: MULTIPLE TYPES OF POPCORN ILLUSTRATE SOME OF THE GENOMIC DIVERSITY FOUND IN A UNIVERSITY OF ILLINOIS STUDY. THE RESULTS COULD FACILITATE FUTURE BREEDING EFFORTS TO CREATE YUMMIER AND EASIER-TO-GROW VERSIONS OF AMERICA'S FAVORITE SNACK. view more 

CREDIT: MADSEN SULLIVAN, UNIVERSITY OF ILLINOIS

URBANA, Ill. – In its simplest form, popcorn is pretty uncomplicated. Most supermarket varieties offer the choice of two kernel colors, yellow or white, and two kernel shapes, pointed or pearl. When popped, the flake typically expands into one of two shapes: mushroom or butterfly. But there’s more to popcorn than meets the eye. New research from the University of Illinois Urbana-Champaign reveals a wealth of untapped diversity lurking in popcorn’s genetic code.

Analyzing 320 publicly available popcorn lines, crop sciences researchers found variation at more than 308,000 locations across the genome. This diversity may or may not translate into more popcorn variety for consumers, but some of the differences could be important for improving the agronomic performance of the crop.

“This could be helpful if popcorn companies wanted to bring in material to diversify their germplasm, which is super important for things like disease resistance and herbicide tolerance. More work has to be done to identify traits of interest, but this dataset opens up those possibilities,” says study co-author Tony Studer, associate professor and popcorn breeder in the Department of Crop Sciences, part of the College of Agricultural, Consumer and Environmental Sciences at Illinois.

Studer’s team documented the genetic differences in a process known as genotyping by sequencing, which narrows the focus of genetic sequencing efforts to the most information-packed parts of the genome. Differences, or polymorphisms, among corn lines occurred at the level of single nucleotides, the building blocks of DNA.

Popcorn populations

Having identified hundreds of thousands of differences, the team could then group corn lines by patterns of single nucleotide polymorphisms (SNPs), allowing the researchers to make inferences about relatedness. According to the analysis, North American popcorns fall into two groups: One primarily composed of yellow pearl types, with white pointed and Latin American types falling into a second group.

“Grouping popcorn based on genetic similarities allows us to look at the diversity present in each group and better predict the performance of crosses between lines. In addition, if a gene is found to improve performance, knowing its group membership will help breeders incorporate it into their program, something I hope popcorn companies will take advantage of to improve their products both on the consumer side and the grower side,” says Madsen Sullivan, doctoral student in crop sciences and the study’s first author.

The results showed a high level of inbreeding among yellow pearl popcorns. That means lower genetic diversity and greater relatedness among that group. Although this has resulted in better popping traits, material from the other group will likely contain versions of genes that could be useful but are not present in the yellow pearl popcorns.

The analysis also provides a starting point from which to uncover popcorn’s long history of movement across North America and the world. Studer says the first people to consume corn likely ate it popped, not buttered on the cob. He’s working to trace popcorn’s early origins in a follow-up study.

Demystifying popcorn’s herbicide tolerance

With popcorn’s genetic code spelled out, the researchers were eager to tackle a longstanding mystery related to herbicide application labels. Nicosulfuron has been killing weeds in cornfields since the early 1990s, but it’s only labeled for yellow-kerneled hybrids; farmers are specifically warned against using it on white-kerneled popcorn.  

“That was a red flag to me, because kernel color should have nothing to do with herbicide sensitivity,” says co-author Marty Williams, USDA-ARS ecologist and affiliate professor of crop sciences at Illinois. “Kernel color is controlled by genes in a completely different part of the genome.”

Williams worked with Studer’s team to test 294 popcorn genotypes from both populations, the yellow pearl group and the white pointed and Latin American group; incidentally, neither group is exclusively yellow or white, despite their names. The researchers applied nicosulfuron to the test group as well as sensitive and tolerant popcorn and sweet corn hybrids as controls.

While nicosulfuron did injure more white-kerneled popcorns, the effect had nothing to do with kernel color itself. Instead, nicosulfuron sensitivity correlated with genetic heritage and population structure. The pointed and Latin American types were more sensitive than yellow pearls. In dent corn, nicosulfuron is detoxified by a gene known as nsf1. The researchers immediately looked for the same gene in popcorn, assuming it would be active in the tolerant genotypes.

“We expected nsf1 to come up in popcorn, but instead we found a whole different set of genes that seemed to relate to nicosulfuron tolerance,” Studer says. “That opens up the possibility of an alternate mechanism for herbicide tolerance in popcorn, and we’re planning to follow up on that.”

Next steps

Williams recommends popcorn breeders use this research to improve tolerance to nicosulfuron, and perhaps other herbicides, in their existing and new cultivars.  Then herbicide labels ultimately could be updated to reflect tolerance throughout the crop, regardless of kernel color.

Could the results of the genome study improve popcorn’s agronomic traits? Studer says it will take more work to screen the dataset for desirable traits, but eventually elite popcorn lines could be developed and marketed by popcorn companies.

The study, “Genetic diversity of North American popcorn germplasm and the effect of population structure on nicosulfuron response,” is published in Crop Science [DOI: 10.1002/csc2.21039]. Madsen Sullivan, Marty Williams, and Tony Studer are authors. The research received funding from the University of Illinois, and Sullivan was supported by a fellowship from the Illinois Corn Growers Association.

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JOURNAL

Crop Science

ARTICLE TITLE

Genetic diversity of North American popcorn germplasm and the effect of population structure on nicosulfuron response

 DICKENSIAN PHOBIA

Bias in health care: study highlights discrimination toward children with disabilities

Peer-Reviewed Publication

UNIVERSITY OF UTAH HEALTH

Children with disabilities, and their families, may face discrimination in in the hospitals and clinics they visit for their health care, according to a new study led by researchers at University of Utah Health. These attitudes may lead to substandard medical treatment, which could contribute to poor health outcomes, say the study’s authors.

“They mistreated her and treated her like a robot. Every single time a nurse walked in the room, they treated her like she was not even there,” said one mother who was interviewed about her child’s health care encounters.

The findings, published in the journal Pediatrics, are based on 30 in-depth interviews with family caregivers living in 15 states in the U.S. The children they looked after had medically complex conditions, with most needing health care more than 20 times each year. While the study did not measure how common it is for clinicians to show bias against children with disability, it exposes a serious problem that needs to be addressed, says lead author Stefanie Ames, M.D., a critical care physician at U of U Health.

“Our goal was to validate families’ experiences and bring awareness to the issue,” Ames says. She and the study’s senior author, Nancy Murphy, M.D., are faculty in the Department of Pediatrics at the Spencer Fox Eccles School of Medicine at the University of Utah. “Recognizing the problem is the first step.”

Causes and Consequences of Bias

Analysis of interviews with caregivers identified six recurring reasons for, and consequences of, health care provider bias against children with disability and complex medical conditions.

Family caregivers perceived that the main drivers of discrimination were:

• A lack of knowledge of how to care for children with complex medical needs
• A lack of interest in providing health care or medical interventions based on a perception that the child may not be worthy of care  
• Negative assumptions based on the child’s disability and quality of life

The interviews revealed that family caregivers felt that discrimination resulted in:

• Limited accommodations, for example for wheelchairs, making it difficult for children and their families to access health care
• Clinicians not providing the same health care and medical treatments to children with disabilities as they would for those without disabilities
• Clinicians dehumanizing children with disability and treating them differently than they would typically developing children 

According to family caregivers, these attitudes, at times, impacted patient care. One said that a doctor recommended against treating her daughter’s cancer despite there being a high chance of success that the treatment would work. Another parent indicated that health care providers did not give her child adequate pain relievers before carrying out an uncomfortable medical procedure.

“My perception is that [clinicians] wanted to take care of the patients that didn’t have a severe, special need… They just seemed like they didn’t even care to treat [my daughter],” said one child’s mother.

Ames and Murphy say the experiences of these families reveal an urgent need for additional medical training in caring for people with disability. The research team will be carrying out additional studies to determine how common these attitudes are nationally and whether they ultimately impact the health of children with complex medical needs.

“I believe that all healthcare providers choose this line of work because of the common goal of helping those in need,” Murphy says. “Yet when providers lack the knowledge, experience or resources to render care, we tend to shy away from situations. This tends to happen without our awareness, and this research brings this issue into clear view.”

# # #

The project was supported by a grant from the University of Utah Health Equity Research Core in the Woman and Child Institute and the Children and Youth with Special Healthcare Needs National Research Network.

In addition to Ames and Murphy, the study’s co-authors are Rebecca Delaney, Claudia Delgado-Corcoran, Justin Alvey, and Melissa Watt from U of U Health and Amy Houtrow from University of Pittsburgh. The research published as “Perceived disability-based discrimination in healthcare for children with medical complexity.”

About University of Utah Health

University of Utah Health  provides leading-edge and compassionate care for a referral area that encompasses Idaho, Wyoming, Montana, and much of Nevada. A hub for health sciences research and education in the region, U of U Health has a $458 million research enterprise and trains the majority of Utah’s physicians, and more than 1,670 scientists and 1,460 health care providers at its Colleges of Health, Nursing, and Pharmacy and Schools of Dentistry and Medicine. With more than 20,000 employees, the system includes 12 community clinics and five hospitals. U of U Health is recognized nationally as a transformative health care system and provider of world-class care.

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JOURNAL

PEDIATRICS

DOI

10.1542/peds.2022-060975 

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Perceived Disability-Based Discrimination in Health Care for Children With Medical Complexity

ARTICLE PUBLICATION DATE

26-Jun-2023

Fear of being exploited is stagnating our progress in science

Peer-Reviewed Publication

THE POLISH ASSOCIATION OF SOCIAL PSYCHOLOGY

 

IMAGE: RESEARCHERS IN LABORATORY view more 

CREDIT: RHODA BAER / NATIONAL CANCER INSTITUTE

Science is a collaborative effort. What we know today would have never been, had it not been generations of scientists reusing and building on the work of their predecessors.

However, in modern times, academia has become increasingly competitive and indeed rather hostile to the individual researchers. This is especially true for early-career researchers yet to secure tenure and build a name in their fields. Nowadays, scholars are left to compete with each other for citations of their published work, awards and funding. 

So, understandably, many scientists have grown unwilling to cooperate and help their peers by sharing their work. They would “hide” their raw data, despite having taken years-long efforts to collect. They would also conceal experiments that have failed or proved insignificant. All these practices would then result in different teams wasting precious time in running the same useless studies, rather than making further progress and contributing to the world’s knowledge.

In the meantime, recent years have witnessed a growing global push for open science: a movement standing for and celebrating an extensive set of good practices founded on transparency, collaboration and sharing.

This is why a German team of social psychologists from the LMU Munich and the University of Marburg ran a series of studies with scientists from across Europe and North America, in order to find what is driving researchers to withhold knowledge from their colleagues. Their results were recently published in the open-access peer-reviewed scholarly journal Social Psychological Bulletin.

“Knowledge hiding is problematic, not only for the private economy, but also in academia. One might say that knowledge hiding in the scientific domain is even more problematic because science should be all about acquiring, scrutinising, and disseminating knowledge,”

explain the authors of the study.

“If scientists were inclined to hide what they know from their peers, then accumulating scientific knowledge would be impossible and instead of maximising the collective effort of discovering the truth, science would merely produce unconnected, insular, and probably non-replicable single effects.”

According to their findings, a specific personality trait called “victim sensitivity” predicted knowledge hiding in science. Researchers with this personality trait are characterised by a latent fear of being exploited by others and, thus, are more suspicious about their colleagues.

The research team also tested whether reminding the participants about their identity as a “researcher” might help or hinder collaboration. Their motivation to observe the impact of this approach is linked to prior studies, which showed that people are inclined to favour those belonging to their own group.

Surprisingly, though, when participants in one of the studies got their sense of identity as “researchers” activated, they actually became more suspicious and ready to hide their knowledge. One explanation for this would be that being reminded of being a “researcher” activated an obstructive self-stereotype: a researcher is a highly ambitious person, but is cold, rather than caring and cooperative.

The good news, point out the authors of the study, is that - among the participants - the intention to hide knowledge was rather low.

However, the authors warn about a potential bias. It is likely that researchers who volunteered to take part in these studies were more cooperative to begin with. Additionally, it might be that in the context of self-reporting, the participants tried to present themselves as more likeable.

“We may need to change the stereotypical way we think about ourselves as researchers, in order to build trust and create a sharing environment among scientists,"

concludes the research team. 

“Identifying as a researcher should include being cooperative, other-oriented, and trustworthy: a social identity that stands for knowledge sharing – not knowledge hiding.”

Research article:

Altenmüller, M. S., Fligge, M., & Gollwitzer, M. (2023). Among Us: Fear of Exploitation, Suspiciousness, and Social Identity Predict Knowledge Hiding Among Researchers. Social Psychological Bulletin, 18, 1-22. https://doi.org/10.32872/spb.10011

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JOURNAL

Social Psychological Bulletin

DOI

10.32872/spb.10011 

ARTICLE TITLE

Among Us: Fear of Exploitation, Suspiciousness, and Social Identity Predict Knowledge Hiding Among Researchers