Insights & Outcomes: Extra electrons, virtual scribes, and a streaming service for bacteria
This month, Insights & Outcomes binges out on the behavior of bacteria, leans into the latest chemical reductants, and shines a light on government requirements for clinical trial data. Plus, we check up on the value of virtual scribes and salute a pair of faculty award winners.
More electrons, please
When your goal is to create new chemical products or pharmaceuticals, there are times when an electron source — in the form of a chemical compound known as a reductant — can be your best friend.
For example, reductants are used to neutralize contaminants in wastewater and to prepare bleaching reagents on an industrial scale.
A team of Yale chemists led by Nilay Hazari, working with researchers at the pharmaceutical firm Merck & Co., have developed a versatile new group of reductants that may prove useful in the discovery and preparation of pharmaceuticals. A study describing the soon-to-be commercially available reductants appears in the Journal of the American Chemical Society.
Importantly for practical applications, the new reductants can be used in the same phase of a chemical reaction as the substrates — the chemicals that are transformed into more valuable materials during the reaction — and the catalysts that initiate the reaction, making the reductants more versatile.
The reagents are also “tunable,” meaning their reactivity can be adjusted to match the substrate and catalyst.
“We have used this property to develop new reactions that are not possible with conventional reductants,” said Hazari, co-corresponding author of the study. “It is expected that these new reagents will make current reactions more practical and lead to the development of new reactions.”
Yale contributors to the study were co-first authors David Charboneau and Haotian “John” Huang, and co-authors Emily Barth, Cameron Germe, and Brandon Mercado.
How organisms process sensory information and translate the data they collect into behavior is complicated — even for bacteria like E. coli, which goes through life pursuing chemical attractants in its environment. Scientists at Yale analyzed this simple process, known as chemotaxis, to help answer a fundamental question: How efficiently do organisms use information to guide their behavior?
The answer, they found, is akin to using a streaming service such as Netflix.
Just as a device receives video data over an internet connection, E. coli gathers information about chemical attractants in its environment. The researchers first showed that, like a viewer seeking better video quality, the maximum speed E. coli could move up an attractant gradient is limited by its information bandwidth. But high bandwidth is not enough. The organism — or television, or computer — has to appropriately use the information it receives. “If the TV is garbage, the video quality is still poor no matter what the bandwidth is,” said co-lead author Henry Mattingly, postdoctoral researcher in the lab of co-senior author Thierry Emonet, professor of molecular, cellular, and developmental biology (MCDB), and of physics.
Scientists have long hypothesized that evolution has maximized the information processing capabilities of organisms to aid in their survival. The Yale team devised a way to test that hypothesis in the context of behavior by measuring E. coli cells’ information bandwidths and how fast they move in response to chemical cues. To estimate bandwidth, the team used a fluorescent reporter system to measure the activity of a molecular sensor inside of individual E. coli cells that is crucial to their ability to track environmental chemicals. They found that, despite the bacterium’s tiny bandwidth — millions of times smaller than a typical internet connection — E. coli use their information efficiently, traversing gradients at close to the theoretical maximum speed.
“This example is simple, but the finding is a stepping stone to understanding how information can shape behavior in more complex organisms,” Mattingly said.
Keita Kamino, associate research scientist in MCDB and Benjamin Machta, assistant professor of physics, are co-lead and co-senior authors of the study, which was published in the journal Nature Physics.
Electronic health records (EHRs) are meant to improve efficiency in health care, but their use has been associated with physician burnout. In a recent study in the New England Journal of Medicine Catalyst, Yale researchers explored one way that hospitals might manage EHR burden — offering a helping hand.
The research team evaluated how the use of virtual scribes — real people who tune into patient visits via microphone and speaker and jot down meeting notes — affected physicians’ EHR experiences. These scribes assisted the physicians with visit documentation and other EHR-related tasks. Most of the physicians observed — over 80% — spent less time writing notes and less time using EHRs once they began working with scribes. And their note quality improved as well.
To better understand why some physicians appeared to benefit from working with scribes and some did not, the researchers compared the two groups’ EHR activity before they began working with scribes. As it turns out, the physicians who responded well to scribes’ help were spending more time writing notes and using EHRs than were their counterparts.
“So not only do scribes really help some physicians,” said Shawn Ong, an assistant clinical professor in the Department of Internal Medicine, “we can also use physicians’ EHR activity to pinpoint who might benefit most from working with them.”
A clean sweep for Martha Muñoz
Martha Muñoz has spent much of her research career watching lizards.
Sitting on logs with a pair of binoculars, she observed that lizards in Costa Rica, perhaps wary of predators, tend to be sedentary, moving about their habitats quite rarely. However, the same types of lizards in the Caribbean are much nimbler, constantly on the move between patches of shade and sunlight. These observations eventually led Muñoz to a startling conclusion — the behavior of animals helped shaped their own evolutionary fate.
“These animals are not passive vessels at the whim of their environment. They are endowed with ability to build their own evolutionary capacities,” Muñoz said. In November, Muñoz, assistant professor of ecology and evolutionary biology at Yale, received the George A. Bartholomew Award from the Society for Integrative & Comparative Biology for her work in the field of comparative physiology. She also received the 2021 Carl Gans Award, becoming the first to sweep the society’s top two awards.
Muñoz’ work showed that behaviors function as vital “pacemakers” for evolution. When organisms — like the Caribbean and Central American anoles she studied — use behavioral strategies to shield themselves from natural selection, their physiological evolution is surprisingly sluggish. By contrast, when lizards are less behaviorally active, they are exposed to greater selection and their physiology evolves much more rapidly. In essence, the day-to-day behaviors of organisms create ripples across millions of years of evolution. “The lizards are both targets and agents of evolution,” she said.
Showing the Love for Bercovici
The European Geosciences Union (EGU) is showing some Love for Yale’s David Bercovici, the Frederick William Beinecke Professor of Earth & Planetary Sciences in the Faculty of Arts and Sciences.
EGU has awarded Bercovici the 2022 Augustus Love Medal, given to a distinguished scientist in the field of geodynamics, comprising mantle and core convection, tectonophysics, post-glacial rebound, and Earth rotation. Previous winners include Yale’s Shun-Ichiro Karato.
Bercovici, a member of the Yale faculty since 2001, has produced field-leading research on a wide range of topics, including carbon sequestration, the origin of plate tectonics, volcanic flows and eruptions, mantle convection, and lithosphere dynamics. Bercovici is co-director of the Yale Center for Natural Carbon Capture, which is part of the Yale Planetary Solutions Project.
The Love medal, named for the influential British scientist Augustus Love, will be celebrated during the EGU General Assembly 2022, April 3-8 in Vienna, Austria.
Trial and error
By law, clinical trial sponsors must submit their trial results to ClinicalTrials.gov — a publicly accessible website that aims to promote transparency in clinical trial research. But in thousands of trials, these sponsors do not report their results on time.
The U.S. Food and Drug Administration (FDA) can enforce the law but has only recently begun to publicly exert its power, issuing its first Notice of Noncompliance to a pharmaceutical company in April 2021.
The Notice of Noncompliance is the second step in the FDA’s process, coming after a Preliminary Notice of Noncompliance that serves as a warning. To get a better understanding of the FDA’s actions to date, Yale researchers filed a Freedom of Information Act request for the preliminary notices served by the agency as of April 2021.
The FDA issued just 58 preliminary notices and, in a new article in the Journal of the American Medical Association, the researchers found they were actually pretty useful, albeit few in number.
“As of mid-August, more than 90% of the preliminary notice recipients had reported their missing information to ClinicalTrials.gov,” said Reshma Ramachandran, a National Clinician Scholars Program Fellow at the Yale School of Medicine. “And most did so fairly soon after receiving the notice.”
The researchers noted that with thousands of incomplete clinical trial records, the FDA should strengthen its efforts by sending more preliminary notices, publicizing them, and laying out enforcement timelines within them.
Staff writers Jim Shelton, Bill Hathaway, and Mallory Locklear contributed to this column.