New materials could enable longer-lasting implantable batteries

Pacemakers and other medical devices, as well as long-distance drones and remote sensors, could require fewer battery replacements with new approach.

Peer-Reviewed Publication

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

 

IMAGE: TIME-LAPSE SERIES OF IMAGES SHOWS THE NEW TYPE OF BATTERY BECOMING FULLY DISCHARGED OVER A PERIOD OF DAYS. IN THE PROCESS OF DISCHARGING, THE NEW "CATHOLYTE" MATERIAL IN THE BATTERY CELL GETS CHEMICALLY COVERTED INTO A REDDISH COMPOUND, SO THE COLOR GETS DARKER THE MORE IT DISCHARGES. view more 

CREDIT: IMAGE COURTESY OF HAINING GAO, ALEJANDRO SEVILLA, AND BETAR GALLANT, ET. AL

For the last few decades, battery research has largely focused on rechargeable lithium-ion batteries, which are used in everything from electric cars to portable electronics and have improved dramatically in terms of affordability and capacity. But nonrechargeable batteries have seen little improvement during that time, despite their crucial role in many important uses such as implantable medical devices like pacemakers.

 

Now, researchers at MIT have come up with a way to improve the energy density of these nonrechargeable, or “primary,” batteries. They say it could enable up to a 50 percent increase in useful lifetime, or a corresponding decrease in size and weight for a given amount of power or energy capacity, while also improving safety, with little or no increase in cost.

 

The new findings, which involve substituting the conventionally inactive battery electrolyte with a material that is active for energy delivery, are reported today in the journal Proceedings of the National Academy of Sciences, in a paper by MIT Kavanaugh Postdoctoral Fellow Haining Gao, graduate student Alejandro Sevilla, associate professor of mechanical engineering Betar Gallant, and four others at MIT and Caltech.

 

Replacing the battery in a pacemaker or other medical implant requires a surgical procedure, so any increase in the longevity of their batteries could have a significant impact on the patient’s quality of life, Gallant says. Primary batteries are used for such essential applications because they can provide about three times as much energy for a given size and weight as rechargeable batteries.

 

That difference in capacity, Gao says, makes primary batteries “critical for applications where charging is not possible or is impractical.” The new materials work at human body temperature, so would be suitable for medical implants. In addition to implantable devices, with further development to make the batteries operate efficiently at cooler temperatures, applications could also include sensors in tracking devices for shipments, for example to ensure that temperature and humidity requirements for food or drug shipments are properly maintained throughout the shipping process. Or, they might be used in remotely operated aerial or underwater vehicles that need to remain ready for deployment over long periods.

 

Pacemaker batteries typically last from five to 10 years, and even less if they require high-voltage functions such as defibrillation. Yet for such batteries, Gao says, the technology is considered mature, and “there haven’t been any major innovations in fundamental cell chemistries in the past 40 years.”

 

The key to the team’s innovation is a new kind of electrolyte — the material that lies between the two electrical poles of the battery, the cathode and the anode, and allows charge carriers to pass through from one side to the other. Using a new liquid fluorinated compound, the team found that they could combine some of the functions of the cathode and the electrolyte in one compound, called a catholyte. This allows for saving much of the weight of typical primary batteries, Gao says.

 

While there are other materials besides this new compound that could theoretically function in a similar catholyte role in a high-capacity battery, Gallant explains, those materials have lower inherent voltages that do not match those of the remainder of the material in a conventional pacemaker battery, a type known as CFx. Because the overall output from the battery can’t be more than that of the lesser of the two electrode materials,  the extra capacity would go to waste because of the voltage mismatch. But with the new material, “one of the key merits of our fluorinated liquids is that their voltage aligns very well with that of CFx,” Gallant says.

 

In a conventional  CFx battery, the liquid electrolyte is essential because it allows charged particles to pass through from one electrode to the other. But “those electrolytes are actually chemically inactive, so they’re basically dead weight,” Gao says. This means about 50 percent of the battery’s key components, mainly the electrolyte, is inactive material. But in the new design with the fluorinated catholyte material, the amount of dead weight can be reduced to about 20 percent, she says.

 

The new cells also provide safety improvements over other kinds of proposed chemistries that would use toxic and corrosive catholyte materials, which their formula does not, Gallant says. And preliminary tests have demonstrated a stable shelf life over more than a year, an important characteristic for primary batteries, she says.

 

 

So far, the team has not yet experimentally achieved the full 50 percent improvement in energy density predicted by their analysis. They have demonstrated a 20 percent improvement, which in itself would be an important gain for some applications, Gallant says. The design of the cell itself has not yet been fully optimized, but the researchers can project the cell performance based on the performance of the active material itself. “We can see the projected cell-level performance when it’s scaled up can reach around 50 percent higher than the CFx cell,” she says. Achieving that level experimentally is the team’s next goal.

 

Sevilla, a doctoral student in the mechanical engineering department, will be focusing on that work in the coming year. “I was brought into this project to try to understand some of the limitations of why we haven’t been able to attain the full energy density possible,” he says. “My role has been trying to fill in the gaps in terms of understanding the underlying reaction.”
 

One big advantage of the new material, Gao says, is that it can easily be integrated into existing battery manufacturing processes, as a simple substitution of one material for another. Preliminary discussions with manufacturers confirm this potentially easy substitution, Gao says. The basic starting material, used for other purposes, has already been scaled up for production, she says, and its price is comparable to that of the materials currently used in CFx batteries. The cost of batteries using the new material is likely to be comparable to the existing batteries as well, she says. The team has already applied for a patent on the catholyte, and they expect that the medical applications are likely to be the first to be commercialized, perhaps with a full-scale prototype ready for testing in real devices within about a year.

 

Further down the road, other applications could likely take advantage of the new materials as well, such as smart water or gas meters that can be read out remotely, or devices like EZPass transponders, increasing their usable lifetime, the researchers say. Power for drone aircraft or undersea vehicles would require higher power and so may take longer to be developed. Other uses could include batteries for equipment used at remote sites, such as drilling rigs for oil and gas, including devices sent down into the wells to monitor conditions.

 

The team also included Gustavo Hobold, Aaron Melemed, and Rui Guo at MIT and Simon Jones at Caltech. The work was supported by MIT Lincoln Laboratory and the Army Research Office.

###

Written by David L. Chandler, MIT News Office

Additional background

Paper: “Fluoro-Organosulfur Catholytes to Boost Lithium Primary Battery Energy”

https://www.pnas.org/doi/10.1073/pnas.2121440119

 

---

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.212144011 

ARTICLE TITLE

“Fluoro-Organosulfur Catholytes to Boost Lithium Primary Battery Energy”

New center empowers climate storytellers across the communications landscape

Business Announcement

UNIVERSITY OF SOUTHERN CALIFORNIA

 

IMAGE: PHOTO BY LI-AN LIM ON UNSPLASH view more 

CREDIT: LI-AN LIM

As world leaders prepare to meet this month at the United Nations Climate Change Conference in Egypt, journalists and communications professionals around the globe are gearing up to cover the negotiations. And a new center at the USC Annenberg School is ready to improve the impact of climate communication.

The school has launched the Center for Climate Journalism and Communication that empowers professionals across media, public relations, and strategic and corporate communications to be climate storytellers who advance a deeper understanding of the consequences of climate change — from the global to the local and from the collective to the individual. The center provides critical training to understand climate science, to capture its effects, particularly when felt disproportionately in under-resourced communities, and to support action that preserves the health of the planet and its inhabitants.

“The climate crisis is one of the most significant stories of our lifetime and we must do a better job telling it,” USC Annenberg Dean Willow Bay said. “The center emboldens professional journalists and communicators — with discipline specific training, support and mentoring — to tell this story as if our lives depend upon it.”

Leveraging USC’s academic scholarship, targeted research initiatives and professional training expertise, the center designs customized programs for news and communication organizations.

“From our neighbors who are experiencing climate change, to scientists and scholars who research the subject, we know that climate change is real and it’s happening now,” said Allison Agsten, the center’s inaugural director. “We have an imperative to train — and support — professional and aspiring journalists and communicators who can combine powerful narratives, data grounded in science, and engagement with communities they serve to drive systemic change.”

Developed in collaboration with long-standing USC Annenberg partner ABC Owned Television Stations, the center’s first climate training program for news organizations begins this month. Local TV news journalists in eight U.S. markets — ranging from assignment editors and executive producers to meteorologists and race and culture reporters — will learn from experts in big data processing, ethical image selection, decision science and climate resilience. Journalists will also produce a data report outlining climate impacts in their regions and stories that capture the ramifications on residents in their local communities.

“Now, more than ever, we need to train and support journalists to accurately report on the current and future climate crisis,” said Chad Matthews, president, ABC Owned Television Stations. “The center’s program is invaluable as our journalists strive to deliver the quality reporting our stations are known for, and to create climate journalism that is accessible, understandable, and actionable for the average consumer.”

In addition, the center helps practitioners in public relations, corporate communications and advocacy improve their own environmental storytelling capabilities. At a moment when awareness — and distrust — of environmental, social and governance (ESG) is expanding, the center has commissioned intelligence from Zignal Labs to gauge the challenges inherent in ESG reporting.

In September, the center kicked off its virtual “Covering Climate” series, which provides easily accessible programming for working journalists and students to explore topics and connect with leaders in climate reporting, research and activism.

For students, the center provides foundational training in climate communication both through publishing opportunities in USC Annenberg courses as well as the school’s student-led news organization Annenberg Media.

Recent projects developed by students in the COMM 499: Climate Stories course and through the journalism master’s summer immersion program have been published by outlets and websites such as Now This Earth, Surfrider Foundation, the NOAA’s Sea Grant, among others.

This Fall, Agsten collaborated with Annenberg Media to establish the Earth Desk, which will engage students of all majors to cover (and consume) climate-related news.

“By supporting the creation of the first Earth Desk, we are providing an opportunity for student journalists to learn how to incorporate climate into any story, on any beat, and in any field,” Agsten said.

Seed funding to support the center's formation came from Bloomberg Philanthropies along with Vere Initiatives and USC Annenberg parents, through the Beedie Foundation and the Manaaki Foundation.

“We are inspired by how the USC Annenberg community has come together to advance our collective climate story,” said Antha Williams, who leads Bloomberg Philanthropies’ Environment program. “We hope others will join us in helping to elevate and further this important work.”

---

METHOD OF RESEARCH

News article

Limiting antibiotics for cows may create a new dairy market

Peer-Reviewed Publication

CORNELL UNIVERSITY

ITHACA, N.Y. – Consumers would be willing to buy milk from cows only treated with antibiotics when medically necessary – as long as the price isn’t much higher than conventional milk, according to researchers at Cornell University.

The findings suggest conventional farmers could tap a potentially large market for this type of milk if they can find the right price point – and that dairy consumers can help slow the rise of antimicrobial resistance.

“Most of the antibiotics produced throughout the world are used for animal agriculture. Therefore, reducing antibiotic use in animals, including dairy cattle, is necessary to tackle antibiotic resistance at a global scale,” said Dr. Renata Ivanek, professor in the Department of Population Medicine and Diagnostic Sciences and senior author on the study, which published in the Journal of Dairy Science.

In the paper, the researchers propose a new label for milk that indicates responsible antibiotic use (RAU), which would leverage consumer preferences to reduce the use of antibiotics on commercial dairy farms. The study showed that, although a consumer’s willingness to pay for the RAU-labeled milk was comparable to how much they would pay for the unlabeled milk, they strongly preferred the RAU-labeled milk over the unlabeled milk option. Therefore, the researchers hypothesize this new RAU label would entice farmers to minimize antibiotics more than they do for conventional, unlabeled milk.

Too much antibiotic treatment in cows leads to the rise of resistant strains of bacteria, which can make antibiotics for both animals and humans less effective, the researchers note. “Consumers should know that their choices are important, and that their understanding of antibiotic use could move the dairy industry toward more sustainable milk production practices,” said Dr. Ece Bulut, research associate in the Department of Population Medicine and Diagnostic Sciences and co-author of the study.

The researchers conducted a nationally representative survey of U.S. adults, finding that half were willing to buy RAU-labeled milk. They also held a randomized, experimental auction with real money and milk, which showed that buyers were also willing to pay for RAU-labeled milk but only slightly more than they are willing to pay for the unlabeled cartons.

“What this means is that there could potentially be a large market for RAU milk as long as the price isn’t much higher than conventional milk, so it’s a possible new option for conventional farmers,” said Robert Schell, first author of the study.

A similar label for certified responsible antibiotic use (CRAU) is already used in the poultry industry, Bulut said. CRAU limits the use of medically important antibiotics – antibiotics used in human medicine – in poultry production. The researchers envision that the RAU label would similarly be determined by veterinarians and U.S. Department of Agriculture (USDA) standards, so that any carton of milk with an RAU label would come from a cow treated with antibiotics only when medically necessary.

“The existing literature suggests that larger bodies regulating these sorts of claims, like the USDA and CRAU certification, makes consumers more willing to trust and, as a result, buy products with desirable labels,” said Schell.

This study is an important initial step in exploring consumer attitudes toward an RAU label and its potential market for conventional farmers, the researchers said.

The work is the result of collaboration between the College of Veterinary Medicine, the Charles H. Dyson School of Applied Economics and Management, and the Department of Communication in the College of Agriculture and Life Sciences. The researchers also worked with Cornell’s Lab for Experimental Economics and Decision Research as well as Cornell’s Survey Research Institute.

Funding for this study was provided by the National Institute of Food and Agriculture, the USDA and the National Institutes of Health.

For additional information, see this Cornell Chronicle story.

-30-

---

JOURNAL

Journal of Dairy Science

DOI

10.3168/jds.2022-21791 

ARTICLE TITLE

Responsible antibiotic use labeling and consumers' willingness to buy and pay for fluid milk

Are covid ‘comas’ signs of a protective hibernation state?

Peer-Reviewed Publication

PICOWER INSTITUTE AT MIT

 

IMAGE: THE PAINTED TURTLE SHOWS SIMILAR SIGNS OF A PROTECTIVE DOWN STATE IN THE BRAIN. view more 

CREDIT: GARY ESLINGER/USFWS VIA HTTPS://EN.WIKIPEDIA.ORG/WIKI/PAINTED_TURTLE#/MEDIA/FILE:PAINTED_TURTLE_(14541060047).JPG

Many Covid-19 patients who have been treated for weeks or months with mechanical ventilation have been slow to regain consciousness even after being taken off sedation. A new article in the Proceedings of the National Academy of Sciences offers the hypothesis that this peculiar response could be the effect of a hibernation-like state invoked by the brain to protect cells from injury when oxygen is scarce.

A very similar kind of state, characterized by the same signature change of brain rhythms, is not only observed in cardiac arrest patients treated by chilling their body temperature, a method called “hypothermia,” but also by the painted turtle, which has evolved a form of self-sedation to contend with long periods of oxygen deprivation, or “anoxia,” when it overwinters underwater.

“We propose that hypoxia combined with certain therapeutic maneuvers may initiative an as yet unrecognized protective down-regulated state (PDS) in humans that results in prolonged recovery of consciousness in severe COVID-19 patients following cessation of mechanical ventilation and in post-cardiac arrest patients treated with hypothermia,” wrote authors Nicholas D. Schiff and Emery N. Brown. “In severe Covid-19 patients we postulate that the specific combination of intermittent hypoxia, severe metabolic stress and GABA-mediated sedation may provide a trigger for the PDS.”

Schiff is a Jerold B. Katz Professor of Neurology and Neuroscience in the Feil Family Brain Mind Research Institute at Weill Cornell Medicine. Brown is the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT. He is also an anesthesiologist at Massachusetts General Hospital and the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School.

A motivating observation for the pair’s hypothesis is that cardiac arrest patients treated with hypothermia, Covid-19 patients with prolonged wakeups after sedation and ventilation, and the hibernating painted turtle all exhibit a brain rhythm pattern called “burst suppression.” In the same journal a decade ago ShiNung Ching, Brown and co-authors described a model suggesting that burst suppression is an activity pattern signaling that the brain is reducing energy use when sufficient supplies are not available. In this way, the brain limits the damage that neurons could otherwise endure by trying to operate at full power.

 

“Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that preserves basic cellular function during states of lowered energy availability,” the authors wrote.

The turtles appear to achieve this state by rapidly ramping up the release of GABA, a neurotransmitter chemical known to reduce neural activity in the brain, hours after oxygen becomes scarce. This GABA release, known as the ‘endogenous anesthesia for the anoxic turtle brain’ reduces the energy demand of brain cells. The authors see a direct parallel in Covid patients who are often given sedatives whose effects are mediated by GABA.

Speeding recovery

If Brown and Schiff’s hypotheses are correct, they write, then there may be a principled two-part approach for better reviving Covid patients from unconsciousness after ventilation is removed.

The first part is to administer Szeto-Schiller peptides (small protein fragments) that are known to improve neurons production of the energy metabolism molecule ATP. This could restore the brain cells’ ability to produce energy when they return to a more active state.

The second part calls for a pair of drugs that will restore neural activity and communication by promoting the neurotransmitters glutamate and acetylcholine, essentially counteracting GABA’s tamping down of neural activity and metabolism.

“Our analysis predicts the existence of a human form of PDS that may underlie prolonged recovery of consciousness following treatment for severe Covid-19 or treatment for post-cardiac arrest treated with hypothermia,” Brown and Schiff wrote. “The possible existence of human PDS suggests many testable hypotheses for further investigation and the possibility of developing novel therapeutic strategies.”

---

JOURNAL

Proceedings of the National Academy of Sciences

METHOD OF RESEARCH

Literature review

SUBJECT OF RESEARCH

People

ARTICLE TITLE

"Protective down-regulated states in the human brain? An emerging lesson from COVID-19

ARTICLE PUBLICATION DATE

7-Nov-2022

The secret to the skillful skydiving of wingless springtails

Georgia Tech researchers discover how this tiny hexapod survives predators

Peer-Reviewed Publication

GEORGIA INSTITUTE OF TECHNOLOG

 

IMAGE: RESEARCHERS COLLECTING SPRINGTAILS view more 

CREDIT: GEORGIA TECH

Early in the pandemic, Víctor Ortega-Jiménez was exploring creeks near his home and observing springtails. The organisms are the most abundant non-insect hexapods on earth, and Ortega-Jiménez suspected their avoidance of predators had something to do with their ability to jump on the water surface and land perfectly in the same spot.  

Ortega-Jiménez brought the hypothesis back to his lab in Georgia Tech’s School of Chemical and Biomolecular Engineering (ChBE). Using a combination of computational and robophysical modeling, as well as fluid dynamics experiments, the researchers were able to see for the first time the mechanics of springtail movement. They determined how springtails control their jump, self-right in midair, and land on their feet — all within the blink of an eye — effectively saving them from predators.

“These extraordinary organisms with unique morphology live at a very precarious place: the water surface,” said ChBE Assistant Professor Saad Bhamla. “So, when they jump from and land back on water, we must understand the effects of both hydrodynamics and aerodynamics. How they land perfectly on their feet almost every time on the surface of water was the puzzle we set to solve in this paper.”

Ortega-Jiménez, Bhamla, and their collaborators presented this research in “Directional Takeoff, Aerial Righting, and Adhesion Landing of Semiaquatic Springtails,” published in the Proceedings of the National Academy of Sciences.

Springtails

CREDIT

Georgia Tech

Understanding Springtails

The researchers discovered that springtails are so successful because of posture and mostly by their unique appendages for jumping and adhesion. First, they adjust the angle of their leaping organ, the furcula, when they take off. Then they change their posture midair into a U-shape that creates aerodynamic torque, effectively self-righting them 20 milliseconds into the jump, the fastest of any wingless organism. They land on a collophore, an appendage particular to the springtail that holds water.

Springtails are part of the Collembola family, organisms that are known for having a hydrophilic collophore, a tube-like structure that holds a water droplet and can adhere to surfaces. The researchers determined this collophore is essential for the springtail to glide on the surface of water and effectively land on its feet without bouncing. With high-speed imaging and a hydrodynamic oscillator force mathematical model — using surface tension, inertia, buoyancy, drag, capillary dissipation, and adhesion forces — the researchers calculated how the springtail takes advantage of its collophore for stable landings that release energy through capillary waves.

“Nobody has ever shown experimentally what the collophore is really for, and we're showing that it’s for their survival,” Ortega-Jiménez said. “They need this for stability, controlling their takeoff but more importantly how to perfectly land like an acrobat.”

After the researchers observed the jump, they found that springtails could control their takeoff angle and speed. They broke it down into a mathematical model to determine how precise these jumps were in a computer simulation. The model suggested that if springtails can control the angle of their body, they can glide on the surface of the water with their collophore, validating Ortega’s experimental observations.  

Researchers explored the self-righting ability of springtails by using dead and living springtails in a wind tunnel, as well as using freefall physical models. They found that the springtails' U-shaped posture and a droplet collected by the collophore create the perfect landing.  

“This work shows just how important controlled motion is for predator escape and survival,” said Kathryn Dickson, a program director at the National Science Foundation, which partially funded the research. “Springtails could not have become the most abundant non-insect hexapod without being able to control their gymnast-like escape response. In addition to being fascinating to watch, this new understanding of the biomechanics of how springtails control their jump, spin in midair, and land safely on water could lead to advances in fields from robotics to aerodynamics.”

Next, the researchers built small robots to replicate their experimental and computational observations in a physical environment in collaboration with Professor Jesung-Koh’s team at Ajou University in South Korea.

“It has been a major challenge for jumping robots, specifically at small scales, to control their orientation in the air for landing and jumping,” Koh said. “The finding in this research could inspire insect-scale jumping robots that are able to land safely and expand the capability of robots in new terrains, such as the open-water surfaces in our planet’s lakes and oceans.”

The researchers created a small robot with drag flappers to validate the observations that a collophore and body shape are needed to land.

“We show in three different cases that the native robot spins out of control and lands unpredictably,” Bhamla said. “But as you add each of these increments, like the drag flappers, we demonstrate the robot can achieve stability and land on its feet.”

The robot has a 75% success rate, compared to the springtail’s 85% success rate, making the results significant. But the results could have implications for more than just springtails.

“We are now opening this Pandora's box of what smaller animals can do,” Ortega-Jiménez said. “There is a belief that because they are tiny, they don't have as much control as big animals do. So, we are opening some possibilities of control at this small scale that could give insights into the origins of flight in organisms.”

---

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2211283119 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Directional takeoff, aerial righting, and adhesion landing of semiaquatic springtails

ARTICLE PUBLICATION DATE

7-Nov-2022

Dementia prevalence is declining among older Americans, study finds

Study also finds decreases in disparities based on race and sex

Peer-Reviewed Publication

RAND CORPORATION

The prevalence of dementia in the U.S. is declining among people over age 65, dropping 3.7 percentage points from 2000 to 2016, according to a new RAND Corporation study.

The age-adjusted prevalence of dementia declined from 12.2% of people over age 65 in 2000 to 8.5% of people over age 65 in 2016 – a nearly one-third drop from the 2000 level. The prevalence of dementia decreased over the entire period, but the rate of decline was more rapid between 2000 and 2004.

Differences in the prevalence of dementia between Black men and white men narrowed, with the prevalence of dementia dropping by 7.3 percentage points among Black men as compared to 2.7 percentage points among white men.

The findings are published in the latest edition of the journal Proceedings of the National Academy of Sciences.

“The reason for the decline in the prevalence of dementia are not certain, but this trend is good news for older Americans and the systems that support them,” said Péter Hudomiet, the study's lead author and an economist at RAND, a nonprofit research organization. “This decline may help reduce the expected strain on families, nursing homes and other support systems as the American population ages.”

Michael D. Hurd and Susann Rohwedder of RAND are co-authors of the study

The prevalence of dementia was higher among women than men over the entire period, but the difference shrank between 2000 and 2016. Among men, the prevalence of dementia decreased by 3.2 percentage points from 10.2% to 7.0%. The decrease was larger among women -- 3.9 percentage points from 13.6% to 9.7%.

In 2021, about 6.2 million U.S. adults aged 65 or older lived with dementia. Because age is the strongest risk factor for dementia, it has been predicted that increasing life expectancies will substantially increase the prevalence of Alzheimer’s disease and related dementias from about 50 million to 150 million worldwide by 2050.

However, there is growing evidence that age-adjusted dementia prevalence has been declining in developed countries, possibly because of rising levels of education, a reduction in smoking, and better treatment of key cardiovascular risk factors such as high blood pressure.

Any change in these age-specific rates has important implications for projected prevalence and associated costs, such as payments for nursing care by households, insurance companies, and the government.

The new RAND study employs a novel model to assess cognitive status based on a broad set of cognitive measures elicited from more than 21,000 people who participate in the national Health and Retirement Study, a large population-representative survey that has been fielded for more than two decades.

The model increases the precision of dementia classification by using the longitudinal dimension of the data. Importantly for the study of inequality, the model is constructed to ensure the dementia classification is calibrated within population subgroups and, therefore, it is equipped to produce accurate estimates of dementia prevalence by age, sex, education, race and ethnicity, and by a measure of lifetime earnings.

The RAND study found that education was an important factor that contributed, in a statistical sense, to the reduction in dementia, explaining about 40% of the reduction in dementia prevalence among men and 20% of the reduction among women.

The fraction of college-educated men in the study increased from 21.5% in 2000 to 33.7% in 2016, and the fraction of college-educated women increased from 12.3% to 23% over this period.

Trends in the level of education differ across demographic groups, which may affect inequalities in dementia in the future. For example, while women traditionally had lower levels of education than men, among younger generations, women are more educated. While racial and ethnic minority groups still have lower education levels than non-Hispanic White individuals, the gaps across racial and ethnic groups have shrunk.

“Closing the education gap across racial and ethnic groups may be a powerful tool to reduce health inequalities in general and dementia inequalities in particular, an important public health policy goal,” Hudomiet said.

The age-adjusted prevalence of dementia tended to be higher among racial and ethnic minority individuals, both among men and women. However, among men, the difference in the prevalence between non-Hispanic Black and White individuals narrowed while it remained stable among women. Among non-Hispanic White men, the prevalence of dementia decreased from 9.3% to 6.6%. Among non-Hispanic Black men, the rate fell from 17.2% to 9.9%.

Support for the study, which is titled “Trends in Inequalities in the Prevalence of Dementia in the U.S.,” was provided by a grant from National Institute on Aging.

The RAND Social and Economic Well-Being division seeks to actively improve the health, social and economic well-being of populations and communities throughout the world.

---

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2212205119 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Trends in inequalities in the prevalence of dementia in the United States

ARTICLE PUBLICATION DATE

7-Nov-2022

In ironic twist, CRISPR system used to befuddle bacteria

Peer-Reviewed Publication

NORTH CAROLINA STATE UNIVERSITY

 

IMAGE: BRACHYPODIUM DISTACHYON PLANT GROWN ON LIQUID MEDIA. view more 

CREDIT: PHOTO COURTESY OF MARTA TORRES, M-CAFES POSTDOCTORAL RESEARCHER, DEUTSCHBAUER LAB, ENVIRONMENTAL GENOMICS AND SYSTEMS BIOLOGY "© THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, LAWRENCE BERKELEY NATIONAL LABORATORY."

Call it a CRISPR conundrum.

Bacteria use CRISPR-Cas systems as adaptive immune systems to withstand attacks from enemies like viruses. These systems have been adapted by scientists to remove or cut and replace specific genetic code sequences in a variety of organisms. 

But in a new study, North Carolina State University researchers show that viruses engineered with a CRISPR-Cas system can thwart bacterial defenses and make selective changes to a targeted bacterium – even when other bacteria are in close proximity.

“Viruses are very good at delivering payloads. Here, we use a bacterial virus, a bacteriophage, to deliver CRISPR to bacteria, which is ironic because bacteria normally use CRISPR to kill viruses,” said Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor of Food, Bioprocessing and Nutrition Sciences at NC State and corresponding author of a paper describing the research published today in Proceedings of the National Academy of Sciences. “The virus in this case targets E. coli by delivering DNA to it. It’s like using a virus as a syringe.”

The NC State researchers deployed two different engineered bacteriophages to deliver CRISPR-Cas payloads for targeted editing of E. coli, first in a test tube and then within a synthetic soil environment created to mimic soil – a complex environment that can harbor many types of bacteria. 

Both the engineered bacteriophages, called T7 and lambda, successfully found and then delivered payloads to the E. coli host on the lab bench. These payloads expressed bacterial florescent genes and manipulated the bacterium’s resistance to an antibiotic. 

The researchers then used lambda to deliver a so-called cytosine base editor to the E. coli host. Rather than CRISPR’s sometimes harsh cleaving of DNA sequences, this base editor changed just one letter of E. coli’s DNA, showing the sensitivity and precision of the system. These changes inactivated certain bacterial genes without making other changes to E. coli.

“We used a base editor here as a kind of programmable on-off switch for genes in E. coli. Using a system like this, we can make highly precise single-letter changes to the genome without the double-strand DNA breakage commonly associated with CRISPR-Cas targeting,” said Matthew Nethery, a former NC State Ph.D. student and lead author of the study.

Finally, the researchers demonstrated on-site editing through the use of a fabricated ecosystem (EcoFAB) loaded with a synthetic soil medium of sand and quartz, along with liquid, to mimic a soil environment. The researchers also included three different types of bacteria to test if the phage could specifically locate E. coli within the system. 

“In a lab, scientists can oversimplify things,” Barrangou said. “It’s preferable to model environments, so rather than soup in a test tube, we wanted to examine real-life environments.”

The researchers inserted lambda into the fabricated ecosystem. It showed good efficiency in finding E. coli and making the targeted genetic changes.

“This technology is going to enable our team and others to discover the genetic basis of key bacterial interactions with plants and other microbes within highly controlled laboratory environments such as EcoFABs,” said Trent Northen, a scientist at the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) who collaborates with Barrangou.

“We see this as a mechanism to aid the microbiome. We can make a change to a particular bacterium and the rest of the microbiome remains unscathed,” Barrangou said. “This is a proof of concept that could be employed in any complex microbial community, which could translate into better plant health and better gastrointestinal tract health – environments of importance to food and health.

“Ultimately this study represents the next chapter of CRISPR delivery – using viruses to deliver CRISPR machinery in a complex environment.”

The researchers plan to further this work by testing the phage CRISPR technique with other soil-associated bacteria. Importantly, this illustrates how soil microbial communities can be manipulated to control the composition and function of bacteria associated with plants in fabricated ecosystems to understand how to enhance plant growth and promote plant health, which is of broad interest for sustainable agriculture. 

Funding was provided by m-CAFEs Microbial Community Analysis & Functional Evaluation in Soils, a Science Focus Area led by Lawrence Berkeley National Laboratory and supported by the U.S. Dept. of Energy under contract no. DE-AC02-05CH11231, with collaborative efforts including UC Berkeley and the Innovative Genomics Institute. Co-authors of the paper include Nethery, former NC State post-doctoral researcher Claudio Hidalgo-Cantabrana and NC State graduate student Avery Roberts.

-kulikowski-

Note to editors: The abstract of the paper follows.
      
“CRISPR-based engineering of phages for in situ bacterial base editing”
 

Authors: Matthew A. Nethery, Claudio Hidalgo-Cantabrana, Avery Roberts, Rodolphe Barrangou, NC State University

Published: Nov. 7, 2022 in Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2206744119

Abstract: Investigation of microbial gene function is essential to the elucidation of ecological roles and complex genetic interactions that take place in microbial communities. While microbiome studies have increased in prevalence, the lack of viable in situ editing strategies impedes experimental design and progress, rendering genetic knowledge and manipulation of microbial communities largely inaccessible. Here, we demonstrate the utility of phage-delivered CRISPR-Cas payloads to perform targeted genetic manipulation within a community context deploying a fabricated ecosystem (EcoFAB) as an analog for the soil microbiome. First, we detail the engineering of two classical phages for community editing using recombination to replace non-essential genes through Cas9-based selection. We show efficient engineering of T7, then demonstrate expression of antibiotic resistance and fluorescent genes from an engineered lambda prophage within an Escherichia coli host. Expanding on this, we modify lambda to express an APOBEC-1-based cytosine base editor (CBE), which we leverage to perform C to T point mutations guided by a Cas9 modified to contain only a single active nucleolytic domain (nCas9). We strategically introduced these base substitutions to create premature stop codons in-frame, inactivating both chromosomal (lacZ) and plasmid-encoded genes (mCherry and ampicillin resistance) without perturbation of the surrounding genomic regions. Further, using a multi-genera synthetic soil community, we employed phage-assisted base editing to induce host-specific phenotypic alterations in a community context both in vitro and within the EcoFAB, observing editing efficiencies from 10% to 28% across the bacterial population. The concurrent use of a synthetic microbial community, soil matrix, and EcoFAB device provides a controlled and reproducible model to more closely approximate in situ editing of the soil microbiome.

---

JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2206744119 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

CRISPR-based engineering of phages for in situ bacterial base editing

ARTICLE PUBLICATION DATE

11-Nov-2022

COI STATEMENT

R.B. is a co-founder of Intellia Therapeutics, Locus Biosciences, TreeCo, CRISPR Biotechnologies and Ancilia Biosciences, and a shareholder of Caribou Biosciences, Inari Ag, Felix Biotechnologies, and Provaxus. C.H.-C. is a co-founder of Microviable Therapeutics and shareholder of CRISPR Biotechnologies.