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Researchers create a bodywide map of molecular changes linked to exercise and health

A Stanford Medicine-led effort to learn more about exercise’s molecular effects paints the broadest picture yet of why, in the health arena, sweat is king.

May 1, 2024 - By Krista Conger

Researchers at Stanford Medicine and their colleagues conducted nearly 10,000 measurements in nearly 20 types of tissues, learning about the   effects of exercise on the immune system, stress response, energy production and metabolism. Alan Poulson Photography/Shutterstock.com

Exercise. It’s associated with increased muscle strength, improved heart health, lower blood sugar and just about every other physical improvement you can name. But how does regularly puffing away on a treadmill, biking up a steep hill or going for a brisk lunchtime walk confer such a dizzying array of health benefits?

We’re now closer to finding out, thanks to a vast new study led by Stanford Medicine. Researchers conducted nearly 10,000 measurements in nearly 20 types of tissues to uncover the effect of eight weeks of endurance exercise in laboratory rats trained to run on rodent-sized treadmills.

Their results highlight striking effects of exercise on the immune system, stress response, energy production and metabolism. They uncovered significant links between exercise, molecules and genes already known to be involved in myriad human diseases and tissue recovery.

The study is one of a series of papers published May 1 by members of a multicenter research group meant to lay the groundwork for understanding — on a bodywide, molecular level — exactly how our tissues and cells react when we push them to perform.

“We all know exercise is beneficial for us,” said professor of pathology Stephen Montgomery , PhD. “But we don’t know much about the molecular signals that manifest across the body when people exercise, or how they may change when people train. Our study is the first to take a holistic, bodywide look at molecular changes, from proteins to genes to metabolites to fats and energy production. It’s the broadest profiling yet of the effects of exercise, and it creates an essential map to how it changes the body.”

Montgomery, who is also a professor of genetics and of biomedical data science, is a senior author of the  paper , which published on May 1 in  Nature . Other senior authors are  Michael Snyder , PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics, and associate professor of medicine  Matthew Wheeler , MD. First authors are former genetics PhD student Nicole Gay, PhD; former postdoctoral scholar David Amar, PhD; and Pierre Jean Beltran, PhD, a former postdoctoral scholar at the Broad Institute.

Additional papers by Stanford Medicine researchers include a related published report in  Nature Communications  investigating the effect of exercise-induced changes in genes and tissues known to be involved in disease risk as well as a  paper  published on May 2 in  Cell Metabolism , which focuses on the effects of exercise on the cellular energy factors called mitochondria in various tissues. Montgomery is the senior author of the  Nature Communications  paper and postdoctoral scholar  Nikolai Vetr , PhD, is its lead author. Instructor of cardiovascular medicine  Malene Lindholm , PhD, is the senior author of the  Cell Metabolism  paper, and Amar is the lead author.

Stephen Montgomery

“These papers further highlight the multiple impacts exercise training has on metabolism and health,” Montgomery said.

A coordinated look at exercise

The researchers involved in the study and the other simultaneous publications are part of a national group called the Molecular Transducers of Physical Activity Consortium, or MoTrPAC, organized by the National Institutes of Health. The effort was launched in 2015 to investigate in detail exactly how physical exercise improves health and prevents disease.

The Stanford Medicine team took on a lot of the heavy lifting, studying the effects of eight weeks of endurance training on gene expression (the transcriptome), proteins (the proteome), fats (the lipidome), metabolites (the metabolome), the pattern of chemical tags placed on DNA (the epigenome), the immune system (the…you get the idea).

Let’s just call it the sweat-ome.

They performed 9,466 analyses on multiple tissues in rats as the animals were trained to run increasing distances and compared the results with those of rats that loafed about in their cages. They paid special attention to the muscles of the leg, the heart, the liver, the kidney and a type of fat called white adipose tissue (the kind of fat that accumulates as pounds pile on); other tissues included the lungs, brain and brown adipose tissue (a more metabolically active type of fat that helps burn calories). The combination of multiple assays — think of all those -omes! — and tissue types pumped out results numbering in the hundreds of thousands for non-epigenetic changes to more than 2 million distinct changes in the epigenome. The results will keep scientists hopping for years.

Although this study served primarily to create a database for future analysis, some interesting nuggets vaulted to the top. First, they noted that the expression of 22 genes changed with exercise in all six of the tissues they focused on. Many of these genes were involved in what are known as heat shock pathways, which stabilize the structure of proteins when cells undergo stress including changes in temperature (feel that burn?), infection or tissue remodeling (hello new muscle fibers!). Others have been implicated in pathways that reduce blood pressure and increase the body’s sensitivity to insulin, which lowers blood sugar levels.

The researchers also noted that the expression of several genes involved in Type 2 diabetes, heart disease, obesity and kidney disease was reduced in exercising rats as compared with their sedentary counterparts — a clear link between their studies and human health.

Sex differences

Finally, they identified sex differences in how multiple tissues in male and female rats responded to exercise. Male rats lost about 5% of their body fat after eight weeks of exercise while female rats didn’t lose a significant amount. (They did, however, maintain their starting fat percentage while the sedentary females packed on an additional 4% of body fat during the study period.) But the largest difference was observed in gene expression in the rats’ adrenal glands. After one week, genes associated with the generation of steroid hormones like adrenaline and with energy production increased in male rats but decreased in female rats.

Despite these early, tantalizing associations, the researchers caution that exercise science is nowhere near the finish line. It’s more like the starting gun has just fired. But the future is exciting.

“In the long term, it’s unlikely we will find any one magic intervention that reproduces what exercise can do for a person,” Montgomery said. “But we might get closer to the idea of precision exercise — tailoring recommendations based on a person’s genetics, sex, age or other health conditions to generate beneficial whole-body responses.”

A full list of researchers and institutions involved in the study can be found online.

The MoTrPAC study is supported by the National Institutes of Health (grants U24OD026629, U24DK112349, U24DK112342, U24DK112340, U24DK112341, U24DK112326, 612 U24DK112331, U24DK112348, U01AR071133, U01AR071130, 613 U01AR071124, U01AR071128, U01AR071150, U01AR071160, U01AR071158, U24AR071113, U01AG055133, U01AG055137, 615 U01AG055135, 5T32HG000044, P30AG044271 and P30AG003319), the National Science Foundation, and the Knut and Alice Wallenberg Foundation.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Science News

These are the most-read science news stories of 2021.

The International Space Station spotted the origins of a bizarre type of upside-down lightning called a blue jet (illustrated) zipping up from a thundercloud into the stratosphere in 2019. The discovery ranked among  Science News ' most-read stories of 2021.

DTU SPACE, DANIEL SCHMELLING/MOUNT VISUAL

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By Science News Staff

December 23, 2021 at 9:00 am

Science News drew over 21 million visitors to our website this year. Here’s a rundown of the most-read news stories and long reads of 2021.

Top news stories

1. space station detectors found the source of weird ‘blue jet’ lightning.

Instruments on the International Space Station detected the origins of an odd type of lightning called a blue jet. The bizarre bolt is sparked by a “blue bang” — a flash of bright blue light that may be brought on by the turbulent mixing of oppositely charged regions within a thundercloud ( SN: 2/13/21, p. 14 ).

2. A newfound quasicrystal formed in the first atomic bomb test

The first atomic bomb test, in 1945, forged a peculiar, glassy material called trinitite — and within it, a rare form of matter called a quasicrystal . Quasicrystals’ atoms are arranged in an orderly structure like normal crystals, but the structure’s pattern doesn’t repeat ( SN: 6/19/21, p. 12 ).

3. An Indigenous people in the Philippines have the most Denisovan DNA

The Ayta Magbukon people in the Philippines set the record for the highest known level of Denisovan ancestry — about 5 percent of their DNA comes from the ancient hominids . The finding suggests that several Denisovan populations independently reached Southeast Asia and interbred with Homo sapiens groups that arrived thousands of years later ( SN: 9/11/21, p. 16 ).

4. Astronomers may have seen a star gulp down a black hole and explode

In a first, astronomers caught a glimpse of a rare double cosmic cannibalism : A star swallowed a black hole or neutron star, which then gobbled that star from within, resulting in an astonishing explosion ( SN: 10/9/21 & 10/23/21, p. 6 ).

5. Frog skin cells turned themselves into living machines

Skin stem cells plucked from frog embryos organized themselves into miniature living robots, dubbed “xenobots,” that can swim, move around debris and even self-heal . Xenobots may one day serve a useful purpose, but ethical questions need to be considered ( SN: 4/24/21, p. 8 ).

Favorite video

Acrobatic rabbits bewitched online readers in our most-viewed YouTube video posted this year. The video — accompanying the story “ A gene defect may make rabbits do handstands instead of hop ” ( SN: 4/24/21, p. 13 ) — shows a sauteur d’Alfort rabbit walking on its front paws (below). Such hop-less bunnies may have adopted the odd gait because of a mutation in a gene called RORB , scientists discovered.

Top feature stories

1. new drugs that block a brain chemical are game changers for some migraine sufferers.

A class of drugs that inhibits a neurotransmitter called calcitonin gene-related peptide is helping some patients who suffer from chronic, debilitating migraines ( SN: 3/27/21, p. 16 ).

2. Einstein’s theory of general relativity unveiled a dynamic and bizarre cosmos

Albert Einstein’s general theory of relativity has served as the bedrock of our understanding of the cosmos. In the last 100 years, scientists have confirmed its most radical predictions, including black holes, gravitational waves and an expanding universe ( SN: 2/13/21, p. 16 ).

3. Chemists are reimagining recycling to keep plastics out of landfills

No matter people’s dedication to sorting and recycling plastics, most still end up in landfills because the materials are too difficult to transform into useful new products. Some chemists are trying to change that ( SN: 1/30/21, p. 20 ).

4. Psychology has struggled for a century to make sense of the mind

In the last 100 years, psychologists and other social scientists have dug into the muddy “science of us” and developed conflicting theories about human thought and behavior. From the messy, contentious research bloomed insights into what makes humans tick ( SN: 8/14/21, p. 18 ).

5. Fossils and ancient DNA paint a vibrant picture of human origins

From the Taung Child to Lucy, the last century of paleoanthropology has sketched a rough timeline of how humans came to be. Scientists now agree that human evolution has its roots in Africa, but many mysteries in our history remain to be solved ( SN: 9/25/21, p. 20 ).

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Scientists push new paradigm of animal consciousness, saying even insects may be sentient

Bees play by rolling wooden balls — apparently for fun . The cleaner wrasse fish appears to recognize its own visage in an underwater mirror . Octopuses seem to react to anesthetic drugs and will avoid settings where they likely experienced past pain. 

All three of these discoveries came in the last five years — indications that the more scientists test animals, the more they find that many species may have inner lives and be sentient. A surprising range of creatures have shown evidence of conscious thought or experience, including insects, fish and some crustaceans. 

That has prompted a group of top researchers on animal cognition to publish a new pronouncement that they hope will transform how scientists and society view — and care — for animals. 

Nearly 40 researchers signed “ The New York Declaration on Animal Consciousness ,” which was first presented at a conference at New York University on Friday morning. It marks a pivotal moment, as a flood of research on animal cognition collides with debates over how various species ought to be treated. 

The declaration says there is “strong scientific support” that birds and mammals have conscious experience, and a “realistic possibility” of consciousness for all vertebrates — including reptiles, amphibians and fish. That possibility extends to many creatures without backbones, it adds, such as insects, decapod crustaceans (including crabs and lobsters) and cephalopod mollusks, like squid, octopus and cuttlefish.

“When there is a realistic possibility of conscious experience in an animal, it is irresponsible to ignore that possibility in decisions affecting that animal,” the declaration says. “We should consider welfare risks and use the evidence to inform our responses to these risks.” 

Jonathan Birch, a professor of philosophy at the London School of Economics and a principal investigator on the Foundations of Animal Sentience project, is among the declaration’s signatories. Whereas many scientists in the past assumed that questions about animal consciousness were unanswerable, he said, the declaration shows his field is moving in a new direction. 

“This has been a very exciting 10 years for the study of animal minds,” Birch said. “People are daring to go there in a way they didn’t before and to entertain the possibility that animals like bees and octopuses and cuttlefish might have some form of conscious experience.”

From 'automata' to sentient

There is not a standard definition for animal sentience or consciousness, but generally the terms denote an ability to have subjective experiences: to sense and map the outside world, to have capacity for feelings like joy or pain. In some cases, it can mean that animals possess a level of self-awareness. 

In that sense, the new declaration bucks years of historical science orthodoxy. In the 17th century, the French philosopher René Descartes argued that animals were merely “material automata” — lacking souls or consciousness.

Descartes believed that animals “can’t feel or can’t suffer,” said Rajesh Reddy, an assistant professor and director of the animal law program at Lewis & Clark College. “To feel compassion for them, or empathy for them, was somewhat silly or anthropomorphizing.” 

In the early 20th century, prominent behavioral psychologists promoted the idea that science should only study observable behavior in animals, rather than emotions or subjective experiences . But beginning in the 1960s, scientists started to reconsider. Research began to focus on animal cognition, primarily among other primates. 

Birch said the new declaration attempts to “crystallize a new emerging consensus that rejects the view of 100 years ago that we have no way of studying these questions scientifically.” 

Indeed, a surge of recent findings underpin the new declaration. Scientists are developing new cognition tests and trying pre-existing tests on a wider range of species, with some surprises. 

Take, for example, the mirror-mark test, which scientists sometimes use to see if an animal recognizes itself. 

In a series of studies, the cleaner wrasse fish seemed to pass the test . 

The fish were placed in a tank with a covered mirror, to which they exhibited no unusual reaction. But after the cover was lifted, seven of 10 fish launched attacks toward the mirror, signaling they likely interpreted the image as a rival fish. 

After several days, the fish settled down and tried odd behaviors in front of the mirror, like swimming upside down, which had not been observed in the species before. Later, some appeared to spend an unusual amount of time in front of the mirror, examining their bodies. Researchers then marked the fish with a brown splotch under the skin, intended to resemble a parasite. Some fish tried to rub the mark off. 

“The sequence of steps that you would only ever have imagined seeing with an incredibly intelligent animal like a chimpanzee or a dolphin, they see in the cleaner wrasse,” Birch said. “No one in a million years would have expected tiny fish to pass this test.”

In other studies, researchers found that zebrafish showed signs of curiosity when new objects were introduced into their tanks and that cuttlefish could remember things they saw or smelled . One experiment created stress for crayfish by electrically shocking them , then gave them anti-anxiety drugs used in humans. The drugs appeared to restore their usual behavior.

Birch said these experiments are part of an expansion of animal consciousness research over the past 10 to 15 years. “We can have this much broader canvas where we’re studying it in a very wide range of animals and not just mammals and birds, but also invertebrates like octopuses, cuttlefish,” he said. “And even increasingly, people are talking about this idea in relation to insects.”

As more and more species show these types of signs, Reddy said, researchers might soon need to reframe their line of inquiry altogether: “Scientists are being forced to reckon with this larger question — not which animals are sentient, but which animals aren’t?” 

New legal horizons

Scientists’ changing understanding of animal sentience could have implications for U.S. law, which does not classify animals as sentient on a federal level, according to Reddy. Instead, laws pertaining to animals focus primarily on conservation, agriculture or their treatment by zoos, research laboratories and pet retailers.

“The law is a very slow moving vehicle and it really follows societal views on a lot of these issues,” Reddy said. “This declaration, and other means of getting the public to appreciate that animals are not just biological automatons, can create a groundswell of support for raising protections.” 

State laws vary widely. A decade ago, Oregon passed a law recognizing animals as sentient and capable of feeling pain, stress and fear, which Reddy said has formed the bedrock of progressive judicial opinions in the state.  

Meanwhile, Washington and California are among several states where lawmakers this year have considered bans on octopus farming, a species for which scientists have found strong evidence of sentience. 

British law was recently amended to consider octopuses sentient beings — along with crabs and lobsters .

“Once you recognize animals as sentient, the concept of humane slaughter starts to matter, and you need to make sure that the sort of methods you’re using on them are humane,” Birch said. “In the case of crabs and lobsters, there are pretty inhumane methods, like dropping them into pans of boiling water, that are very commonly used.”

Evan Bush is a science reporter for NBC News. He can be reached at [email protected].

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Science communication competition brings research into the real world

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Laurence Willemet remembers countless family dinners where curious faces turned to her with shades of the same question: “What is it, exactly, that you do with robots?”

It’s a familiar scenario for MIT students exploring topics outside of their family’s scope of knowledge — distilling complex concepts without slides or jargon, plumbing the depths with nothing but lay terms. “It was during these moments,” Willemet says, “that I realized the importance of clear communication and the power of storytelling.”

Participating in the MIT Research Slam, then, felt like one of her family dinners.

The finalists in the 2024 MIT Research Slam competition met head-to-head on Wednesday, April 17 at a live, in-person showcase event. Four PhD candidates and four postdoc finalists demonstrated their topic mastery and storytelling skills by conveying complex ideas in only 180 seconds to an educated audience unfamiliar with the field or project at hand.

The Research Slam follows the format of the 3-Minute Thesis competition, which takes place annually at over 200 universities around the world. Both an exciting competition and a rigorous professional development training opportunity, the event serves an opportunity to learn for everyone involved.

One of this year’s competitors, Bhavish Dinakar, explains it this way: “Participating in the Research Slam was a fantastic opportunity to bring my research from the lab into the real world. In addition to being a helpful exercise in public speaking and communication, the three-minute time limit forces us to learn the art of distilling years of detailed experiments into a digestible story that non-experts can understand.”

Leading up to the event, participants joined training workshops on pitch content and delivery, and had the opportunity to work one-on-one with educators from the Writing and Communication Center, English Language Studies, Career Advising and Professional Development, and the Engineering Communication Labs, all of which co-sponsored and co-produced the event. This interdepartmental team offered support for the full arc of the competition, from early story development to one-on-one practice sessions.

The showcase was jovially emceed by Eric Grunwald, director of English language learning. He shared his thoughts on the night: “I was thrilled with the enthusiasm and skill shown by all the presenters in sharing their work in this context. I was also delighted by the crowd’s enthusiasm and their many insightful questions. All in all, another very successful slam.”

A panel of accomplished judges with distinct perspectives on research communication gave feedback after each of the talks: Deborah Blum, director of the Knight Science Journalism Program at MIT; Denzil Streete, senior associate dean and director of graduate education; and Emma Yee, scientific editor at the journal Cell .

Deborah Blum aptly summed up her experience: “It was a pleasure as a science journalist to be a judge and to listen to this smart group of MIT grad students and postdocs explain their research with such style, humor, and intelligence. It was a reminder of the importance the university places on the value of scientists who communicate. And this matters. We need more scientists who can explain their work clearly, explain science to the public, and help us build a science-literate world.”

After all the talks, the judges provided constructive and substantive feedback for the contestants. It was a close competition, but in the end, Bhavish Dinakar was the judges’ choice for first place, and the audience agreed, awarding him the Audience Choice award. Omar Rutledge’s strong performance earned him the runner-up position. Among the postdoc competitors, Laurence Willemet won first place and Audience Choice, with Most Kaniz Moriam earning the runner-up award.

Postdoc Kaniz Mariam noted that she felt privileged to participate in the showcase. “This experience has enhanced my ability to communicate research effectively and boosted my confidence in sharing my work with a broader audience. I am eager to apply the lessons learned from this enriching experience to future endeavors and continue contributing to MIT's dynamic research community. The MIT Research Slam Showcase wasn't just about winning; it was about the thrill of sharing knowledge and inspiring others. Special thanks to Chris Featherman and Elena Kallestinova from the MIT Communication Lab for their guidance in practical communication skills. ”

Double winner Laurence Willemet related the competition to experiences in her daily life. Her interest in the Research Slam was rooted in countless family dinners filled with curiosity. “‘What is it exactly that you do with robots?’ they would ask, prompting me to unravel the complexities of my research in layman’s terms. Each time, I found myself grappling with the task of distilling intricate concepts into digestible nuggets of information, relying solely on words to convey the depth of my work. It was during these moments, stripped of slides and scientific jargon, that I realized the importance of clear communication and the power of storytelling. And so, when the opportunity arose to participate in the Research Slam, it felt akin to one of those family dinners for me.”

The first place finishers received a $600 cash prize, while the runners-up and audience choice winners each received $300.

Last year’s winner in the PhD category, Neha Bokil, candidate in biology working on her dissertation in the lab of David Page, is set to represent MIT at the Three Minute Thesis Northeast Regional Competition later this month, which is organized by the Northeastern Association of Graduate Schools.

A full list of slam finalists and the titles of their talks is below.

  PhD Contestants: 

• Pradeep Natarajan, Chemical Engineering (ChemE), “What can coffee-brewing teach us about brain disease?”
• Omar Rutledge, Brain and Cognitive Sciences, “Investigating the effects of cannabidiol (CBD) on social anxiety disorder”
• Bhavish Dinakar, ChemE, “A boost from batteries: making chemical reactions faster”
• Sydney Dolan, Aeronautics and Astronautics, “Creating traffic signals for space”

  Postdocs: 

• Augusto Gandia, Architecture and Planning, “Cyber modeling — computational morphogenesis via ‘smart’ models”
• Laurence Willemet, Computer Science and Artificial Intelligence Laboratory, “Remote touch for teleoperation”
• Most Kaniz Moriam, Mechanical Engineering, “Improving recyclability of cellulose-based textile wastes”
• Mohammed Aatif Shahab, ChemE, “Eye-based human engineering for enhanced industrial safety” 

Research Slam organizers included Diana Chien, director of MIT School of Engineering Communication Lab ; Elena Kallestinova, director of MIT Writing and Communication Center ; Alexis Boyer, assistant director, Graduate Career Services, Career Advising and Professional Development (CAPD); Amanda Cornwall, associate director, Graduate Student Professional Development, CAPD; and Eric Grunwald, director of English Language Studies. This event was sponsored by the Office of Graduate Education, the Office of Postdoctoral Services, the Writing and Communication Center, MIT Career Advising and Professional Development , English Language Studies, and the MIT School of Engineering Communication Labs.

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• MIT School of Engineering Communication Lab
• MIT English Language Studies

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Environmental Factor

Your online source for niehs news, data science event showcases new approaches to environmental health.

NC State symposium highlighted state-of-the-art methods and research activities using big data to advance environmental health studies.

By Ben Richardson

Researchers and big data specialists from across the country, including NIEHS grantees, gathered at North Carolina State University (NC State) April 5 for the Data Science and Environmental Health Science Research Symposium . Sponsored in part by two NIEHS-funded centers, the Center for Environmental and Health Effects of PFAS and the Center for Human Health and the Environment, the event was designed to foster collaborative discussion and present cutting-edge work in the field of data science.

During the daylong gathering, hosted by NC State Professor Seth Kullman, Ph.D. , attendees shared their research, participated in poster sessions, and networked with fellow scientists. Topics varied from addressing environmental health disparities through data mining to new methods in population genomics, which involves providing hazard and risk assessments without animal testing.

NIEHS Director Rick Woychik, Ph.D. , kicked off the day by outlining the institute’s strategic priorities: the exposome, precision environmental health, mechanistic toxicology/biology, climate change and health, environmental justice, and — particularly relevant to the symposium’s theme — data science.

“There’s a lot of data management that’s going to have to happen if environmental health science is to move forward systematically,” Woychik said. “But how do we develop infrastructure that is robust, avoids duplication, and allows us to test hypotheses? That’s the problem for us to solve.”

Meeting the big data challenge

In her keynote address, Francesca Dominici, Ph.D. , a professor of biostatistics at the Harvard T.H. Chan School of Public Health and NIEHS grantee, responded to this challenge. In particular, she described how her team was using innovative data science methods to change environmental policy.

Prior to February, the air quality limit set by the Environmental Protection Agency (EPA) for fine particulate matter (PM) measuring less than 2.5 microns in diameter (PM2.5) was 12 micrograms per cubic meter . However, Dominici believed that even these levels of pollution could be harmful.

To test this theory, her team compared mortality rates in different Zip codes across the U.S. to PM2.5 levels at each location. They found that every 10 micrograms increase in PM2.5 led to an 11% increase in mortality, even at levels well below the limit of 12 micrograms per cubic meter.

“Based on our research, the EPA raised its standards for fine particulate matter to 9 micrograms per cubic meter,” said Dominici. “This is a big deal, not only because it means we are going to be breathing cleaner air, but also because it showed the impact data science can have on policy.”

Fostering collaborative data science

Following the keynote, the symposium split up into targeted sessions on various subjects. Though each speaker focused on a different topic, many of them highlighted the same underlying theme: the importance of collaboration and data sharing between institutions.

For instance, NIEHS scientist Alison Motsinger-Reif, Ph.D. , called attention to her team’s efforts to provide access to data from the Personalized Environment and Genes Study (PEGS) , which includes health information on more than 9,000 participants.

“We talk a lot about data sharing in our lab, so we decided to create an interactive web tool that can be used to engage directly with PEGS,” she said. “You can download the data, visualize it, and manipulate it. We’re thrilled to have this resource and fully committed to growing it in the future.”

For some participants, making environmental health data more widely accessible was not only a way of helping to promote collaboration, but also a means of producing better science — especially when dealing with complicated phenomena such as gene-environment interactions.

Chirag Patel, Ph.D. , a professor of biomedical informatics at Harvard University, noted that data sharing is particularly crucial for large-scale research projects that seek to differentiate between possible causes of disease within a population.

“We’re at an incredible time in the field of environmental health sciences when we have all these different data sets coming together,” said Patel. “Because of this, we can integrate multidimensional data across a number of measures to try and figure out where the elusive risk is for highly complicated traits.”

(Ben Richardson, Ph.D., is a Presidential Management Fellow in the NIEHS Office of Communications and Public Liaison.)

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Republicans Step Up Attacks on Scientist at Heart of Lab Leak Theory

A heated hearing produced no new evidence that Peter Daszak or his nonprofit, EcoHealth Alliance, were implicated in the Covid outbreak.

By Benjamin Mueller

House Republicans demanded on Wednesday that the president of a virus-hunting nonprofit group be criminally investigated and barred from federal research funds, a sharp escalation in their campaign against scientists in the United States who Republicans have suggested either had links to the origin of the Covid-19 pandemic or obscured its true beginnings.

During a heated three-hour hearing of the Select Subcommittee on the Coronavirus Pandemic, Republican lawmakers at times raised their voices at the nonprofit’s leader, Peter Daszak, and said that they believed that he would fare poorly as a defendant in criminal court.

The nonprofit, EcoHealth Alliance, which receives federal funding to study global threats from wild animal viruses, has faced suspicion over a proposal that it made in 2018 to team up with Chinese scientists on novel coronavirus experiments that Republicans believe could have led to the pandemic, despite that project’s never receiving funding.

But in a report and in extensive questioning on Wednesday, the Republicans offered no new information suggesting that EcoHealth Alliance or Dr. Daszak were involved in the coronavirus outbreak. And they did not produce any evidence pointing directly to a coronavirus leak from a lab in China, with or without EcoHealth’s involvement, a hitch in their yearslong effort to implicate Chinese and American scientists in the beginnings of the pandemic.

Democrats on the subcommittee seized on the dearth of new evidence, even as they echoed Republican concerns that Dr. Daszak had not been forthcoming about his collaborations with Chinese scientists.

The subcommittee, which is led by Republicans, has reviewed nearly a half-million pages of documents and conducted over 100 hours of private interviews in the course of investigating the origin of Covid, Representative Raul Ruiz of California, the panel’s top Democrat, said on Wednesday.

But, Mr. Ruiz said, the subcommittee has found “no evidence” linking the pandemic to EcoHealth’s research. And he added that the investigation had not “meaningfully advanced our understanding of the pandemic’s origins.” Rather, he said, the subcommittee’s work now “appeared to be an effort to weaponize concerns about a lab-related origin to fuel sentiment against our nation’s scientists and public health officials for partisan gain.”

Republicans, for their part, pledged that their investigation would continue. They have called Dr. Anthony S. Fauci, the former director of the National Institute of Allergy and Infectious Diseases, to testify next month. A Republican member of the subcommittee pushed in January for Dr. Fauci to be jailed .

“I support work that will make the world safer,” the chairman of the subcommittee, Representative Brad Wenstrup of Ohio, a Republican, said as he opened the hearing on Wednesday. “Our concern is that this research and research similar does the opposite,” he said, referring to EcoHealth’s collaborations with Chinese scientists. “It puts the world at the risk of a pandemic.”

Republicans and Democrats alike hammered Dr. Daszak on Wednesday for what they described as a long list of misrepresentations and evasions. They suggested, among other things, that he was being untruthful about why he had been late to submit a required report to health officials before the pandemic and that he had cast research proposals in ways that helped his chances of receiving funding but misled reviewers. Dr. Daszak strongly denied those charges.

Much of the suspicion centered on an EcoHealth request made in 2018 for Defense Department funding to collect and experiment on coronaviruses with novel traits that would make them highly transmissible in humans.

EcoHealth’s proposed partners included the Wuhan Institute of Virology, a premier site for coronavirus research in China. That institute’s presence in the city where the Covid outbreak began was at the heart of theories that the virus had first infected people as a result of research activities.

Republicans said that notes on a draft of the proposal from 2018 suggested Dr. Daszak was trying to mislead American officials about the extent of Chinese involvement in the project. Dr. Daszak denied that, saying that he had sought — and received — approval from American defense officials for Chinese scientists to participate. Dr. Daszak said the research had never been carried out.

“It’s utterly irrelevant to the origins of Covid,” Dr. Daszak said of the proposal. He acknowledged that Wuhan scientists could have been conducting research independently that he was not aware of.

The Wuhan institute’s biosafety practices have intensified concerns about the possibility of a lab leak. On Wednesday, Republicans doubled down on worries about its lab’s protocols, citing private emails and comments in a closed-door congressional interview by Ralph Baric, a virologist at the University of North Carolina who has collaborated with EcoHealth and the Wuhan institute.

In an email to Dr. Daszak in 2021 , Dr. Baric said the Wuhan institute had failed to conduct virus experiments under appropriately safe conditions, and called the idea that they were taking proper precautions a “load of BS.” Still, Dr. Baric told Dr. Daszak in a separate email that year that the coronavirus had most likely jumped from animals to people outside of a lab. He cited the absence of any evidence that the Wuhan institute possessed a virus related closely enough to the one that caused the pandemic.

There remains no evidence that the Wuhan institute stored any virus that could have become the coronavirus and caused Covid, with or without scientific tinkering, researchers have said.

Scientists who specialize in tracing outbreaks have published analyses of early cases and viral genomes that they say point to the pandemic’s starting at an illegal wild-animal market in Wuhan. The presence of the coronavirus in samples from the market containing genetic material linked to raccoon dogs , they have said, is consistent with that scenario.

Dr. Daszak cited animal-borne disease threats on Wednesday in defending projects by EcoHealth, which works with collaborators around the world to identify and study dangerous viruses circulating in nature.

In April 2020, as EcoHealth came under attack from President Donald J. Trump, the group had a grant terminated by the National Institutes of Health. The grant was reinstated last year, but it does not provide funding for any research in China. The Biden administration has also taken steps to impose a 10-year ban on funding for the Wuhan Institute of Virology.

Republicans on Wednesday cited concerns about EcoHealth’s compliance with grant reporting requirements in arguing that EcoHealth, too, should be barred from receiving federal funds. The N.I.H. faulted the group in 2021 for failing to promptly report findings from studies on how well bat coronaviruses grow in mice. An internal federal watchdog agency chided the N.I.H. last year for failing to demand a progress report from EcoHealth that was two years late.

In an interview after the hearing, Mr. Wenstrup, the Republican subcommittee chair, said that oversight by health agencies was too weak. He called for the creation of criminal penalties for violating health agency protocols — “anything from a misdemeanor to a felony,” he said — as a way of better policing certain scientific research.

Benjamin Mueller reports on health and medicine. He was previously a U.K. correspondent in London and a police reporter in New York. More about Benjamin Mueller

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Collection  12 March 2021

2020 Top 50 Life and Biological Sciences Articles

We are pleased to share with you the 50 most downloaded Nature Communications articles* in the life and biological sciences published in 2020. (Please note we have a separate collection on the Top 50 SARS-CoV-2 papers .) Featuring authors from around the world, these papers highlight valuable research from an international community.

Browse all Top 50 subject area collections here .

* Data obtained from SN Insights (based on Digital Science's Dimensions) and has been normalised to account for articles published later in the year.

Vitamin D metabolites and the gut microbiome in older men

Here, the authors investigate associations of vitamin D metabolites with gut microbiome in a cross-sectional analysis of 567 elderly men enrolled in the Osteoporotic Fractures in Men (MrOS) Study and find larger alpha-diversity correlates with high 1,25(OH)2D and high 24,25(OH)2D and higher ratios of activation and catabolism.

• Robert L. Thomas
• Lingjing Jiang
• Deborah M. Kado

The misuse of colour in science communication

The accurate representation of data is essential in science communication, however, colour maps that visually distort data through uneven colour gradients or are unreadable to those with colour vision deficiency remain prevalent. Here, the authors present a simple guide for the scientific use of colour and highlight ways for the scientific community to identify and prevent the misuse of colour in science.

• Fabio Crameri
• Grace E. Shephard
• Philip J. Heron

Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

The gut microbiota may contribute to depression, but the underlying mechanism is not well understood. Here the authors use a mouse model of stress induced depression to demonstrate that behavioural changes conferred by fecal transplant from stressed to naïve mice require the endocannabinoid system.

• Grégoire Chevalier
• Eleni Siopi
• Pierre-Marie Lledo

The default network of the human brain is associated with perceived social isolation

Here, using pattern-learning analyses of structural, functional, and diffusion brain scans in ~40,000 UK Biobank participants, the authors provide population-scale evidence that the default network is associated with perceived social isolation.

• R. Nathan Spreng
• Emile Dimas
• Danilo Bzdok

Non-invasive early detection of cancer four years before conventional diagnosis using a blood test

Patients whose disease is diagnosed in its early stages have better outcomes. In this study, the authors develop a non invasive blood test based on circulating tumor DNA methylation that can potentially detect cancer occurrence even in asymptomatic patients.

• Xingdong Chen
• Jeffrey Gole

Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure

Regulatory and coding regions of genes are shaped by evolution to control expression levels. Here, the authors use deep learning to identify rules controlling gene expression levels and suggest that all parts of the gene regulatory structure interact in this.

• Christoph S. Börlin
• Aleksej Zelezniak

A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

Antibody mediated immunity to SARS-CoV-2 will affect future transmission and disease severity. This systematic review on antibody response to coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and endemic coronaviruses provides insights into kinetics, correlates of protection, and association with disease severity.

• Angkana T. Huang
• Bernardo Garcia-Carreras
• Derek A. T. Cummings

Biomineral armor in leaf-cutter ants

Biomineral armour is known in a number of diverse creatures but has not previously been observed in insects. Here, the authors report on the discovery and characterization of high-magnesium calcite armour which overlays the exoskeletons of leaf-cutter ants.

• Chang-Yu Sun
• Cameron R. Currie

Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation

Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

• Jasper Iske
• Midas Seyda
• Stefan G. Tullius

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

Preclinical evidence suggests that a fasting mimicking diet (FMD) can make cancer cells more vulnerable to chemotherapy, while protecting normal cells. In this randomized phase II clinical trial of 131 patients with HER2 negative early stage breast cancer, the authors demonstrate that FMD is safe and enhances the effects of neoadjuvant chemotherapy on radiological and pathological tumor response.

• Stefanie de Groot
• Rieneke T. Lugtenberg
• Dutch Breast Cancer Research Group (BOOG)

Aerobic microbial life persists in oxic marine sediment as old as 101.5 million years

The discovery of aerobic microbial communities in nutrient-poor sediments below the seafloor begs the question of the mechanisms for their persistence. Here the authors investigate subseafloor sediment in the South Pacific Gyre abyssal plain, showing that aerobic microbial life can be revived and retain metabolic potential even from 101.5 Ma-old sediment.

• Yuki Morono
• Fumio Inagaki

The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice

Auxin-inducible degron systems can be leaky and require high doses of auxin. Here the authors establish AID2 which uses an OsTIR1 mutant and the ligand 5-Ph-IAA to overcome these problems and establish AID-mediated target depletion in mice.

• Aisha Yesbolatova
• Yuichiro Saito
• Masato T. Kanemaki

Origin and cross-species transmission of bat coronaviruses in China

Bats are a likely reservoir of zoonotic coronaviruses (CoVs). Here, analyzing bat CoV sequences in China, the authors find that alpha-CoVs have switched hosts more frequently than betaCoVs, identify a bat family and genus that are highly involved in host-switching, and define hotspots of CoV evolutionary diversity.

• Alice Latinne
• Peter Daszak

Multivariate genomic scan implicates novel loci and haem metabolism in human ageing

Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

• Paul R. H. J. Timmers
• James F. Wilson
• Joris Deelen

A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes

Mircobial symbionts of mosquitoes can affect transmission of human pathogens. Here, Herren et al . identify a microsporidian symbiont in Anopheles gambiae that impairs transmission without affecting mosquito fecundity or survival.

• Jeremy K. Herren
• Lilian Mbaisi
• Steven P. Sinkins

Gene editing and elimination of latent herpes simplex virus in vivo

Herpes simplex virus establishes lifelong latency in ganglionic neurons, which are the source for recurrent infection. Here Aubert et al. report a promising antiviral therapy based on gene editing with adeno-associated virus-delivered meganucleases, which leads to a significant reduction in ganglionic HSV loads and HSV reactivation.

• Martine Aubert
• Daniel E. Strongin
• Keith R. Jerome

A predictive index for health status using species-level gut microbiome profiling

A biologically-interpretable and robust metric that provides insight into one’s health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, the authors introduce a species-level index that predicts the likelihood of having a disease.

• Vinod K. Gupta
• Jaeyun Sung

Bacterial nanotubes as a manifestation of cell death

Bacterial nanotubes and other similar membranous structures have been reported to function as conduits between cells to exchange DNA, proteins, and nutrients. Here the authors provide evidence that bacterial nanotubes are formed only by dead or dying cells, thus questioning their previously proposed functions.

• Jiří Pospíšil
• Dragana Vítovská
• Libor Krásný

Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment

Intermittent fasting (IF) has been shown beneficial in reducing metabolic diseases. Here, using a multi-omics approach in a T2D mouse model, the authors report that IF alters the composition of the gut microbiota and improves metabolic phenotypes that correlate with cognitive behavior.

• Zhigang Liu
• Xiaoshuang Dai

Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells

Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

• Tapash Jay Sarkar
• Marco Quarta
• Vittorio Sebastiano

Mitochondrial TCA cycle metabolites control physiology and disease

Mitochondrial metabolites contribute to more than biosynthesis, and it is clear that they influence multiple cellular functions in a variety of ways. Here, Martínez-Reyes and Chandel review key metabolites and describe their effects on processes involved in physiology and disease including chromatin dynamics, immunity, and hypoxia.

• Inmaculada Martínez-Reyes
• Navdeep S. Chandel

A deep learning model to predict RNA-Seq expression of tumours from whole slide images

RNA-sequencing of tumour tissue can provide important diagnostic and prognostic information but this is costly and not routinely performed in all clinical settings. Here, the authors show that whole slide histology slides—part of routine care—can be used to predict RNA-sequencing data and thus reduce the need for additional analyses.

• Benoît Schmauch
• Alberto Romagnoni
• Gilles Wainrib

Circadian regulation of mitochondrial uncoupling and lifespan

Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

• Matt Ulgherait
• Mimi Shirasu-Hiza

Circadian control of brain glymphatic and lymphatic fluid flow

Glymphatic function is increased during the rest phase while more cerebrospinal fluid (CSF) drains directly to the lymphatic system during the active phase. The water channel aquaporin-4 supports these endogenous, circadian rhythms in CSF distribution.

• Lauren M. Hablitz
• Virginia Plá
• Maiken Nedergaard

Brain-inspired replay for continual learning with artificial neural networks

One challenge that faces artificial intelligence is the inability of deep neural networks to continuously learn new information without catastrophically forgetting what has been learnt before. To solve this problem, here the authors propose a replay-based algorithm for deep learning without the need to store data.

• Gido M. van de Ven
• Hava T. Siegelmann
• Andreas S. Tolias

Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy

Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.

• Charles P. Couturier
• Shamini Ayyadhury
• Kevin Petrecca

Deep learning for genomics using Janggu

Deep learning is becoming a popular approach for understanding biological processes but can be hard to adapt to new questions. Here, the authors develop Janggu, a python library that aims to ease data acquisition and model evaluation and facilitate deep learning applications in genomics.

• Wolfgang Kopp
• Altuna Akalin

Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues

Tissue clearing has revolutionised histology, but limited penetration of antibodies and stains into thick tissue segments is still a bottleneck. Here, the authors characterise optically cleared tissue as an electrolyte gel and apply this knowledge to stain the entirety of thick tissue samples.

• Etsuo A. Susaki
• Chika Shimizu
• Hiroki R. Ueda

Sestrins are evolutionarily conserved mediators of exercise benefits

Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.

• Myungjin Kim
• Alyson Sujkowski
• Jun Hee Lee

Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers

Fasting diets are emerging as an approach to delay tumor progression and improve cancer therapies. Here, the authors show that the combination of fasting-mimicking diet with vitamin C decreases tumor development and increases chemotherapy efficacy in KRAS-mutant cancer.

• Maira Di Tano
• Franca Raucci
• Valter D. Longo

Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.

• Nayoung Kim
• Hong Kwan Kim
• Hae-Ock Lee

A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

• Gurnit Atwal
• PCAWG Consortium

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression

Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

• Anna S. E. Cuomo
• Daniel D. Seaton
• Oliver Stegle

Trajectory-based differential expression analysis for single-cell sequencing data

Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models.

• Koen Van den Berge
• Hector Roux de Bézieux
• Lieven Clement

Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome

Here, Pasolli et al. perform a large-scale genome-wide comparative analysis of publicly available and newly sequenced food and human metagenomes to investigate the prevalence and diversity of lactic acid bacteria (LAB), indicating food as a major source of LAB species in the human gut.

• Edoardo Pasolli
• Francesca De Filippis
• Danilo Ercolini

Genetic history from the Middle Neolithic to present on the Mediterranean island of Sardinia

Ancient DNA analysis of early European farmers has found a high level of genetic affinity with present-day Sardinians. Here, the authors generate genome-wide capture data for 70 individuals from Sardinia spanning the Middle Neolithic to Medieval period to reveal relationships with mainland European populations shifting over time.

• Joseph H. Marcus
• Cosimo Posth
• John Novembre

Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome

Sex and the APOE ε4 genotype are important risk factors for late-onset Alzheimer’s disease. In the current study, the authors investigate how sex and APOE ε4 genotype modify the association between Alzheimer’s disease biomarkers and metabolites in serum.

• Matthias Arnold
• Kwangsik Nho
• Gabi Kastenmüller

Integrative pathway enrichment analysis of multivariate omics data

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

• Marta Paczkowska
• Jonathan Barenboim

Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice

Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

• Stephanie J. Alexopoulos
• Sing-Young Chen
• Kyle L. Hoehn

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution

Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects.

• Yann W. Yap
• Patricia M. Rusu
• Adam J. Rose

Multiplexed CRISPR technologies for gene editing and transcriptional regulation

Multiplexed CRISPR technologies have recently emerged as powerful approaches for genetic editing and transcriptional regulation. Here the authors review this emerging technology and discuss challenges and considerations for future studies.

• Nicholas S. McCarty
• Alicia E. Graham
• Rodrigo Ledesma-Amaro

Determining sequencing depth in a single-cell RNA-seq experiment

For single-cell RNA-seq experiments the sequencing budget is limited, and how it should be optimally allocated to maximize information is not clear. Here the authors develop a mathematical framework to show that, for estimating many gene properties, the optimal allocation is to sequence at the depth of one read per cell per gene.

• Martin Jinye Zhang
• Vasilis Ntranos

Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels

Ceramides are a type of sphingolipid (SL) that have been shown to play a role in several metabolic disorders. Here, the authors investigate the effect of SL-production by gut Bacteroides on host SL homeostasis and show that microbiome-derived SLs enter host circulation and alter ceramide production.

• Elizabeth L. Johnson
• Stacey L. Heaver
• Ruth E. Ley

Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland

European populations underwent strong genetic changes during the Neolithic. Here, Furtwängler et al. provide ancient nuclear and mitochondrial genomic data from the region of Switzerland during the end of the Neolithic and the Early Bronze Age that reveal a complex genetic turnover during the arrival of steppe ancestry.

• Anja Furtwängler
• A. B. Rohrlach
• Johannes Krause

Brain insulin sensitivity is linked to adiposity and body fat distribution

Brain insulin action regulates eating behavior and whole-body energy fluxes, however the impact of brain insulin resistance on long-term weight and body fat composition is unknown. Here, the authors show that high brain insulin sensitivity is linked to weight loss during lifestyle intervention and associates with a favorable body fat distribution.

• Stephanie Kullmann
• Vera Valenta
• Martin Heni

Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair

Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

• Filipa C. Simões
• Thomas J. Cahill
• Paul R. Riley

Sexual-dimorphism in human immune system aging

Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

• Eladio J. Márquez
• Cheng-han Chung

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

• Tatsuya Tsukui
• Kai-Hui Sun
• Dean Sheppard

Pathway and network analysis of more than 2500 whole cancer genomes

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

• Matthew A. Reyna

Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4 + T cells to cytokines

Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an ‘effectorness gradient’ is depicted by a transcriptional continuum, which shapes the downstream genetic programs.

• Eddie Cano-Gamez
• Blagoje Soskic
• Gosia Trynka

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