The researchers found that Mic-628 works by attaching to CRY1, a protein that normally suppresses clock gene activity. This interaction encourages the formation of a larger molecular complex known as CLOCK-BMAL1-CRY1-Mic-628. Once formed, this complex switches on Per1 by acting at a specific DNA site called a “dual E-box.” Through this mechanism, Mic-628 shifts the timing of both the brain’s master clock located in the suprachiasmatic nucleus (SCN) and clocks in other organs, including the lungs. Notably, these clock shifts occurred together and did not depend on when the compound was given.

Faster Recovery From Jet Lag in Animal Tests

To test real-world relevance, the team used a mouse model designed to mimic jet lag by advancing the light-dark cycle by six hours (6-hour light-dark phase advance). Mice that received a single oral dose of Mic-628 adjusted to the new schedule much faster, taking four days instead of seven. Further mathematical analysis showed that this steady, one-direction shift forward is driven by a built-in feedback loop involving the PER1 protein, which helps stabilize the clock change.

Why Advancing the Clock Is So Difficult

Adjusting to earlier schedules, such as traveling east across time zones or working night shifts, requires the body clock to move forward. This type of adjustment is typically slower and more stressful for the body than delaying the clock. Common approaches like light exposure or melatonin depend heavily on precise timing and often produce uneven results. Because Mic-628 consistently advances the clock regardless of dosing time, it offers a fundamentally different drug-based approach to circadian reset.

What Comes Next for Mic-628

The researchers plan to continue studying Mic-628 to better understand its safety and effectiveness in additional animal studies and in humans. Since the compound reliably moves the body clock forward through a clearly defined biological pathway, it could become a model “smart drug” for addressing jet lag, sleep problems linked to shift work, and other disorders caused by circadian misalignment.

The findings were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The compound studied is called indole. It is produced by beneficial gut bacteria when they break down tryptophan, an amino acid found in foods like turkey and nuts. The results add to growing research focused on preventing metabolic dysfunction-associated steatotic liver disease (MASLD). This form of fatty liver disease affects both adults and children, but it often advances more quickly in children and is closely linked to diabetes.

“The prevalence of MASLD in children is about 30% in those with obesity and about 10% in children without obesity,” said Jed Friedman, Ph.D., director of the OU Health Harold Hamm Diabetes Center and professor of biochemistry and physiology in the OU College of Medicine. “Unfortunately, the risk is higher if a mother is obese or consumes a poor diet. The disease in children is silent and typically isn’t discovered until a parent seeks help for their child for liver-related symptoms.”

Testing the Role of the Microbiome

Friedman led the study alongside Karen Jonscher, Ph.D., associate professor of biochemistry and physiology in the OU College of Medicine. Their work was published in the journal eBioMedicine. The team set out to explore whether gut bacteria, known together as the microbiome, influence how fatty liver disease develops.

To investigate this, female mice were fed a high-fat, high-sugar (Western-style) diet throughout pregnancy and lactation. Some of the mice also received indole. After they were weaned, the offspring were placed on a standard diet and later switched to a Western-style diet to encourage the development of fatty liver disease.

“Because offspring inherit their microbiome from their mother, a poor maternal diet can shape the infant’s microbiome in harmful ways,” Friedman said.

Healthier Livers and Lasting Benefits

Offspring born to mothers that received indole showed multiple health advantages. They had healthier livers, gained less weight, maintained lower blood sugar levels, and developed smaller fat cells, even after being exposed to an unhealthy diet later in life. The researchers also observed activation of a protective gut pathway involving the acyl hydrocarbon receptor (AHR).

The study found no increase in harmful liver fats known as long-chain ceramides, while levels of beneficial very long-chain ceramides rose. In a key experiment, gut bacteria from the protected offspring were transferred to other mice that had not received indole. Those mice also experienced less liver damage, reinforcing the idea that the microbiome itself plays a central protective role.

Implications for Preventing Childhood MASLD

Although the research was conducted in animals and cannot yet be applied directly to humans, the findings point to new strategies for reducing the growing impact of MASLD through early prevention.

At present, weight loss is the only effective treatment option for pediatric MASLD once the disease is established, and there are no approved medications. “Anything we can do to improve the mother’s microbiome may help prevent the development of MASLD in the offspring,” Jonscher said. “That would be far better than trying to reverse the disease once it has already progressed.”

The study focuses on three major groups of calcifying plankton: coccolithophores, foraminifers, and pteropods. According to the authors, climate models often simplify or exclude these organisms, which can lead to an incomplete picture of how the ocean responds to climate change.

How Calcifying Plankton Shape the Carbon Cycle

When climate models leave out calcifying plankton, they may miss key steps in the global carbon cycle. These organisms build tiny shells made of calcium carbonate (CaCO₃), a substance that plays a central role in ocean chemistry. As plankton grow and die, they help move carbon from the atmosphere into deeper layers of the ocean.

This process, known as the ocean carbon pump, helps stabilize Earth’s climate over long periods of time. It also affects seawater chemistry and contributes to the formation of sediments that scientists use to study past climates.

“Plankton shells are tiny, but together they shape the chemistry of our oceans and the climate of our planet,” said Patrizia Ziveri, ICREA research professor at ICTA-UAB and lead author of the study. “By leaving them out of climate models, we risk overlooking fundamental processes that determine how the Earth system responds to climate change.”

The Missing Process of Shallow Dissolution

The researchers point out that much of the calcium carbonate produced by plankton does not sink all the way to the ocean floor. Instead, a significant portion dissolves in the upper ocean, a process known as “shallow dissolution.” This breakdown is driven by biological activity, including predation, clumping of particles, and microbial respiration.

Shallow dissolution changes ocean chemistry in important ways, yet it is largely missing from major Earth System Models (e.g. CMIP6) used in global climate assessments. Without accounting for this process, models may misjudge how carbon moves through the ocean and how the system responds to environmental stress.

Different Plankton Face Different Climate Threats

The study also emphasizes that not all calcifying plankton behave the same way. Each group has unique characteristics that influence where it lives, how it functions in marine ecosystems, and how vulnerable it is to climate change.

Coccolithophores are the largest producers of CaCO₃, but they are especially sensitive to ocean acidification because they lack specialized mechanisms to remove excess acidity from their cells. Foraminifers and pteropods do have such mechanisms, but they face other risks, including declining oxygen levels and rising ocean temperatures. Together, these organisms determine how carbon is stored and recycled in the ocean, and treating them as a single group can oversimplify the ocean’s response to climate pressures.

Improving Climate Models With Better Ocean Biology

The authors call for urgent efforts to measure how much calcium carbonate each plankton group produces, dissolves, and exports to deeper waters. They argue that incorporating these details into climate models would improve predictions of ocean and atmosphere interactions, long-term carbon storage, and the interpretation of sediment records used to reconstruct Earth’s climate history.

“If we ignore the ocean’s smallest organisms, we might miss important climate dynamics,” says Dr. Ziveri. “Integrating calcifying plankton into climate models could offer sharper predictions and deeper insights into how ecosystems and societies may be affected.”

The researchers conclude that closing these knowledge gaps is essential for building the next generation of climate models, ones that more accurately reflect the biological complexity of the oceans.

Both outbreaks had major consequences in the United States. The 2009 H1N1 flu pandemic led to 274,304 hospitalizations and 12,469 deaths. The COVID-19 pandemic has been even more devastating, with 1.2 million confirmed deaths reported so far.

Modeling the Spread Across Cities

The researchers aimed to understand how these pandemics traveled geographically in order to improve planning for future outbreaks. To do this, they combined detailed information about how each virus spreads with computer models that accounted for air travel, everyday commuting, and the possibility of superspreading events. Their analysis focused on more than three hundred metropolitan areas across the U.S.

Rapid Expansion Before Early Warnings

The simulations revealed that both pandemics were already circulating widely in most metro areas within just a few weeks. This widespread transmission often occurred before early case detection or government response measures were in place. Although H1N1 and COVID-19 followed different routes between locations, both relied on shared transmission hubs, including major metro areas such as New York and Atlanta. Air travel played a much larger role than commuting in driving this rapid spread. At the same time, unpredictable transmission patterns added significant uncertainty, making it difficult to anticipate where outbreaks would emerge in real time.

“The rapid and uncertain spread of the 2009 H1N1 flu and 2020 COVID-19 pandemics underscores the challenges for timely detection and control. Expanding wastewater surveillance coverage coupled with effective infection control could potentially slow the initial spread of future pandemics,” says the study’s senior author, Sen Pei, PhD, assistant professor of environmental health sciences at Columbia Mailman School.

Wastewater Surveillance and Pandemic Preparedness

Previous research has highlighted the value of wastewater surveillance as an early warning tool. This new study adds further support, showing that expanding wastewater monitoring could play an important role in improving pandemic preparedness and slowing early transmission.

Lessons Beyond H1N1 and COVID-19

In addition to reconstructing the spread of the last two pandemics, the researchers developed a flexible framework that can be used to study the early stages of other outbreaks. While human movement, especially air travel, is a major driver of pandemic spread, the team notes that other factors also influence how outbreaks unfold. These include population demographics, school calendars, winter holidays, and weather patterns.

The study’s first author is Renquan Zhang, Dalian University of Technology, Dalian, China. Additional authors include Rui Deng and Sitong Liu from Dalian University of Technology; Qing Yao and Jeffrey Shaman from Columbia University; Bryan T. Grenfell from Princeton; and Cécile Viboud from the National Institutes of Health.

For more than ten years, Jeffrey Shaman and colleagues, including Sen Pei, have worked to improve methods for tracking and simulating the spread of infectious diseases such as influenza and COVID-19. Their real-time forecasting tools estimate how quickly outbreaks grow, where they are likely to spread, and when they may peak, helping guide public health decision-making.

The study, published in Psychological Medicine, also examined the effects of hormone replacement therapy (HRT). While HRT did not appear to prevent these brain or mental health changes, it was associated with a slower decline in reaction speed.

Understanding Menopause and Its Symptoms

Menopause marks the stage of life when a woman’s menstrual periods permanently stop due to declining hormone levels. It most commonly occurs between ages 45 and 55 and is often accompanied by symptoms such as hot flushes, low mood, and disrupted sleep. Previous research has also linked menopause to changes in cognitive abilities, including memory, attention, and language.

To help manage menopause related symptoms, particularly depression and sleep problems, many women are prescribed HRT. In England, 15% of women were prescribed HRT in 2023. Despite its widespread use, scientists still have limited insight into how menopause and HRT affect the brain, thinking skills, and mental health.

A Large Study Using UK Biobank Data

To better understand these effects, researchers analyzed data from the UK Biobank involving nearly 125,000 women. Participants were divided into three groups: women who had not yet reached menopause, women who were post-menopause and had never used HRT, and women who were post-menopause and had used HRT.

Participants completed questionnaires about menopause symptoms, mental health, sleep patterns, and overall health. Some also completed cognitive tests measuring memory and reaction time. In addition, around 11,000 women underwent magnetic resonance imaging (MRI) scans, which allowed researchers to examine differences in brain structure.

The average age at menopause among participants was about 49.5 years. Women who were prescribed HRT typically began treatment at around age 49.

Anxiety Depression and Sleep After Menopause

Women who had gone through menopause were more likely than those who had not to seek help from a GP or psychiatrist for anxiety, nervousness, or depression. They also scored higher on depression questionnaires and were more likely to have been prescribed antidepressant medications.

Women in the HRT group showed higher levels of anxiety and depression compared with women who did not use HRT. However, further analysis revealed that these differences were already present before menopause began. According to the researchers, this suggests that some GPs may have prescribed HRT in anticipation that menopause could worsen existing symptoms.

Sleep problems were also more common after menopause. Post-menopausal women were more likely to report insomnia, reduced sleep, and ongoing tiredness. Women using HRT reported feeling the most fatigued of all three groups, even though their total sleep duration did not differ from post-menopausal women who were not taking HRT.

The Importance of Lifestyle and Mental Health Support

Dr. Christelle Langley from the Department of Psychiatry said: “Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not. A healthy lifestyle — exercising, keeping active and eating a healthy diet, for example — is particularly important during this period to help mitigate some of its effects.

“We all need to be more sensitive to not only the physical, but also the mental health of women during menopause, however, and recognize when they are struggling. There should be no embarrassment in letting others know what you’re going through and asking for help.”

Reaction Time Slows While Memory Remains Stable

Menopause was also linked to changes in cognitive performance. Women who were post-menopause and not using HRT showed slower reaction times compared with women who had not yet reached menopause and those who were using HRT. Memory performance did not differ significantly among the three groups.

Dr. Katharina Zühlsdorff from the Department of Psychology at the University of Cambridge, said: “As we age, our reaction times tend to get slower — it’s just a part of the natural ageing process and it happens to both women and men. You can imagine being asked a question at a quiz — while you might still arrive at the correct answer as your younger self, younger people would no doubt get there much faster. Menopause seems to accelerate this process, but HRT appears to put the brakes on, slowing the ageing process slightly.”

Grey Matter Loss in Brain Regions Linked to Memory and Emotion

Brain imaging revealed that women who were post-menopause showed significant reductions in grey matter volume, regardless of whether they had used HRT. Grey matter contains nerve cell bodies and plays a key role in processing information, controlling movement, and supporting memory and emotional regulation.

The most affected areas included the hippocampus (responsible for forming and storing memories), the entorhinal cortex (the ‘gateway’ for passing information between the hippocampus and the rest of the brain), and the anterior cingulate cortex (part of the brain that helps you manage emotions, make decisions, and focus your attention).

Possible Clues to Dementia Risk in Women

Professor Barbara Sahakian, the study’s senior author from the Department of Psychiatry, added: “The brain regions where we saw these differences are ones that tend to be affected by Alzheimer’s disease. Menopause could make these women vulnerable further down the line. While not the whole story, it may help explain why we see almost twice as many cases of dementia in women than in men.”

The evidence for that change can still be found today.

It is embedded in human hair.

Hair Samples Trace Lead Exposure Back to 1916

Scientists at the University of Utah analyzed hair samples and discovered steep declines in lead levels going back more than a century. Their results show a clear downward trend beginning after environmental regulations were introduced.

“We were able to show through our hair samples what the lead concentrations are before and after the establishment of regulations by the EPA,” said demographer Ken Smith, a distinguished professor emeritus of family and consumer studies. “We have hair samples spanning about 100 years. And back when the regulations were absent, the lead levels were about 100 times higher than they are after the regulations.”

A Metal That Was Useful and Dangerous

The study, published in PNAS, highlights how environmental protections have shaped public health outcomes. It also points out that some lead regulations are now being weakened by the Trump administration as part of a broader effort to loosen environmental safeguards.

“We should not forget the lessons of history. And the lesson is those regulations have been very important,” said co-author Thure Cerling, a distinguished professor of both geology and biology. “Sometimes they seem onerous and mean that industry can’t do exactly what they’d like to do when they want to do it or as quickly as they want to do it. But it’s had really, really positive effects.”

Lead is the heaviest of the heavy metals and, like mercury and arsenic, it accumulates in living tissue and is harmful even at low concentrations. Despite these risks, it was widely used for decades because of its practical advantages. Lead was commonly used in pipes and added to paint to improve durability, speed drying, and create brighter colors. It was also blended into gasoline to improve engine performance by preventing pistons from “knocking.”

By the 1970s, the health dangers were well established, prompting the EPA to begin removing lead from paint, plumbing materials, gasoline, and other consumer products.

How Family Keepsakes Became Scientific Evidence

To find out whether these policy changes truly reduced lead exposure in people, Smith worked with geologist Diego Fernandez and Cerling. Fernandez and Cerling had developed methods to determine where animals lived and what they ate by analyzing the chemistry of hair and teeth.

The lead study grew out of earlier research funded by the university’s Center on Aging and the National Institutes of Health. That earlier work involved Utah residents who agreed to provide blood samples along with detailed family health information.

For the new research, participants were asked to submit hair samples from adulthood and from earlier in life. Some went a step further, locating hair preserved in family scrapbooks that dated back as much as a century. Altogether, the team collected hair from 48 individuals, creating a valuable record of lead exposure along Utah’s Wasatch Front, an area that once faced heavy industrial pollution.

“The Utah part of this is so interesting because of the way people keep track of their family history. I don’t know that you could do this in New York or Florida,” said Smith, who led the U’s Pedigree and Population Program at the Huntsman Cancer Center while the studies were underway.

Much of this region supported a major smelting industry throughout the 20th century, particularly in Midvale and Murray. Most of Utah’s smelters closed by the 1970s, around the same time the EPA began enforcing stricter limits on lead use.

Why Hair Preserves Lead So Well

The researchers analyzed the samples using mass spectrometry equipment at a facility overseen by Fernandez.

“The surface of the hair is special. We can tell that some elements get concentrated and accumulated in the surface. Lead is one of those. That makes it easier because lead is not lost over time,” said Fernandez, a research professor in the Department of Geology & Geophysics. “Because mass spectrometry is very sensitive, we can do it with one hair strand, though we cannot tell where the lead is in the hair. It’s probably in the surface mostly, but it could be also coming from the blood if that hair was synthesized when there was high lead in the blood.”

While blood tests offer a more precise snapshot of exposure at a specific moment, hair is far easier to collect and preserve. More importantly, it provides insight into past exposure for people who are now older or no longer alive.

“It doesn’t really record that internal blood concentration that your brain is seeing, but it tells you about that overall environmental exposure,” Cerling said. “One of the things that we found is that hair records that original value, but then the longer the hair has been exposed to the environment, the higher the lead concentrations are.”

Leaded Gasoline Left a Clear Chemical Record

The decline in lead found in hair closely mirrors the reduction of lead in gasoline after the EPA was created under President Richard Nixon.

Before 1970, gasoline typically contained about 2 grams of lead per gallon. Although that amount may seem small, the scale of fuel consumption made it significant. With billions of gallons burned each year, this resulted in nearly 2 pounds of lead entering the environment per person annually.

“It’s an enormous amount of lead that’s being put into the environment and quite locally,” Cerling said. “It’s just coming out of the tailpipe, goes up in the air and then it comes down. It’s in the air for a number of days, especially during the inversions that we have and it absorbs into your hair, you breathe it and it goes into your lungs.”

After the 1970s, even as gasoline use continued to rise in the United States, lead levels measured in hair fell sharply. Concentrations dropped from as high as 100 parts per million (ppm) to about 10 ppm by 1990. By 2024, average levels had fallen to less than 1 ppm.

The study, titled “Lead in archived hair documents decline in human lead (Pb) exposure since establishment of the US Environmental Protection Agency,” was published in PNAS, or Proceedings of the National Academy of Sciences. Support came from the Huntsman Cancer Foundation and the National Cancer Institute through a grant to the Utah Population Database and the University of Utah.