At the start of the 20th century, northern elephant seals were on the brink of being wiped out by hunting. ‘Genetic analyses suggest that the population was likely reduced to fewer than 25 animals at that time,’ explains Professor Dr Joseph Hoffman, lead author of the study and head of the Evolutionary Population Genetics group at Bielefeld University. Such drastic population declines can squeeze out a species’ genetic diversity, increasing the risk of inbreeding and threatening its survival. The population of northern elephant seals has since recovered to around 225,000 individuals. The study published in the journal ‘Nature Ecology and Evolution’ examines how this near-extinction event impacted the species’ genetic diversity and health.

Adaptability at risk

For their analyses, the researchers combined genetic data, health records, modelling of population sizes and genetic simulations. Their findings suggest that the severe population decline led to the loss of many beneficial and harmful genes from the northern elephant seal’s gene pool. This pattern was not observed in the closely related southern elephant seal, which did not experience such a drastic decline.

‘The highly reduced genetic diversity, including the loss of beneficial gene copies, may impair the ability of northern elephant seals to cope with future environmental changes, including those caused by anthropogenic climate change, changes to the species’ habitat, or even natural threats such as disease outbreaks,’ warns Professor Dr Kanchon K. Dasmahapatra from the University of York, UK, who is the senior author of the study.

Surprising results on inbreeding

All individuals of a species carry some harmful mutations, though their effects are usually hidden. However, inbred individuals may face health issues as these mutations become exposed. ‘We looked at several key health traits in these seals, including body weight, blubber thickness and disease susceptibility. To our surprise, we found no signs of health problems related to inbreeding,’ Joseph Hoffman says. ‘We believe the severe population decline may have eliminated many harmful mutations.’

Significance for species conservation

‘Our study illustrates how a species’ unique population history shapes its genetic diversity,’ says Dasmahapatra. The findings offer important insights for species conservation and ecosystem management. Hoffman adds: ‘Our research underscores the importance of understanding a species’ history when planning conservation strategies. Each species responds differently to threats, so individualized approaches are essential.’

A team of researchers led by University of Maryland Atmospheric and Oceanic Science Professor Ning Zeng analyzed a 3,775-year-old log and the soil it was excavated from. Their analysis, published on September 27, 2024, revealed that the log had lost less than 5% carbon dioxide from its original state thanks to the low-permeability clay soil that covered it.

“The wood is nice and solid — you could probably make a piece of furniture out of it,” Zeng noted.

Understanding the unique environmental factors that kept that ancient log in mint condition could help researchers perfect an emerging climate solution known as “wood vaulting,” which involves taking wood that is not commercially viable — such as trees destroyed by disease or wildfires, old furniture or unused construction materials — and burying it to stop its decomposition.

Trees naturally sequester carbon dioxide — a potent planet-warming gas — for as long as they live, making tree-planting projects a popular method of mitigating climate change. But on the flip side, when trees die and decompose, that greenhouse gas is released back into the atmosphere, contributing to global warming.

“People tend to think, ‘Who doesn’t know how to dig a hole and bury some wood?'” Zeng said. “But think about how many wooden coffins were buried in human history. How many of them survived? For a timescale of hundreds or thousands of years, we need the right conditions.”

In 2013, while conducting a wood vaulting pilot project in Quebec, Canada, Zeng discovered the 3,775-year-old log that became the focus of the Science study — a chance encounter that for Zeng felt “kind of miraculous.” While digging a trench to bury fresh wood, Zeng and other researchers spotted the log about 6.5 feet below the surface.

“When the excavator pulled a log out of the ground and threw it over to us, the three ecologists that I had invited from McGill University immediately identified it as Eastern red cedar,” Zeng recalled. “You could tell how well it was preserved. I remember standing there thinking, ‘Wow, here’s the evidence that we need!'”

While past studies have analyzed old samples of preserved wood, they tended to overlook the surrounding soil conditions, according to Zeng.

“There is a lot of geological and archeological evidence of preserved wood from hundreds to millions of years ago, but the focus of those studies was not ‘How we can engineer a wood vault to preserve that wood?'” Zeng said. “And the problem with designing a new experiment is that we can’t wait 100 years for the results.”

Shortly after the Quebec dig, UMD’s collaborators at MAPAQ, a government ministry in Montreal, conducted carbon dating to determine the log’s age. Then, in 2021, Distinguished University Professor Liangbing Hu in UMD’s Department of Materials Science and Engineering helped Zeng analyze the 3,775-year-old sample’s microscopic structure, chemical composition, mechanical strength and density. They then compared those results to that of a freshly cut Eastern red cedar log, which revealed that the older sample had lost very little carbon dioxide.

The type of soil covering the log was the key reason for its remarkable preservation. The clay soil in that part of Quebec had an especially low permeability, meaning that it prevented or drastically slowed oxygen from reaching the log while also keeping out fungi and insects, the decomposers typically found in soil.

Because clay soil is common, wood vaulting could become a viable and low-cost option in many parts of the world. As a climate solution, Zeng noted that wood vaulting is best paired with other tactics to slow global warming, including reducing greenhouse gas emissions.

As he and his colleagues continue to optimize wood vaulting, he looks forward to putting what they’ve learned into practice to help curb climate change.

“It’s quite an exciting discovery,” Zeng said of this latest study. “The urgency of climate change has become such a prominent issue, so there was even more motivation to get this analysis going.”

They also showed that aspirin was able to improve hormone deficiency symptoms in mice with this condition.

People with mutations in a gene called Sox3 develop hypopituitarism, where the pituitary gland doesn’t make enough hormones. It can result in growth problems, infertility and poor responses of the body to stress.

In research published today in PLOS Genetics, the scientists at the Crick removed Sox3 from mice, causing them to develop hypopituitarism around the time of weaning (starting to eat solid food).

They found that mutations in Sox3 largely affect the hypothalamus in the brain, which instructs the pituitary gland to release hormones. However, the gene is normally active in several brain cell types, so the first task was to ask which specific cells were most affected by its absence.

The scientists observed a reduced number of cells called NG2 glia, suggesting that these play a critical role in inducing the pituitary gland cells to mature around weaning, which was not known previously. This could explain the associated impact on hormone production.

The team then treated the mice with a low dose of aspirin for 21 days. This caused the number of NG2 glia in the hypothalamus to increase and reversed the symptoms of hypopituitarism in the mice.

Although it’s not yet clear how aspirin had this effect, the findings suggest that it could be explored as a potential treatment for people with Sox3 mutations or other situations where the NG2 glia are compromised.

An incidental discovery revealed the role of gut bacteria in hormone production

When the National Institute for Medical Research (NIMR) merged with the Crick in 2015, mouse embryos were transferred from the former building to the latter, and this included the mice with Sox3 mutations.

When these mice reached the weaning stage at the Crick, the researchers were surprised to find that they no longer had the expected hormonal deficiencies.

After exploring a number of possible causes, lead author Christophe Galichet compared the microbiome — bacteria, fungi and viruses that live in the gut — in the mice from the Crick and mice from the NIMR, observing several differences in its makeup and diversity. This could have been due to the change in diet, water environment, or other factors that accompanied the relocation.

He also examined the number of NG2 glia in the Crick mice, finding that these were also at normal levels, suggesting that the Crick-fed microbiome was somehow protective against hypopituitarism.

To confirm this theory, Christophe transplanted faecal matter retained from NIMR mice into Crick mice, observing that the Crick mice once again showed symptoms of hypopituitarism and had lower numbers of NG2 glia.

Although the exact mechanism is unknown, the scientists conclude that the make-up of the gut microbiome is an example of an important environmental factor having a significant influence on the consequences of a genetic mutation, in this case influencing the function of the hypothalamus and pituitary gland.

Christophe Galichet, former Senior Laboratory Research Scientist at the Crick and now Research Operations Manager at the Sainsbury Wellcome Centre, said: “It was a huge surprise to find that changes in the gut microbiome reversed hypopituitarism in the mice without Sox3. It’s reinforced to me how important it is to be aware of all variable factors, including the microbiome, when working with animals in research and how nurture can influence nature.”

Robin Lovell-Badge, Group Leader of the Stem Cell Biology and Developmental Genetics Laboratory at the Crick, said: “Hypopituitarism can result from trauma as well as rare mutations, and it can have some profound effects on health in general. As well as suggesting potential options for treatment, our work reinforces how important the gut-brain link is. The next step for this research will be to work out exactly how aspirin and the microbiome influence NG2 glia, and then study this effect in people so we can see if these relatively accessible interventions could help treat hypopituitarism.”

They published their findings today (Sept. 26) in JAMA Network Open.

“The cause of SUID is believed to be multi-factorial. Even with education about safe sleep environments and the back-to-sleep campaign encouraging parents to put babies to sleep on their backs, there’s still a high rate of SUID,” said Emma Guare, a fourth-year medical student at Penn State College of Medicine and first author of the paper. “It’s been hypothesized that there might be a link between infection and SUID and we wanted to better understand that connection, particularly as endemic infection rates shifted during the pandemic.”

In 2022, approximately 3,700 infants died unexpectedly in the United States, according to the Centers for Disease Control and Prevention (CDC). SUID is an umbrella term for unexpected death of an infant under the age of one year from known and unknown causes. SIDS is a type of SUID that occurs during sleep and where the cause of death is not known, even after a full investigation, and accounts for roughly one-third of SUID cases.

The research team examined the rate of both SUID and SIDS during the COVID-19 pandemic and compared it to the immediate period prior to the pandemic. Between March 1, 2018, and Dec. 31, 2021, there were 14,308 cases of SUID, based on national data on mortality provided by the CDC.

The research team found that the risk of SUID and SIDS increased during the pandemic when they compared monthly cases to the pre-pandemic period. The greatest increase was observed in 2021 when rates for SUID and SIDS increased 9% and 10%, respectively, compared to the pre-pandemic period. There was a notable shift in SUID rates from June to December 2021, when the monthly rate of SUID increased between 10% and 14% compared to pre-pandemic levels.

Measures put in place to mitigate the pandemic also interrupted the spread of respiratory illnesses like RSV, keeping rates low during 2020. However, as these measures were lifted during the second year of the pandemic, seasonal respiratory viruses began to circulate more widely at unexpected times and with more intensity.

While there were few RSV-related hospitalizations in 2020, cases surged between June and December 2021, an “off-season” for RSV, which typically is active between October and April. This seasonal shift in RSV closely mirrored the monthly changes in SUID that were observed in 2021.

“We don’t know what makes babies who die from SUID or SIDS more vulnerable, whether it’s genetics or something else. It could be that infections like RSV amplify those factors and make them more vulnerable,” said co-author Erich Batra, associate professor of pediatrics and family and community medicine at Penn State College of Medicine. “With RSV in particular, there have been questions about whether RSV causes more apnea, when you stop breathing temporarily, than other viruses and if that contributes to an environment conducive to SUID.”

The team noted that further research is needed to better understand the role of infection in SUID and SIDS and whether infections like RSV may contribute to a portion of SUID and SIDS cases.

“Practicing safe sleep practices is just as important, if not more important when babies are sick,” Batra said. He encouraged caregivers to continue to place babies to sleep on their backs, avoid soft bedding and not share a bed.

Other Penn State College of Medicine authors on the paper include Catharine Paules, associate professor of medicine; Vernon Chinchilli, Distinguished Professor of Public Health Sciences; Paddy Ssentongo, assistant professor of public health sciences; and Rong Zhao, doctoral student in biostatistics.

A team led by scientists at UC Riverside, UC Irvine, and Yale School of Medicine has now designed a new drug against malaria and identified its mechanism of action. The researchers found the drug, called MED6-189, is effective against drug-sensitive and drug-resistant P. falciparum strains in vitro as well as in a humanized mouse model (the mice were engineered to have human blood).

The researchers report in the journal Science this week that MED6-189 works by targeting and disrupting not only the apicoplast, an organelle found in P. falciparum cells, but also the vesicular trafficking pathways. They found that this dual mode of action prevents the pathogen from developing resistance, making the drug a highly effective antimalarial compound and a promising new lead in the fight against malaria.

“Disruption of the apicoplast and vesicular trafficking blocks the parasite’s development and thus eliminates infection in red blood cells and in our humanized mouse model of P. falciparum malaria,” said Karine Le Roch, a professor of molecular, cell and systems biology at UCR and the paper’s senior author. “We found MED6-189 was also potent against other zoonotic Plasmodium parasites, such as P. knowlesi and P. cynomolgi.“

MED6-189 is a synthetic compound inspired by a compound extracted from marine sponges. The lab of Christopher Vanderwal, a professor of chemistry and pharmaceutical sciences at UC Irvine, synthesized the compound.

“Many of the best antimalarial agents are natural products, or are derived from them,” he said. “For example, artemisinin, initially isolated from the sweet wormwood plant, and analogues thereof, are critically important for treatment of malaria. MED6-189 is a close relative of a different class of natural products, called isocyanoterpenes, that seem to target multiple pathways in P. falciparum. That is beneficial because had only one pathway been targeted, the parasite could develop resistance to the compound more quickly.”

When researchers at GSK, a pharmaceutical company in Spain, administered MED6-189 to the mice infected with P. falciparum, they found it cleared the mice of the parasite. In collaboration with Choukri Ben Mamoun, a professor of medicine and microbial pathogenesis at the Yale School of Medicine, the team also tested the compound against P. knowlesi, a parasite that infects monkeys, and found it worked as intended, clearing the monkey’s parasite-infected red blood cells.

Next, the team plans to continue the optimization of MED6-189 and further confirm the modified compound’s mechanisms of action using a systems biology approach. Systems biology is a biomedical research approach to understanding the larger picture of a biological system. It offers researchers a way to examine how different living organisms and cells interact at larger scales.

Le Roch, Vanderwal, and Ben Mamoun were joined in the research by fellow scientists at the Stowers Institute for Medical Research in Kansas City, Missouri; GSK; and the University of Georgia.

The research was supported by a grant to Le Roch, Vanderwal, and Ben Mamoun and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. At UCR, Le Roch directs the Center for Infectious Disease and Vector Research.

The title of the research paper is “A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in P. falciparum Malaria.”

As one of the world’s most densely population cities, Dhaka deals with a high burden of diarrheal diseases. While some studies have looked at how weather affects diarrhea in Bangladesh, few have examined the future impact of climate change. A warmer climate is expected to worsen this public health issue by making the city hotter and exacerbating water quality issues.

In the new study, researchers estimated the risks posed by diarrheal diseases under various global warming scenarios. They looked to see if daily rainfall, humidity and temperature in Dhaka affected rates of hospitalizations from diarrheal disease, using data from about 3 million diarrhea cases treated at a major hospital in Dhaka from 1981 to 2010. Statistical analysis revealed that higher daily temperatures significantly increased the risk of diarrhea for all age groups. Assuming that the planet warms by 1.5 °C to 2 °C on average, hospitalizations due to diarrheal disease are expected to increase by 4.5% to 7.4% in all age groups by the end of the century. Children under five may be especially hard hit, with hospitalization rates estiated to increase by 5.7% to 9.4%.

Under the Paris Agreement, an international treaty on climate change, countries agreed to set global warming targets to under 2°C. The new study shows that even if these targets are met, hospitalizations from diarrhea will increase substantially in Dhaka. These findings underscore the importance of better preparing the city to prevent and manage diarrheal diseases.

The authors add: “Diarrhoea hospitalisation will increase significantly in Dhaka by 4.5 — 7.4% in all age groups by the 2100s even if the global warming targets adopted by the Paris Agreement is reached. This underscores the importance of preparing the city for management and prevention of diarrhoeal diseases.”