Publisher Health

Scripps Research scientists have developed a machine-learning system — a type of artificial intelligence (AI) application — that can track the detailed evolution of epidemic viruses and predict the emergence of viral variants with important new properties.
In a paper in Cell Patterns on July 21, 2023, the scientists demonstrated the system by using data on recorded SARS-CoV-2 variants and COVID-19 mortality rates. They showed that the system could have predicted the emergence of new SARS-CoV-2 “variants of concern” (VOCs) ahead of their official designations by the World Health Organization (WHO). Their findings point to the possibility of using such a system in real-time to track future viral pandemics.
“There are rules of pandemic virus evolution that we have not understood but can be discovered, and used in an actionable sense by private and public health organizations, through this unprecedented machine-learning approach,” says study senior author William Balch, PhD, professor in the Department of Molecular Medicine at Scripps Research.
The co-first authors of the study were Salvatore Loguercio, PhD, a staff scientist in the Balch lab at the time of the study, and currently a staff scientist at the Scripps Research Translational Institute; and Ben Calverley, PhD, a postdoctoral research associate in the Balch lab.
The Balch lab specializes in the development of computational, often AI-based methods to illuminate how genetic variations alter the symptoms and spread of diseases. For this study, they applied their approach to the COVID-19 pandemic. They developed machine-learning software, using a strategy called Gaussian process-based spatial covariance, to relate three data sets spanning the course of the pandemic: the genetic sequences of SARS-CoV-2 variants found in infected people worldwide, the frequencies of those variants, and the global mortality rate for COVID-19.
“This computational method used data from publicly available repositories,” Loguercio says. “But it can be applied to any genetic mapping resource.”
The software enabled the researchers to track sets of genetic changes appearing in SARS-CoV-2 variants around the world. These changes — typically trending towards increased spread rates and decreased mortality rates — signified the virus’ adaptations to lockdowns, mask wearing, vaccines, increasing natural immunity in the global population, and the relentless competition among SARS-CoV-2 variants themselves.

Immune systems develop specific genes to combat common bacteria such as those found in food, new research shows.
Previous theories have suggested that antimicrobial peptides — a kind of natural antibiotics — have a general role in killing a range of bacteria.
However, the new study, published in Science, examined how the immune systems of fruit flies are shaped by the bacteria in their food and environment.
The researchers, from the Swiss Federal Institute of Technology and the University of Exeter, found two peptides that each control a single bacterial species commonly encountered by the flies.
“We know that an animal’s food and environment determine the bacteria it encounters,” said Dr Mark Hanson, from the Centre for Ecology and Conservation on Exeter’s Penryn Campus in Cornwall.
“This in turn shapes its ‘microbiome’ — the collection of microbes that live in and on its body — and our study shows how immune systems evolve in response to this, to control common bacteria that could otherwise cause harm.
“In immune terms, it proves the saying ‘you are what you eat’ — the flies’ immune systems contain peptides with remarkably specific functions for controlling common bacteria.”
One such bacterium — Acetobacter, found in the fruits that flies eat (and in fruits humans eat) — can harm flies if it escapes the gut and reaches the bloodstream.

Perhaps the most profound advance in primate evolution occurred about 6 million years ago when our ancestors started walking on two legs. The gradual shift to bipedal locomotion is thought to have made primates more adaptable to diverse environments and freed their hands to make use of tools, which in turn accelerated cognitive development. With those changes, the stage was set for modern humans.
The genetic changes that made possible the transition from knuckle-based scampering in great apes to upright walking in humans have now been uncovered in a new study by researchers at Columbia University and the University of Texas.
Using a combination of deep learning (a form of artificial intelligence) and genome-wide association studies, the researchers have created the first map of the genomic regions responsible for skeletal changes in primates that led to upright walking. The map reveals that genes that underlie the anatomical transitions observed in the fossil record were strongly acted on by natural selection and gave early humans an evolutionary advantage.
“On a more practical level, we’ve also identified genetic variants and skeletal features that are associated with hip, knee, and back arthritis, the leading causes of adult disability in the United States,” says Tarjinder Singh, PhD, assistant professor of computational and statistical genomics (in psychiatry) at the Columbia University Vagelos College of Physicians and Surgeons and a co-leader of the study.
For example, slight deviations from the average hip width-to-height ratio were associated with an increased risk of hip osteoarthritis, while slight deviations in the tibia-femur angle were associated with an increased risk of knee osteoarthritis. These insights could help researchers devise new ways to prevent and treat these debilitating conditions.
The findings were published July 21 in Science. The study was co-led by Vagheesh M. Narasimhan, PhD, assistant professor of integrative biology and of statistics and data sciences at the University of Texas at Austin.
New techniques deployed
The researchers applied deep learning to analyze more than 30,000 full-body X-rays from the UK Biobank. Deep learning, a technology modeled after the brain’s neural networks, trains computers to do what comes naturally to humans, such as driving a car or translating languages. In this case, the technique was used to standardize the X-rays, remove any images with quality issues, and then precisely measure dozens of skeletal features, tasks that would have taken the researchers months, if not years, to complete.

In Africa, climate change impacts are experienced as extreme events like drought and floods. Through the Famine Early Warning Systems Network (which leverages expertise from USG science agencies, universities, and the private sector) and the IGAD Climate Prediction and Applications Center, it has been possible to predict and monitor these climatic events, providing early warning of their impacts on agriculture to support humanitarian and resilience programming in the most food insecure countries of the world.
Science is beginning to catch up with and even get ahead of climate change. In a commentary for the journal Earth’s Future, UC Santa Barbara climate scientist Chris Funk and co-authors assert that predicting the droughts that cause severe food insecurity in the Eastern Horn of Africa (Kenya, Somalia and Ethiopia) is now possible, with months-long lead times that allow for measures to be taken that can help millions of the region’s farmers and pastoralists prepare for and adapt to the lean seasons.
“We’ve gotten very good at making these predictions,” said Funk, who directs UCSB’s Climate Hazards Center, a multidisciplinary alliance of scientists who work to predict droughts and food shortages in vulnerable areas.
In the summer of 2020, the CHC predicted that climate change, interacting with naturally occurring La Niña events, would bring devastating sequential drought to the Eastern Horn of Africa. The region normally has two wet seasons a year — spring and fall. An unprecedented five rainy seasons in a row failed. Eight months before each of those failures, the CHC anticipated droughts. Fortunately, agencies and other collaborators paid heed to those early warnings and were able to take effective actions, Funk said. Within the U.S. Agency for International Development (USAID), the forecasts helped motivate hundreds of millions of dollars in assistance for millions of starving people.
These efforts were a far cry from similar predictions of sequential droughts that the researchers, collaborating with the USAID-supported Famine Early Warning Systems Network, made for the same region ten years earlier. Predictions that went largely unheeded. “More than 250,000 Somalis died,” Funk said. “It was just really horrible.”
At the time, he said, the available forecasts weren’t able to predict rainfall deficits in this region. While the models said East Africa would become wetter, observations showed substantial declines in the spring wet season. And to be fair, he added, the group’s long-range weather prediction capabilities were still in their infancy. “We made an accurate forecast, but we didn’t understand very well what was going on scientifically,” Funk said. “Now, following our success in 2016/17, and extensive outreach efforts, the humanitarian relief community appreciates the value of our early warning systems.”
In the intervening 10 years, the researchers have worked to discern and understand the broad, often distant mechanisms that drive drought in the Eastern Horn of Africa and create accurate, tailored forecasts for the region. They built on research showing that increased rainfall around Indonesia, caused by anthropogenic increases in sea surface temperatures, resulted in less moisture flowing on to the East African coast during the rainy months. These changes in moisture flows drive back-to-back droughts. But as climate change increases western Pacific sea surface temperatures, it becomes more and more possible to predict devastating water shortages.

Researchers at the University of Illinois Chicago have identified a process by which enzymes can help prevent heart damage in chemotherapy patients.
The enzymes are normally found in a cell’s mitochondria, the powerhouse that produces energy. But when heart cells are put under stress from certain types of chemotherapy drugs, the enzymes move into the cell’s nucleus, where they are able to keep the cells alive. The paper is published in Nature Communications.
“As chemotherapy has become more and more effective, we have more and more cancer survivors. But the tragic part is that a lot of these survivors now have problems with heart failure,” explained co-senior author Sang Ging Ong, assistant professor of pharmacology and medicine.
This has led to the rise of a field called cardio-oncology. Most previous research in the field focused on the mechanisms by which chemotherapy drugs damaged the mitochondria of heart cells. This research team was interested in investigating a different angle: Why do some patients’ hearts escape damage? Is there something particular about their cells that is protecting them?
First the team discovered that when the heart cells were stressed by chemotherapy, the mitochondrial enzymes moved into the cell’s nucleus — an unusual phenomenon. But they didn’t know if that movement was the cause of the cell’s damage or the means of its protection, explained Dr. Jalees Rehman, co-senior author, Benjamin Goldberg Professor and head of the UIC Department of Biochemistry and Molecular Genetics.
“We really didn’t know which way it would go,” he said.
To find out, the researchers generated versions of the enzymes that would specifically move into the nucleus and bypass the mitochondria. They discovered that this relocation fortified the cells, keeping them alive. They demonstrated that this process worked in both heart cells generated from human stem cells and in mice exposed to chemotherapy.

Hardship experienced by mothers during their own childhood or during pregnancy is reflected in the composition of their 2-year-old children’s gut microbiomes, reports an international team of scientists led by UCLA psychologists.
The researchers found small to medium changes in the children’s microbiomes. The research is the first to document the transgenerational effects of adversity on the human gut microbiome.
A growing body of evidence links the gut microbiome to brain and immune functioning, and according to the researchers, changes to that community of microorganisms is likely among the ways that hardship affects children’s socioemotional development.
The study, which is published in Proceedings of the National Academy of Sciences, builds on previous research in rodents, which has shown that that prenatal stress disrupts maternal vaginal and gut microbiomes. Because babies acquire their first gut microbes passing through their mother’s birth canal, mothers’ microbiomes form the basis of their offspring’s.
Previous research in humans has shown that shortly after birth, stress experienced by the infant while in the womb and the mother’s own psychological distress influence the infant microbiome. And while it was known that the effects of prenatal stress on rodent microbiomes persist into adulthood, scientists did not yet know how long after birth the disturbances remain in humans, or whether they affected the next generation.
The study investigated the consequences of maltreatment to mothers during their childhoods, anxiety while pregnant and their children’s exposure to stressful life events in 450 mother-child pairs in Singapore when the children were 2 years old. The researchers asked mothers to recall abuse, neglect or other maltreatment they experienced during childhood, and mothers were screened for anxiety during the second trimester of pregnancy.
Researchers also interviewed the children’s primary caregivers to learn about stressful events that the children had experienced, and their general behavior and health, during their first two years of life, and researchers collected stool samples from the children. The researchers controlled for family income, which often serves as a proxy for childhood adversity.

New work by scientists in the U.S. and China shows how a fertilized egg cell, or zygote, hits ‘reset’ so that the newly formed embryo can develop according to its own genetic program. The study was published July 17 in Nature.
It has been known for some time that the genome of a newly fertilized egg cell is inactive and has to be woken up, said Richard Schultz, research professor at the University of California, Davis, School of Veterinary Medicine and a corresponding author on the paper. This step is called zygote genome activation.
“For the embryo to develop, the oocyte/egg has to lose its identity and does so by making new stuff,” Schultz said. “We now know the first steps in how this transition occurs.”
For the resetting or awakening process to occur, the embryo needs to start transcribing genes from its DNA into messenger RNA that are in turn translated into proteins. The first genes transcribed will activate other genes, implementing the program that will allow the embryo to develop into a complete mouse (or human). The identity of those first master-regulator genes has been unknown until now.
“This is something that has puzzled me for a long time,” Schultz said.
RNA polymerase II (Pol II) is the enzyme that transcribes DNA to RNA. But Pol II by itself is a dumb enzyme, Schultz said. Other genes, called transcription factors, are needed to instruct Pol II so that it transcribes the “correct” genes at the right time.
In the early 2000s, Schultz had the insight that those first transcription factors would be found among dormant maternal messenger RNAs in the egg cell. Dormant maternal messenger RNAs are unique to oocytes because the newly synthesized messenger RNA is not translated as it is in somatic cells. As the oocyte matures to become an egg, these dormant maternal messenger RNAs are translated into proteins that then execute their function. Schultz realized that the information to start zygote genome activation would be in a dormant messenger RNA from the mother that would encode a master transcription factor.

Around one third of people with heart disease suffer from sleep problems. In a paper published in the journal Science, a team at the Technical University of Munich (TUM) shows that heart diseases affect the production of the sleep hormone melatonin in the pineal gland. The link between the two organs is a ganglion in the neck region. The study demonstrates a previously unknown role of ganglia and points to possible treatments.
The fact that melatonin levels can decrease in patients with diseases of the heart muscle, for example after a heart attack, has been known for some time. This has generally been seen as a further example of how a heart condition acts systemically on the entire body. A team working with Stefan Engelhardt, Professor of Pharmacology and Toxicology at TUM, and first author Dr. Karin Ziegler, has now shown that there is a direct cause behind sleep disturbances in people suffering from heart conditions.
Ganglia as “electrical switchboxes”
“In our work, we show that the problems with the heart muscle affect an organ that would seem at first glance to have no direct link to it,” says Stefan Engelhardt. Melatonin is produced in the pineal gland, located inside the brain. Like the heart, it is controlled through the autonomic nervous system, which regulates involuntary processes in the body. The related nerves originate in the ganglia, among other places. Particularly important for the heart and pineal gland is the superior cervical ganglion.
“To get a clear sense of our results, imagine the ganglion as an electrical switchbox. In a patient suffering from sleep disturbances following a heart disease, you can think of a problem with one wire causing a fire to break out in the switchbox and then spreading to another wire,” says Stefan Engelhart.
Nerve connection to pineal gland destroyed in mice and humans
The team discovered that macrophages — cells that eat dead cells — accumulate in the cervical ganglion of mice with heart disease. The exact mechanisms behind this are still unknown. The macrophages cause inflammation and scarring in the ganglion and the destruction of nerve cells. In mice, as in humans, long fibers extending from these nerve cells, called axons, lead to the pineal gland. At advanced stages of disease, there was a substantial decrease in the number of axons connecting the gland to the nervous system. There was less melatonin in the bodies of the animals and their day/night rhythm was disrupted.

The NewsPresident Biden has picked Dr. Paul Friedrichs, a military combat surgeon and retired Air Force major general who helped lead the Covid-19 response at the Pentagon, to head a new White House office created by Congress to prepare for and manage future biological threats.The White House said that it would announce the appointment on Friday and that it would take effect on Aug. 7. It will then be up to Dr. Friedrichs to set up the new office, the Office of Pandemic Preparedness and Response Policy, although the administration has christened it with a shorter Washington acronym: O.P.P.R.The appointment comes after a lengthy search for a director that ended where it began — at the White House, where Dr. Friedrichs recently joined the staff of the National Security Council as the senior director for global health security and biodefense. Before that, he served as the Joint Staff surgeon at the Pentagon, providing medical advice to the chairman of the Joint Chiefs of Staff. His planned selection was reported last week by The Washington Post.Dr. Paul Friedrichs at the Pentagon in 2021. He retired from the Air Force as a major general and recently joined the staff of the National Security Council.Alex Brandon/Associated PressWhy It Matters: Future health threats loom.The coronavirus pandemic has often been described as the worst public health crisis in a century. But experts agree that given current migration patterns and the way humans intersect with animal life, it will not be a century — and it might not even be a decade — before the next pandemic arrives.The era of Covid “czars” is over. Mr. Biden’s first White House coronavirus response coordinator, Jeffrey D. Zients, is now the White House chief of staff. The second coordinator, Dr. Ashish K. Jha, has gone back to his position as dean of the Brown University School of Public Health. Mr. Zients praised Dr. Friedrichs for his work on the pandemic, saying he would “lead the charge to ensure that never happens again.”Covid-19 made clear that a biological health threat does not respect boundaries — including the boundaries that divide federal agencies. The appointment of Dr. Friedrichs signals a more permanent and coordinated effort to prepare for and respond to pandemics — one that will last beyond the Biden administration and will be centralized within the White House.Background: Dr. Friedrichs served decades in the Air Force.In a February speech, Dr. Friedrichs reflected on his 37-year career in the Air Force and shared a bit about himself. His father served in the Navy at the end of World War II, and his mother was a Hungarian freedom fighter whose parents were killed by the Russians. His wife was an Army doctor when they met.He also reflected on the role of the military in fighting Covid-19, an effort that included helping to develop and distribute vaccines and providing medical support to struggling hospitals. “The military health system became the pinch-hitter that stepped in to help our civilian partners as we collectively struggled to work through that pandemic,” he said.What’s Next: The job will focus on preparedness.Dr. Friedrich’s new position gives him authority to oversee domestic biosecurity preparedness. He will need to work on the development of next-generation vaccines, ensure adequate supplies in the Strategic National Stockpile and ramp up surveillance to monitor for new biological threats. He will also have to work with Congress to secure funding for preparedness efforts.

Like us, cells communicate. Well, in their own special way. Using waves as their common language, cells tell one another where and when to move. They talk, they share information, and they work together — much like the interdisciplinary team of researchers from the Institute of Science and Technology Austria (ISTA) and the National University of Singapore (NUS). They conducted research on how cells communicate — and how that matters to future projects, e.g. application to wound healing.
What comes to your mind when you think of biology? Animals, plants, theoretical computer models? The last one, you might not associate with it right away, although it is a major part of biological research. It is precisely these calculations that help to understand complex biological phenomena, down to the most concealed details. ISTA Professor Edouard Hannezo applies them to understand physical principles in biological systems. His group’s latest work gives novel insights into how cells are moving and communicating inside living tissue.
During his PhD, Daniel Boocock, along with Hannezo and long-term collaborator Tsuyoshi Hirashima from the National University of Singapore, developed a detailed new theoretical model, which is published today in the journal PRX Life. It allows a better understanding of long-range cell-cell communication and describes both the complex mechanical forces the cells apply to each other and their biochemical activity.
Cells communicate in waves
“Let’s say you have a Petri dish that is covered with cells — a monolayer. They appear to just sit there. But the truth is they move, they swirl, and they spontaneously make chaotic behaviors,” Hannezo explains.
Similar to a dense crowd at a concert, if one cell pulls on one side, another cell senses the action and can react by either going in the same direction or pulling the opposite way. Information can then propagate and travel in waves — waves that are visible under a microscope. “Cells not only sense mechanical forces but also their chemical environment — forces and biochemical signals cells are exerting on each other,” Hannezo continues. “Their communication is an interplay of biochemical activity, physical behavior, and motion; however, the extent of each mode of communication and how such mechanochemical interplays function in living tissues has been elusive until now.”
Predicting movement patterns
Driven by the wave visuals, the scientists’ goal was to establish a theoretical follow-up model that would validate their previous theory on how cells move from one region to the next. Daniel Boocock explains, “In our earlier work, we wanted to uncover the biophysical origin of the waves and whether they play a role in organizing collective cell migration. However, we hadn’t considered the liquid-solid transition of the tissue, the noise inherent in the system, or the detailed structure of the waves in 2D.”