In August 2021, a magnitude 7.5 earthquake hit near the South Sandwich Islands, creating a tsunami that rippled around the globe. The epicenter was 47 kilometers below the Earth’s surface — too deep to initiate a tsunami — and the rupture was nearly 400 kilometers long, which should have generated a much larger earthquake.

Seismologists were puzzled and sought to understand what really happened that day in the remote South Atlantic.

A new study revealed the quake wasn’t a single event, but five, a series of sub-quakes spread out over several minutes. The third sub-quake was a shallower, slower magnitude 8.2 quake that hit just 15 kilometers below the surface. That unusual, “hidden” earthquake was likely the trigger of the worldwide tsunami.

The study was published in the AGU journal Geophysical Research Letters, which publishes short-format, high-impact papers with implications that span the Earth and space sciences.

Because the South Sandwich Islands earthquake was complex, with multiple sub-quakes, its seismic signal was difficult to interpret, according to lead study author Zhe Jia, a seismologist at the California Institute of Technology. The magnitude 8.2 quake was hidden within the tangle of seismic waves, which interfered with each other over the course of the event. The hidden quake’s signal wasn’t clear until Jia filtered the waves using a much longer period, up to 500 seconds. Only then did the 200-second-long quake, which Jia said accounted for over 70% of the energy released during the earthquake, become clear.

“The third event is special because it was huge, and it was silent,” Jia said. “In the data we normally look at [for earthquake monitoring], it was almost invisible.”

Predicting hazards for complex earthquakes can be difficult, as the South Sandwich Islands quake demonstrates. The USGS initially reported the magnitude 7.5 quake and only added the 8.2 event the following day, as the surprise tsunami lapped on shores up to 10,000 kilometers away from its point of origin.

“We need to rethink our way to mitigate earthquake-tsunami hazards. To do that, we need to rapidly and accurately characterize the true size of big earthquakes, as well as their physical processes,” Jia said.

Because this type of earthquake can result in unexpected tsunami, it’s critical to improve our predictions. “With these complex earthquakes, the earthquake happens and we think, ‘Oh, that wasn’t so big, we don’t have to worry.’ And then the tsunami hits and causes a lot of damage,” said Judith Hubbard, a geologist at the Earth Observatory of Singapore who was not involved in the study. “This study is a great example of how we can understand how these events work, and how we can detect them faster so we can have more warning in the future.”

Sneaky seismic signals

When an earthquake hits, it sends waves of vibration through the Earth. The global network of earthquake monitors uses those seismic waves to pinpoint the time, location, depth and magnitude of an earthquake. Common monitoring often focuses on short- and medium-periods of waves, Jia said, and longer periods can be left out. But even incorporating long periods into monitoring, on its own, isn’t enough to catch complex earthquakes with messy seismic signals.

“It’s hard to find the second earthquake because it’s buried in the first one,” Jia said. “It’s very seldom complex earthquakes like this are observed. … And if we don’t use the right dataset, we cannot really see what was hidden inside.”

A simple earthquake can easily be pinpointed and described, Jia said. But a messy one needs to be carefully broken down into its constituent parts, to find out what unique combination of simpler earthquakes built up the complex one.

Jia and his colleagues developed an algorithm to tease apart the seismic signals during those messy earthquakes. By “decomposing” complex earthquake signals into simpler forms, using waves over different periods (varying from 20 to 500 seconds long), the algorithm can identify the location and properties of different sub-earthquakes. It’s akin to someone with perfect pitch hearing five dissonant notes struck at once, yet being able to identify each individual note.

“I think a lot of people are daunted by trying to work on events like this,” said Hubbard. “That somebody was willing to really dig into the data to figure it out is really useful.”

Both Jia and Hubbard noted a long-term goal is to automate the detection of such complex earthquakes, as we can for simple earthquakes. For the 2021 quake, the tsunami was small by the time it reached shores, and most of the permanent residents of the remote, volcanic islands are penguins. But complex earthquakes can pose significant hazards if they generate larger tsunami or strike in a densely populated region.

“Thriving on top of extinct volcanic seamounts of the Langseth Ridge we found massive sponge gardens, but did not know what they were feeding on,” reports Antje Boetius, chief scientist of the expedition, head of the Research Group for Deep Sea Ecology and Technology at the Max Planck Institute for Marine Microbiology and director of the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research. Using samples from the mission, first-author Teresa Morganti, sponge expert from the Max Planck Institute for Marine Microbiology in Bremen was able to identify how sponges adapt to the most nutrient-poor environment. Morganti explains: “Our analysis revealed that the sponges have microbial symbionts that are able to use old organic matter. This allows them to feed on the remnants of former, now extinct inhabitants of the seamounts, such as the tubes of worms composed of protein and chitin and other trapped detritus.”

Living on the leftovers

Sponges are considered to be one of the most basal forms of animal life. They are nevertheless successful and abundant in all oceans, from shallow tropical reefs to the arctic deep-sea. Many sponges accommodate a complex community of microorganisms in a symbiotic relationship, which contributes to the health and nutrition of the sponges by producing antibiotics, transferring nutrients and disposing of excretions. This also goes for Geodia-sponges, which dominated the community on the Arctic seamounts. The unity of sponge and associated microbes is called a sponge holobiont. Teresa Morganti cooperated with Anna de Kluijver, an expert from Utrecht University, and with the lab of Gesine Mollenhauer at the Alfred Wegener Institute to identify the food source, the growth and the age of the sponges. They learned that thousands of years ago, substances seeping from the seabed’s interior were supporting a rich ecosystem, home to a variety of animals. When they died out, their remnants remained. Now these form the base of this unexpected sponge garden.

Microbial analysis of the microorganisms supported the researchers’ hypothesis. “The microbes have just the right toolbox for this habitat,” explains Ute Hentschel from the GEOMAR Helmholtz Centre for Ocean Research in Kiel, who carried out the microbiological analyses with her team. “The microbes have the genes to digest refractory particulate and dissolved organic matter and use it as a carbon and nitrogen source, as well as a number of chemical energy sources available there.”

The scientists also showed that the sponges act as ecosystem engineers: They produce spicules that form a mat on which they crawl. This may further facilitate the local settling of particles and biogenic materials. The sponge holobionts can tap into this detrital matter, thus creating their own food trap.

Protecting requires understanding

Langseth Ridge is an underwater mountain range not far from the North Pole that sits beneath the permanently ice-covered water’s surface. There, sponge biomass was comparable to that of shallower sponge grounds with much higher nutrient input. “This is a unique ecosystem. We have never seen anything like it before in the high Central Arctic. In the study area, primary productivity in the overlying water provides less than one percent of the sponges’ carbon demand. Thus, this sponge garden may be a transient ecosystem, but it is rich in species, including soft corals,” says Antje Boetius.

The Arctic is one of the most affected regions by climate change. “Prior to our study, no similar sponge ground has been identified in the high Central Arctic, an area of the ice-covered ocean which remains understudied given the difficulties associated with observing and sampling such ice- covered deep-sea ecosystems,” Morganti stresses. The close cooperation of scientists from different institutions, including the Max Planck Institute for Marine Microbiology, the Alfred Wegener Institute and GEOMAR, enabled a comprehensive understanding of this surprising hotspot of life in the cold deep. “With sea-ice cover rapidly declining and the ocean environment changing, a better knowledge of hotspot ecosystems is essential for protecting and managing the unique diversity of these Arctic seas under pressure,” concludes Boetius.

Publishing in the Proceedings of the National Academy of Sciences, Yasir Suhail, a postdoctoral researcher working alongside Kshitiz, assistant professor in the Department of Biomedical Engineering, uncovered regulatory sequences in the genomes of mammals including cows, pigs, horses, and humans that explain how endometrium is invaded by the placenta, and how normal tissue is invaded by cancer.

Suhail and Kshitiz were joined in their efforts by Gunter Wagner, professor in evolutionary biology and ecology at Yale University.

In many mammals including humans, the placenta invades the wall of the uterus during pregnancy in the same way that cancer cells invade surrounding tissues.

“When you look at a picture of placentation, it looks eerily similar to cancer in any other part of the body,” says Kshitiz, “Even the molecular mechanisms are quite similar. This is quite a contrast from cows and horses, where the placenta does not invade into the mother. In these mammals, cancer cells also do not invade into their surroundings as they do in humans.”

Kshitiz, along with Gunter Wagner and Andre Levchenko at Yale first drew the comparison between cancer metastasizing in cows and humans in a seminal finding in Nature Ecology & Evolution. Looking at cells from the endometrium of various species, Kshitiz found that in order to resist invasion of the placenta, certain species have evolved over time to make their stromal cells — the connective tissue cells in an organ — highly resistant to any invasion.

The latest research is a deeper dive into the comparative genetics between mammals, which shows how changes in genetic regulation informs this resistance in cows and horses and makes humans vulnerable to cancer malignancy. With comparative data generated by Wagner and Jamie Maziarz at Yale, Suhail developed a model to identify how the binding of transcription factors — the proteins that regulate the expression of genes — explain changes in resistance to invasion across different species of mammals.

“Our new framework identifies key transcription factors and examines how their targets differ from cows, pigs, and horses to humans,” says Suhail. “What we learned from other species has direct applications in advancing our understanding of human cancer.”

Suhail used the genomic sequences and gene expression information to predict specific signaling proteins that drive the expression of genes that decrease the susceptibility of invasion in human cells. Using a custom fabricated bio chip, the researchers were able to confirm that these predicted proteins did in fact decrease the invasion of both cancer and placental cells. Evolutionary predictions across species are difficult to test experimentally, so confirmation of the theory experimentally is very satisfying to the researchers.

“We all think about human cancers are an outcome of cancer cells themselves. But what we’ve proposed is that mammals have very different mechanisms to resist cancer spread, and that these mechanisms have actually been derived to resist fetal invasion into the mother,” Kshitiz says. “To be vulnerable to malignancy may partly be an evolutionary compromise to allow an invasive pregnancy.”

While other researchers are targeting cancer and immune cells, Kshitiz’s lab focuses on how healthy cells limit cancer growth around them. This approach can help us rethink the way we approach cancer therapies.

“This study identifies specific genetic regulatory mechanisms which explain these differences, and point us towards many directions to rethink about anti-cancer therapy, from those that kill cancer to creating new therapies which “contain” cancer within its boundaries.”

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Materials provided by University of Connecticut. Original written by Courtney Chandler. Note: Content may be edited for style and length.

NAFLD is a condition where excess fat builds up in liver tissue for reasons unrelated to alcohol consumption. If untreated, the excess fat can lead to inflammation, scarring and increased risk of liver cancer. The incidence of NAFLD is increasing among children and adolescents, with 10% of children in the U.S. currently affected. This number is expected to increase within the next decade.

“We know that development of NAFLD is partly to do with diet and lack of exercise, but there is an environmental component that primes an infant’s liver to develop it as well; specifically, the metabolic state of the mother,” says Michael Cowley, associate professor of biology at NC State and corresponding author of the work.

Metabolic syndrome, or MetS, is a catchall term for a number of health issues including high blood sugar, obesity and elevated blood pressure. Previous studies had shown a link between MetS in mothers and increased NAFLD susceptibility in infants.

“We wanted to look specifically at mothers with MetS to see whether infants are affected pre- or post-natally, and tease out what is happening on the molecular level to trigger the disease,” Cowley says.

In a mouse model of MetS, Cowley and his colleagues compared offspring of mice with MetS to those from control mice, or mice without MetS. They studied four groups: offspring of control mice nursed by control mice, offspring of MetS mice nursed by MetS mice, and cross-fostered offspring from both groups. Cross-fostered means that the offspring of one group were nursed by mothers from the other group. They compared offspring at birth and at three weeks after birth, just before weaning.

They found that mice born to MetS mothers and nursed by control mice did not develop NAFLD, whereas most mice from both control and MetS groups nursed by MetS mothers did.

Using RNA sequencing, the researchers found that the imprinted gene network (IGN), including its regulator, an imprinted gene called Zac1, was upregulated, or more active, in mice nursed by the MetS mothers.

Imprinted genes are a small set of genes which are expressed from a single parental allele. Most genes consist of two copies (one inherited from each parent) which activate and influence inherited traits. Imprinted genes are expressed by a single active copy, and have been shown to be susceptible to changes in environmental factors.

“Zac1 is acting as the master switch here,” Cowley says. “It was activated in pups that nursed from MetS mothers, and this has downstream effects in the IGN that lead to an increased susceptibility to NAFLD.

“Researchers have proposed that imprinted genes play a role in this process — we’re showing here that they do,” Cowley continues. “The work also confirms the post-natal environment is more important to the development of the disease than pre-natal exposure. Our next steps will involve looking at what happens once potential environmental stressors such as the mother’s milk are removed. Can Zac1 be switched off again?”

The research appears in Hepatology and was supported by the National Institutes of Health (grant numbers K22ES027510, R01ES031596, P30ES025128 and P30DK034987) and by Oak Ridge Associated Universities through a Ralph E. Powe Junior Faculty Enhancement Award. Marine Baptissart, former postdoctoral researcher at NC State, is first author.

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Materials provided by North Carolina State University. Original written by Tracey Peake. Note: Content may be edited for style and length.

The survival rate for children with ALL has increased impressively to over 80% over the last several decades. However, the prognosis for children whose cancer recurs remains unfavorable. Therefore, minimal residual disease (MRD) monitoring is an important prognostic factor for treatment response and patient stratification. MRD monitoring uses highly sensitive real-time PCR to measure the amount of cancer cells among normal cells.

“MRD markers can disappear during treatment, which can lead to false-negative results and poor decision-making in personalized treatments,” explains Principal investigator Cornelia Eckert, PhD, Department of Pediatric Oncology/Hematology, Charité — Universitätsmedizin Berlin, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ). Consequently, monitoring at least two independent markers per patient is recommended. Dr. Eckert continues, “The current gold standard EuroMRD consortium guidelines call for amplification using singleplex real-time PCR quantification, making testing additional markers more laborious and expensive. They also lead to a higher consumption of patient material.”

To overcome these limitations, Dr. Eckert and co-investigators established the personalized MP PCR, an iterative workflow and guidelines for designing multiplex real-time PCRs to monitor up to four MRD markers for ALL simultaneously in one assay. When tested on DNA in bone marrow samples from patients with ALL, the MP PCRs met the EuroMRD gold standard guidelines and level of sensitivity for clinical decision-making.

Co-investigator Michael Lehnert, PhD, Hahn-Schickard Freiburg, states, “Multiplexing can significantly improve personalized MRD monitoring of patients, because a higher number of MRD markers per patient can be analyzed at the same time. Even though these patient-specific sequences of cancer cells only differ in a few DNA nucleotides from healthy cells, our multiplex assay can still distinguish between these DNA sequences. Therefore, a broader range of patient-specific sequences can be included in the assay.”

The MRD-MP guidelines are simple and may allow assay standardization across different laboratories. To demonstrate the potential transfer of the duplex MP PCR into a routine diagnostic setting, the new assay was applied in a prospectively assessed patient case in comparison with the gold standard singleplex test. Both fulfilled the EuroMRD guidelines and led to a similar quantitative range and sensitivity.

In order to deal with challenges inherent to multiplex PCR, the researchers developed an efficient iterative workflow for PCR design and optimization. DNA primer titration is only involved and extended if the assay performance is not sufficient in the first step, so that the number of iterations is minimized.

“There is a vast variety of DNA marker sequences unique to each leukemia,” adds first author Elena Kipf, PhD, Hahn-Schickard Freiburg. “The MRD-multiplex workflow provides a systematic and reliable way of effective MRD-MP PCR design and optimization and helps the standardization of personal diagnostics.”

While their work demonstrates that multiplex MP PCR has the potential to set a new standard in personalized MRD monitoring, the researchers note it must be clinically validated in a representative cohort of ALL patients. “Cancer is a fatal disease from which not every patient can be cured,” Dr. Eckert stresses. “After successful clinical validation, patients could benefit from extended MRD monitoring, leading to more precise predictions of therapy response and better patient stratification and outcomes.”

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Materials provided by Elsevier. Note: Content may be edited for style and length.