This finding is unexpected because the plate tectonic regime of our planet progressively recycles crustal material via large-scale mantle convection at much smaller time scales. Therefore, it has been assumed that vestiges of early geological processes on Earth can only be found as analogues, on other terrestrial planets (Mercury, Venus, and Mars), asteroids, or the Moon. However, according to their study ‘Long-term preservation of Hadean protocrust in Earth’s mantle’, which has recently appeared in the Proceedings of the National Academy of Sciences (PNAS), magmatic rocks that erupted throughout Earth’s history can still carry signatures that provide detailed information about the nature of the first crust, its long-term preservation in a graveyard in the lower-most mantle, and its resurrection via younger volcanism.

For their study, the geologists investigated up to 3.55 billion years old rocks from southern Africa. The analysis of these rocks revealed small anomalies in the isotope composition of the element tungsten (W). The origin of these isotope anomalies, namely the relative abundance of ¹⁸²W, relates to geological processes that must have occurred immediately after the formation of the Earth more than 4.5 billion years ago.

Model calculations by the authors show that the observed ¹⁸²W isotope patterns are best explained by the recycling of Earth’s earliest crust into mantle material that ascends via plumes from the lower mantle to generate lavas erupting at Earth’s surface. Intriguingly, the study shows that similar isotope patterns can be observed in distinct types of modern volcanic rocks (ocean island basalts), which demonstrates that Earth’s earliest crust is still buried in the lowermost mantle.

‘We assume that the lower layers of the crust — or the roots of the primordial continents — became heavier than their surroundings due to a geological maturation process and therefore sank into the Earth’s underlying mantle. Similar to a lava lamp,’ geochemist Dr Jonas Tusch from the University of Cologne’s Institute of Geology and Mineralogy remarked. ‘This fascinating insight provides a geochemical fingerprint of the young Earth, allowing us to better understand how large continents formed over the history of our planet. It also explains how our current, oxygen-rich atmosphere evolved — setting the stage for the origin of complex life,’ Dr Elis Hoffmann of Freie Universität Berlin added.

The geochemical fingerprint of the early Earth can also be compared with findings about other planets obtained during space missions. For example, data from Mars missions and studies of Martian meteorites show that Mars still has a very old surface due to the lack of plate tectonics, and that its composition may correspond to that of the young Earth.

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Some people with COVID-19 experience the disease more severely than others. Previous research has identified certain variants in specific human genes that are associated with a person experiencing more severe COVID-19. Some of these variants may also be associated with other medical conditions that may already be well understood; identifying these shared variants could improve understanding of COVID-19 and illuminate potential new paths for treatment.

To identify shared variants, Verma and colleagues used an unprecedented dataset of genotypic information linked to electronic health record data (EHR) for more than 650,000 U.S. veterans. They conducted a type of analysis known as a phenome-wide association study (PheWAS) to examine links between variants often found in Veterans who experienced severe COVID-19 and variants associated with a broad selection of medical conditions.

The analysis revealed that certain variants associated with COVID-19 are also associated with known risk factors for COVID-19. Particularly strong links were found for variants associated with venous embolism and thrombosis, as well as type 2 diabetes and ischemic heart disease — two known COVID-19 risk factors.

The analysis also found genetic links between severe COVID-19 and neutropenia for Veterans of African and Hispanic ancestry; these links did not appear for those of European ancestry.

Among respiratory conditions, idiopathic pulmonary fibrosis and chronic alveolar lung disease shared genetic links with severe COVID-19, but other respiratory infections and chronic obstructive pulmonary disease (COPD) did not. Some variants associated with severe COVID-19 were also associated with reduced risk of autoimmune conditions, such as psoriasis and lupus. These findings highlight the need to carefully weigh various aspects of the immune system when developing new treatments.

Despite some limitations of the PheWAS method, these findings could help deepen understanding of COVID-19 and guide development of new treatments.

Verma concludes, “The study demonstrates the value and impact of large biobanks linking genetic variations with EHR data in public health response to the current and future pandemics. MVP is one of the most diverse cohorts in the US. We had a unique opportunity to scan thousands of conditions documented before the COVID-19 pandemic. We gained insights into the genetic architecture of COVID-19 risk factors and disease complication.”

“One thing that stood out to us was the high number of immune-mediated conditions that shared genetic architecture with severe manifestations of COVID-19,” coauthor Katherine Liao adds. “The nature of the associations brought to light how the SARS-CoV2 virus pushes on a pressure point in the human immune system and its constant balancing act of fighting infection while maintaining enough control so that it does not also become an autoimmune process, attacking self.”

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The Centers for Disease Control estimates that the bacterium causes approximately 500,000 infections in the United States annually, with severe diarrhea and colitis (inflammation of the colon) as characteristic symptoms.

The researchers’ findings are published in the April 27, 2022 online issue of PNAS.

C. difficile is the most dominant cause of hospital-associated infections, in part from the use of antibiotics, which can kill enough healthy bacteria to allow C. difficile to grow unchecked. Infections are particularly dangerous in older persons. One in 11 people over the age of 65 who are diagnosed with a hospital-associated case of C. difficile die within one month, reports the CDC.

“C. diff is persistent and pervasive,” said senior author Jonathan M. Monk, PhD, a research scientist in the Systems Biology Research Group at UC San Diego, directed by Bernhard O. Palsson, PhD, professor of bioengineering and an adjunct professor in the UC San Diego School of Medicine. “It doesn’t cause typical diarrhea. Most people do recover, but some become seriously ill, require hospitalization and some die from complications like kidney failure or sepsis.”

To better understand the genetic features of C. difficile — and thus develop models that can identify and predict its complex and constant evolution — researchers used whole-genome sequencing, high-throughput phenotypic screening and metabolic modeling of 451 bacterial strains.

This data was used to construct a “pangenome” or entire set of genes representative of all known C. difficile strains, from which they identified 9,924 distinct gene clusters, of which 2,899 were considered to be core (found in all strains) while 7,025 were “accessory” (present in some strains but missing in others).

Using a new typing method, they categorized 176 genetically distinct groups of strains.

“Typing by accessory genome allows for the discovery of newly acquired genes in genomes of pathogens that may otherwise go unnoticed with standard typing methods,” said co-author Jennifer K. Spinler, PhD, an instructor in pathology and immunology at the Baylor College of Medicine. “This could be critical in understanding what drives an outbreak and how to fight its spread.”

Thirty-five strains representing the overall set were experimentally profiled with 95 different nutrient sources, revealing 26 distinct growth profiles. The team then built 451 strain-specific genome scale models of metabolism to computationally produce phenotype diversity in 28,864 unique conditions. The models were able to correctly predict growth in 76 percent of measured cases.

“One of the strengths of the presented work is the cohesion of distinct biological data types into comprehensive systems biology frameworks that enable analysis at scale,” said first author Charles J. Norsigian, PhD, a data scientist in the Systems Biology Research Group. “By interpreting strains of C. difficile in a population context, we were able to bring to light pertinent strain features regarding nutrient niche, virulence factors, and antimicrobial resistance determinants that might have otherwise gone undetected.”

Co-authors include: Bernhard O. Palsson, UC San Diego; Heather A. Danhof, Colleen K. Brand, Firas S. Midani, Robert A. Britton and Tor C. Savidge, Baylor College of Medicine; and Jared T. Broddrick and Jennifer K. Spinier, NASA Ames Research Center.

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“Despite the common experience of swallowing medications orally, there is a huge number of therapies that are not available orally,” says Khatcher Margossian, the lead author of the study and a candidate for a dual M.D./Ph.D. from Rush Medical College and the UMass Amherst Department of Polymer Science and Engineering, respectively. This is because there are many drugs that can’t withstand the stomach’s harshly acidic environment. Two ways around this problem are to either inject or implant medications; but in both cases, the pain, fear and potential side effects can limit a patient’s willingness to undergo treatment or to stick with the treatment plan through its full course. And even those drugs that are strong enough to withstand the stomach’s acid and make it through to the small intestine, where they can be absorbed into the bloodstream, often do not make it through entirely intact. “The doses of oral medications are usually larger than what our body really needs,” explains Murugappan Muthukumar, the Wilmer D. Barrett Professor in Polymer Science and Engineering at UMass Amherst and the study’s senior author. “This is because some of the medication decomposes in the stomach.”

“If there were some way to protect this precious therapeutic cargo,” says Margossian, “we could expand the library of medications that we can deliver orally.” Figuring out how to protect the precious cargo is exactly what Margossian, Muthukumar, and their colleagues have done.

The study, recently published in Nature Communications, details a new class of material, called a pZC, which forms through a process known as “complex coacervation.” In their system, two types of charged polymers, a polyzwitterion and a polyelectrolyte, associate to form a protective droplet inside of which medications can travel. The trick that the pZC has to perform is that it not only needs to be tough enough to withstand the highly acidic stomach environment, it also has to disassemble in the much gentler, neutral conditions of the small intestine.

Paradoxically, the key to the group’s success was not to strengthen the bonds between the polyzwitterion and polyelectrolyte but to weaken them. “Weakening the association between the two materials,” says Muthukumar, “allows us to control precisely when they come apart. If the bonds are too strong, then there’s no room to play.”

The group’s research is driven by the real-life needs of medical practitioners. Not only will these materials allow clinicians to more efficiently deliver the right dosages of drugs, but they will vastly increase the number of medications that can be taken orally. “This is a foundational technology that can alter how we treat disease,” says Margossian. “We hope that our work will make its way into clinicians’ hands and help them save lives.”

This research was supported by the National Science Foundation and the Air Force Office of Scientific Research.

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