“Ribonucleic acid or RNA is one type of genetic material that is present inside all living cells. It is mostly known to act as a messenger carrying instructions encoded in the DNA for the synthesis of proteins,” said co-corresponding author, Dr. Aleksandar Milosavljevic, professor and Henry and Emma Meyer Chair in Molecular Genetics at Baylor. He also is the director of the Graduate Program in Quantitative & Computational Biosciences and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. The Milosavljevic Lab is the host of the exRNA Atlas, the data management and resource repository of the Extracellular RNA Communication Consortium, an NIH Common Fund project exploring the biology of exRNA.

In recent years research has shown that RNA not only exists inside cells, but also is exported from cells as extracellular RNA and plays a role in cell-to-cell communication.

“ExRNAs exist in bodily fluids outside of cells where they can associate with a variety of carriers including RNA binding proteins (RBPs), but the cargo and distribution of RBPs across biofluids is largely unknown,” said coauthor Robert Fullem, a graduate student in the Milosavljevic lab. “Our goal in this study was to fill that gap. This major gap in knowledge limited our understanding of the role of RBPs as carriers of exRNA in human bodily fluids. Our findings open a new road toward understanding exRNA biology and provide new opportunities for the development of exRBP/exRNA liquid biopsy biomarkers.”

The researchers applied computational analyses to identify exRBPs in plasma, serum, saliva, urine and cerebrospinal fluid. The computational predictions were validated experimentally at about 80% in both plasma and cell cultures in the lab, suggesting high specificity for the computational method.

“With this information, we developed a map of candidate exRBPs and their exRNA cargo in bodily fluids expanding the landscape of potential biomarkers that can now be studied in liquid biopsies and used to track normal and disease processes,” Milosavljevic said. “We present this map as a resource available at no cost to the scientific community.”

Other contributors to this work include co-first authors Emily L. LaPlante and Alessandra Stürchler, David Chen, Anne C. Starner, Emmanuel Esquivel, Eric Alsop, Andrew R. Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark Gerstein, Roger P. Alexander, Matthew E. Roth, Jeffrey Franklin, Robert Coffey, Robert L. Raffai, Isabelle M. Mansuy, Stavros Stavrakis, Andrew deMello, Louise C. Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu, Jennifer Jones, Kendall Van Keuren-Jensen and Eric Van Nostrand. 

This publication was supported in part by the NIH Common Fund (1UG3TR002881-01, 1U54DA036134-01,1U54DA049098-01, 1U54DA049098-01S1, 1UH3TR002881, OT2OD030547-01S1 and 5UG3TR002881-02). Further support was provided by CPRIT Scholar in Cancer Research grants RR200040, 4UH3CA241703-03, and a Swiss National Center of Competence (NCCR) in Research RNA & Disease grant.

Biocrusts play a crucial role in maintaining soil health and ecosystem sustainability, but they are currently under assault. Human activities including agriculture, urbanization, and off-road vehicle use can lead to the degradation of biocrusts, which have long-term consequences for these fragile environments. Climate change is also placing stress on biocrusts, which struggle to adapt to sunlight and searing heat in arid landscapes like the Sonoran Desert.

Now, Ferran Garcia-Pichel and his student at Arizona State University propose an innovative approach to restoring healthy biocrusts. The idea is to use new and existing solar energy farms as nurseries for generating fresh biocrust.

Safely shielded from the sun beneath arrays of solar panels, like beachgoers under an umbrella, the biocrusts are sheltered from excessive heat and can flourish and develop. Ultimately, the newly generated biocrusts can then be used to replenish arid lands where such soils have been damaged or destroyed.

Help for desert soil

In a proof-of-concept study, ASU researchers adapted a suburban solar farm in the lower Sonoran Desert as an experimental breeding ground for biocrust. During the three-year study, photovoltaic panels promoted biocrust formation, doubling biocrust biomass and tripling biocrust cover compared with open areas with similar soil characteristics.

When biocrusts were harvested, natural recovery was moderate, taking around 6-8 years to fully recuperate without intervention. However, when harvested areas were re-inoculated, the recovery was much faster, with biocrust cover reaching near-original levels within one year.

The researchers emphasize that the use of similar, but larger, solar farms could provide a low-cost, low-impact, and high-capacity method to regenerate biocrusts and expand soil restoration approaches to regional scales. They have dubbed their pioneering approach “crustivoltaics.”

The study estimates that use of the three largest solar farms in Maricopa County, Arizona as biocrust nurseries could empower a small-scale enterprise to rejuvenate all idle agricultural lands within the county, spanning more than 70,000 hectares, in under five years. Among many environmental benefits, this restoration effort has the potential to significantly decrease airborne dust presently impacting the Phoenix Metropolitan region.

“This technology can be a game changer for arid soil restoration,” Garcia-Pichel says. “For the first time reaching regional scales at our fingertips, and we could not be more excited. To boot, crustivoltaics represents a win-win approach for conservation of arid lands and for the energy industry alike.”

Garcia-Pichel is a Regents’ Professor in the School of Life Science and the founding director of the Biodesign Center for Fundamental & Applied Microbiomics. The center amalgamates researchers that study assemblages of microbes (or microbiomes) acting in unison in various settings, from humans to animals and plants, to oceans and deserts. Garcia-Pichel’s lab has specialized in the study and applications of desert soil microbiomes.

The group’s findings appear in the current issue of the journal Nature Sustainability, in a publication co-lead by graduate student Ana “Meches” Heredia-Velásquez, and former graduate student Dr. Ana Giraldo-Silva, now a professor at the Public University of Navarre in Spain. A separate briefing of this contribution appears concurrently in Nature.

Living matrix

Biocrusts are complex ecosystems researchers have only recently begun to explore. Among their many housekeeping functions, they act to stabilize soil by binding soil particles together, minimizing the loss of topsoil caused by wind and water. They contribute to nutrient cycling by fixing atmospheric nitrogen, a process where nitrogen gas is converted into ammonia, making it available to plants. Cyanobacteria, which are present in biocrusts, are the primary organisms responsible for this process.

Photosynthetic activities within biocrusts play a role in carbon storage by fixing atmospheric carbon dioxide. This process can help mitigate some of the effects of climate change by removing carbon dioxide from the atmosphere. Biocrusts also increase the soil’s water-retaining capacity, allowing more water to infiltrate the soil and reducing runoff. This helps to improve water availability for plants and other organisms in arid ecosystems.

Finally, biocrusts support a diverse community of microorganisms that contribute to overall ecosystem biodiversity and resilience.

Drylands, which make up approximately 41% of the Earth’s continental area, are experiencing severe degradation due to human activities and climate change. The communities of microorganisms on soil surfaces are vital to protect and fertilize these soils and are essential for dryland sustainability. However, current biocrust restoration methods involve high effort and low capacity, limiting their application to small areas. Existing methods have struggled to replenish more than a few hundred square meters of land.

Solar solutions

The research suggests that solar farms serve as biocrust hotspots, as the elevated photovoltaic panels create a greenhouse-like microclimate promoting biocrust development. Although crustivoltaics is a slower and weather-dependent method compared to greenhouse-sized biocrust nurseries, it has many advantages. The technique requires fewer resources, minimal management, and no upfront investment. Indeed, the use of crustivoltaics is 10,000 times more cost-effective than current methods, according to the research findings.

The next steps will involve implementing crustivoltaics at regional scales through the cooperation of scientists, collaborative agencies, land users and managers. Use of the technique can provide incentives to solar farm operators, including reduced dust formation on solar panels and increased revenue from carbon credits.

The crustivoltaic approach has the potential to offer a dual-use solution for both solar power generation and biocrust restoration on a large scale, while also providing socioeconomic benefits. This method could play a significant role in the restoration and sustainability of dryland ecosystems.

The results of the joint project, which was funded by the German Federal Ministry of Education and Research (BMBF), are published in the article ‘Stabilization of mineral-associated organic carbon in Pleistocene permafrost’ in the journal Nature Communications.

The Arctic is warming dramatically fast compared to other parts of the world. Much of it is covered by permafrost and contains large amounts of carbon, almost twice as much as the atmosphere. This carbon comes from plants that have grown over thousands of years, decomposed in the soil and then become ‘frozen’. Due to strongly rising temperatures in the Arctic, this gigantic freezer is thawing fast. The old carbon stored in it can now be degraded by microorganisms, releasing carbon dioxide and methane into the atmosphere. These greenhouse gases accelerate global warming. The warmer it gets, the more greenhouse gases are in turn released from the permafrost, causing temperatures to rise further and frozen soils and sediments to thaw even faster. “There is a feedback of carbon in permafrost with climate, the strength of which depends largely on those factors that influence microbial degradation,” said Janet Rethemeyer.

In the joint research project, scientists from the Institute of Zoology at the University of Cologne, the University of Tübingen, the Technical University of Munich and the Alfred-Wegener-Institute in Potsdam studied long permafrost cores from the Siberian Arctic. The cores come from very ice-rich, fine-grained sediments — similar to loess in our latitudes — that were deposited in large areas of Siberia and Alaska during the last ice age. The cores, up to 12 metres long, comprise sediments deposited over a period of up to 55,000 years.

The analyses of the permafrost cores show that a significant part (25-35 %) of the carbon is associated with the mineral particles and thus more difficult to access for microorganisms. “Predictions of interactions between thawing permafrost and climate are very complicated because the microbial degradability of the organic material in the sediments has varied greatly over the last 55,000 years. This is due to the different climatic conditions during this long period of deposition,” Janet Rethemeyer explained. Warmer and wetter conditions resulted in poorer binding of carbon to the mineral particles, while a colder and drier climate led to stronger binding, primarily to iron oxides. Stronger binding to iron oxides means that the decomposition rates of old plant material are lower, as Professor Dr. Michael Bonkowski from the Institute of Zoology, Department of Terrestrial Ecology at the University of Cologne has shown in laboratory experiments.

“These new findings can make a significant contribution to making computer models for forecasting greenhouse gas emissions from thawing permafrost more reliable,” said Jannik Martens, who is currently conducting research at Columbia University in New York.

A new study led by Dr. Natalie Johnson, associate professor in the Texas A&M University School of Public Health’s Department of Environmental and Occupational Health, shows that exposure to ultrafine particles (UFPs) during pregnancy enhances respiratory viral infection risk. The results of the study were published recently in Particle and Fibre Toxicology.

“We know that air pollution affects the pulmonary immune system, making individuals more susceptible to viral infections,” Johnson said. “We also know pregnant women are already at increased risk for severe flu. Surprisingly, studies have not interrogated the combined effects of pregnancy, air pollution and influenza. Our findings demonstrate the need to further study these interactions in order to prevent short and perhaps long-term impacts on maternal health.”

In the study, Johnson and her co-authors point out that there are several physiological characteristics that explain maternal susceptibility to viral infection. Among those are increased cardiac output and decreased tidal volume — the amount of air that moves in or out of the lungs with each respiratory cycle — as well as immunological changes such as selective modulation of immune cell subsets to protect the developing fetus.

The research team also highlights that vaccination compliance during pregnancy is generally below 50 percent, despite vaccination against influenza being safe and effective, leading to increased risk for developing respiratory infection.

As a result, air pollution, which is a worldwide environmental health issue, is responsible for one in nine deaths with an annual premature mortality of more than 7 million. A mixture of gases and tiny airborne particulate matter, which is categorized as UFPs, are critical to recognize and identify, especially to protect vulnerable populations.

The research team says these findings support future clinical and regulatory interventions for protecting pregnant women and controlling UFPs. According to the researchers, it is imperative that pregnant women in urban cities, where influenza and UFPs are more prevalent, are provided vaccinations and preventive measures limiting UFP exposure to protect maternal health.

“Air pollution is a pervasive environmental health issue,” Johnson said. “Strategies to protect the most vulnerable, like pregnant women, are of high priority to decrease adverse health effects.”

Additional authors include Nicholas L. Drury, Texas A&M Department of Environmental and Occupational Health and Texas A&M Department of Nutrition; Toriq Mustapha, Texas A&M Department of Environmental and Occupational Health; Ross A. Shore, Texas A&M Department of Environmental and Occupational Health, Jiayun Zhao, Texas A&M Department of Chemistry; Gus A. Wright, Texas A&M Department of Veterinary Pathobiology; Aline Rodrigues Hoffmann, University of Florida Department of Comparative, Diagnostic, and Population Medicine; Susanne U. Talcott, Texas A&M Department of Nutrition; Annette Regan, University of San Francisco School of Nursing and Health Professions; Robert M. Tighe, Duke University Department of Medicine; and Renyi Zhang, Texas A&M Department of Chemistry and Texas A&M Department of Atmospheric Sciences.

Grambank was constructed in an international collaboration between the Max Planck institutes in Leipzig and Nijmegen, the Australian National University, the University of Auckland, Harvard University, Yale University, the University of Turku, Kiel University, Uppsala University, SOAS, the Endangered Languages Documentation Programme, and over a hundred scholars from around the world. Grambank’s coverage spans 215 different language families and 101 isolates from all inhabited continents. “The design of the feature questionnaire initially required numerous revisions in order to encompass many of the diverse solutions that languages have evolved to code grammatical properties,” says Hedvig Skirgård, who coordinated much of the coding and is the lead author of the study.

Limits on variation

The team settled on 195 grammatical properties, ranging from word order to whether or not a language has gendered pronouns. For instance, many languages have separate pronouns for ‘he’ and ‘she’, but some also have male and female versions of ‘I’ or ‘you’. The possible ‘design space’ would be enormous if grammatical properties were to vary freely. Limits on variation could be related to cognitive principles rooted in memory or learning, rendering some grammatical structures more likely than others. Limits could also be related to historical ‘accidents’, such as descent from a common language or contact with other languages.

The researchers discovered much greater flexibility in the combination of grammatical features than many theorists have assumed. “Languages are free to vary considerably in quantifiable ways, but not without limits,” explains Stephen Levinson, Director emeritus of the Max Planck Institute for Psycholinguistics in Nijmegen and one of the founders of the Grambank project. “A sign of the extraordinary diversity of the 2400 languages in our sample is that only five of them occupy the same location in design space (share the same grammatical properties).”

Languages show much greater similarity to those with a common ancestor than those they are in contact with. “Genealogy generally trumps geography,” says Russell Gray, Director of the Department of Linguistic and Cultural Evolution and senior author of the study. “Nevertheless, if processes of linguistic evolution and diversification were run again from the beginning, there would still be some resemblance to what we now have. The constraints of human cognition mean that, while there is a great deal of historical contingency in the organisation of grammatical structures, there are regular patterns as well.”

Diversity under threat

“The extraordinary diversity of languages is one of humanity’s greatest cultural endowments,” concludes Levinson. “This endowment is under threat, especially in some areas such as Northern Australia, and parts of South and Northern America. Without sustained efforts to document and revitalise endangered languages, our linguistic window into human history, cognition and culture will be seriously fragmented.”

The Grambank database is an open-access comprehensive resource maintained by the Max Planck Society. “It puts linguistics on an even footing with genetics, archaeology and anthropology in terms of quantitative, large scale, accessible data,” says Gray. “I hope it will facilitate the exploration of links between linguistic diversity and a broad array of other cultural and biological traits, ranging from religious beliefs to economic behavior, musical traditions and genetic lineages. These links with other facets of human behavior will make Grambank a key resource not only in linguistics, but in the multidisciplinary endeavour of understanding human diversity.”

One of the first brain regions to show neurodegeneration in Alzheimer’s disease is a part of the hypothalamus called the mammillary body. In a new study, MIT researchers have identified a subset of neurons within this body that are most susceptible to neurodegeneration and hyperactivity. They also found that this damage leads to memory impairments.

The findings suggest that this region may contribute to some of the earliest symptoms of Alzheimer’s disease, making it a good target for potential new drugs to treat the disease, the researchers say.

“It is fascinating that only the lateral mammillary body neurons, not those in the medial mammillary body, become hyperactive and undergo neurodegeneration in Alzheimer’s disease,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the senior author of the study.

In a study of mice, the researchers showed that they could reverse memory impairments caused by hyperactivity and neurodegeneration in mammillary body neurons by treating them with a drug that is now used to treat epilepsy.

Former MIT postdoc Wen-Chin (Brian) Huang and MIT graduate students Zhuyu (Verna) Peng and Mitchell Murdock are the lead authors of the paper, which appears today in Science Translational Medicine.

Predisposed to degeneration

As Alzheimer’s disease progresses, neurodegeneration occurs along with the buildup of amyloid beta plaques and misfolded Tau proteins, which form tangles in the brain. One question that remains unresolved is whether this neurodegeneration strikes indiscriminately, or if certain types of neurons are more susceptible.

“If we could identify specific molecular properties of classes of neurons that are predisposed to dysfunction and degeneration, then we would have a better understanding of neurodegeneration,” Murdock says. “This is clinically important because we could find ways to therapeutically target these vulnerable populations and potentially delay the onset of cognitive decline.”

In a 2019 study using a mouse model of Alzheimer’s disease, Tsai, Huang, and others found that the mammillary bodies — a pair of structures found on the left and right underside of the hypothalamus — had the highest density of amyloid beta. These bodies are known to be involved in memory, but their exact role in normal memory and in Alzheimer’s disease is unknown.

To learn more about the mammillary body’s function, the researchers used single-cell RNA-sequencing, which can reveal the genes that are active within different types of cells in a tissue sample. Using this approach, the researchers identified two major populations of neurons: one in the medial mammillary body and the other in the lateral mammillary body. In the lateral neurons, genes related to synaptic activity were very highly expressed, and the researchers also found that these neurons had higher spiking rates than medial mammillary body neurons.

Based on those differences, the researchers wondered if the lateral neurons might be more susceptible to Alzheimer’s disease. To explore that question, they studied a mouse model with five genetic mutations linked to early-onset Alzheimer’s in humans. The researchers found that these mice showed much more hyperactivity in lateral mammillary body neurons than healthy mice. However, the medial mammillary body neurons in healthy mice and the Alzheimer’s model did not show any such differences.

The researchers found that this hyperactivity emerged very early — around two months of age (the equivalent of a young human adult), before amyloid plaques begin to develop. The lateral neurons became even more hyperactive as the mice aged, and these neurons were also more susceptible to neurodegeneration than the medial neurons.

“We think the hyperactivity is related to dysfunction in memory circuits and is also related to a cellular progression that might lead to neuronal death,” Murdock says.

The Alzheimer’s mouse model showed impairments in forming new memories, but when the researchers treated the mice with a drug that reduces neuronal hyperactivity, their performance on memory tasks was significantly improved. This drug, known as levetiracetam, is used to treat epileptic seizures and is also in clinical trials to treat epileptiform activity — hyperexcitability in the cortex, which increases the risk of seizures — in Alzheimer’s patients.

Comparing mice and humans

The researchers also studied human brain tissue from the Religious Orders Study/Memory and Aging Project (ROSMAP), a longitudinal study that has tracked memory, motor, and other age-related issues in older people since 1994. Using single-cell RNA-sequencing of mammillary body tissue from people with and without Alzheimer’s disease, the researchers found two clusters of neurons that correspond to the lateral and medial mammillary body neurons they found in mice.

Similar to the mouse studies, the researchers also found signatures of hyperactivity in the lateral mammillary bodies from Alzheimer’s tissue samples, including overexpression of genes that encode potassium and sodium channels. In those samples, they also found higher levels of neurodegeneration in the lateral neuron cluster, compared to the medial cluster.

Other studies of Alzheimer’s patients have found a loss of volume of the mammillary body early in the disease, along with deposition of plaques and altered synaptic structure. All of these findings suggest that the mammillary body could make a good target for potential drugs that could slow down the progression of Alzheimer’s disease, the researchers say.

Tsai’s lab is now working on further defining how the lateral neurons of the mammillary body are connected to other parts of the brain, to figure out how it forms memory circuits. The researchers also hope to learn more about what properties of the lateral neurons of the mammillary body make them more vulnerable to neurodegeneration and amyloid deposition.

The research was funded by the JBP Foundation, the Ludwig Family Foundation, and the U.S. National Institutes of Health.