Culture

TROY, N.Y. -- In a test of antiviral effectiveness against the virus that causes COVID-19, an extract from edible seaweeds substantially outperformed remdesivir, the current standard antiviral used to combat the disease. Heparin, a common blood thinner, and a heparin variant stripped of its anticoagulant properties, performed on par with remdesivir in inhibiting SARS-CoV-2 infection in mammalian cells.

Published online today in Cell Discovery, the research is the latest example of a decoy strategy researchers from the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselear Polytechnic Institute are developing against viruses like the novel coronavirus that spawned the current global health crisis.

The spike protein on the surface of SARS-CoV-2 latches onto the ACE-2 receptor, a molecule on the surface of human cells. Once secured, the virus inserts its own genetic material into the cell, hijacking the cellular machinery to produce replica viruses. But the virus could just as easily be persuaded to lock onto a decoy molecule that offers a similar fit. The neutralized virus would be trapped and eventually degrade naturally.

Previous research has shown this decoy technique works in trapping other viruses, including dengue, Zika, and influenza A. To hear the researchers discuss their findings, watch this video.

"We're learning how to block viral infection, and that is knowledge we are going to need if we want to rapidly confront pandemics," said Jonathan Dordick, the lead researcher and a professor of chemical and biological engineering at Rensselaer Polytechnic Institute. "The reality is that we don't have great antivirals. To protect ourselves against future pandemics, we are going to need an arsenal of approaches that we can quickly adapt to emerging viruses."

The Cell Discovery paper tests antiviral activity in three variants of heparin (heparin, trisulfated heparin, and a non-anticoagulant low molecular weight heparin) and two fucoidans (RPI-27 and RPI-28) extracted from seaweed. All five compounds are long chains of sugar molecules known as sulfated polysaccharides, a structural conformation that the results of a binding study published earlier this month in Antiviral Research suggested as an effective decoy.

The researchers performed a dose response study known as an EC50 -- shorthand for the effective concentration of the compound that inhibits 50% of viral infectivity -- with each of the five compounds on mammalian cells. For the results of an EC50, which are given in a molar concentration, a lower value signals a more potent compound.

RPI-27 yielded an EC50 value of approximately 83 nanomolar, while a similar previously published and independent in vitro test of remdesivir on the same mammalian cells yielded an EC50 of 770 nanomolar. Heparin yielded an EC50 of 2.1 micromolar, or about one-third as active as remdesivir, and a non-anticoagulant analog of heparin yielded an EC50 of 5.0 micromolar, about one-fifth as active as remdesivir.

A separate test found no cellular toxicity in any of the compounds, even at the highest concentrations tested.

"What interests us is a new way of getting at infection," said Robert Linhardt, a Rensselaer professor of chemistry and chemical biology who is collaborating with Dordick to develop the decoy strategy. "The current thinking is that the COVID-19 infection starts in the nose, and either of these substances could be the basis for a nasal spray. If you could simply treat the infection early, or even treat before you have the infection, you would have a way of blocking it before it enters the body."

Dordick added that compounds from seaweed "could serve as a basis for an oral delivery approach to address potential gastrointestinal infection."

In studying SARS-CoV-2 sequencing data, Dordick and Linhardt recognized several motifs on the structure of the spike protein that promised a fit compatible with heparin, a result borne out in the binding study. The spike protein is heavily encrusted in glycans, an adaptation that protects it from human enzymes which could degrade it, and prepares it to bind with a specific receptor on the cell surface.

"It's a very complicated mechanism that we quite frankly don't know all the details about, but we're getting more information," said Dordick. "One thing that's become clear with this study is that the larger the molecule, the better the fit. The more successful compounds are the larger sulfated polysaccharides that offer a greater number of sites on the molecules to trap the virus."

Molecular modeling based on the binding study revealed sites on the spike protein where the heparin was able to interact, raising the prospects for similar sulfated polysaccharides.

"This exciting research by Professors Dordick and Linhardt is among several ongoing research efforts at CBIS, as well as elsewhere at Rensselaer, to tackle the challenges of the COVID-19 pandemic through novel therapeutic approaches and the repurposing of existing drugs," said CBIS Director Deepak Vashishth.

Washington, DC - July 24, 2020 - A team of researchers showed that artificial intelligence (AI) could help predict the type of bacteria that caused the infection in patients with pneumonia. The research is presented at ASM Microbe Online, the annual meeting of the American Society for Microbiology.

"This research highlights the potential of AI as a supplementary tool for physicians in identifying causal pathogens of pneumonia, even before sputum culture results are available," said Joowhan Sung, M.D., hospitalist at MedStar Southern Maryland Hospital. "We demonstrated that physicians could be assisted by AI to decide appropriate antibiotics."

In the study, investigators showed that AI could use the information available in the emergency room and predict if the patient has MRSA or pseudomonas so that physicians can immediately prescribe specific antibiotics targeting specific bacteria.

Infection caused by antibiotic-resistant bacteria is difficult to treat and can be life-threatening. According to the CDC, "more than 2.8 million antibiotic-resistant infections occur, and more than 35,000 people die as a result".

Pneumonia caused by bacteria such as Methicillin-resistant Staphylococcus Aureus (MRSA) or pseudomonas can be fatal, as they are resistant to commonly prescribed antibiotics. Although there are effective antibiotics against these infections, the test, sputum culture, takes at least 48 hours to incubate and identify these bacteria from the sputum, while these patients might deteriorate within hours.

The investigators presented an analysis of more than 50,000 intensive care unit (ICU) admissions data from Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts. The researchers analyzed records of patients who were admitted with pneumonia and trained an AI, "neural network" agent using the dataset. The AI agent showed promising results in predicting bacteria that caused the infection.

"Similar techniques can be applied to future research on pneumonia amid the current pandemic, such as capturing bacterial co-infection in those with known COVID-19, which could be fatal if undetected," said Sung.

Jun Hyek Jang, M.S., senior researcher at AvoMD, Inc. and Joongheum Park, M.D., hospitalist at Beth Israel Deaconess Medical Center, also contributed to this work. This research received no external funding.

ASM Microbe Online brings you the dynamic, cutting-edge science of ASM Microbe 2020, the annual meeting of the American Society for Microbiology. Explore the latest research in the microbial sciences with ePosters, hear from experts in the field during live keynotes and access track-related content with a curated selection of on-demand sessions.

The United States should prepare for a triumphant or ascending People's Republic of China - scenarios that not only align with current PRC national development trends but also represent the most challenging future scenarios for the U.S. military, according to a new RAND Corporation report that examines China's grand strategy out to 2050.

The authors make the case that the kind of country China becomes, and the way that its military evolves, is neither foreordained nor completely beyond the influence of the United States or U.S. military. However, Beijing's intense preoccupation with internal security and deep suspicions regarding U.S. intentions toward China may frustrate attempts by Washington to improve bilateral relations and encourage more liberal domestic policies.

"The experience of COVID-19 is a prime example," said Andrew Scobell, the study's lead author and a senior political scientist at RAND, a nonprofit, nonpartisan research organization. "Beijing's secretive approach to the pandemic has exacerbated tensions with a wide array of other countries, including the United States, and contributed to economic dislocation (aka 'decoupling') between China and some of its key trading partners. While Beijing seems to have been effective in dealing with the pandemic at home, this has been accomplished through draconian and repressive measures."

To map out potential future scenarios - What will China, and its military, look like in 2050? What will U.S.-China relations look like in 2050? - researchers studied trends in the management of politics and society and analyzed the specific national-level strategies and plans that China's Communist Party rulers have put in place to further their vision of a China that is well governed, socially stable, economically prosperous, technologically advanced, and militarily powerful by 2049, the centenary of the founding of the PRC.

The report describes four possible scenarios for China at mid-century - triumphant, ascendant, stagnant and imploding - with the middle two most likely. If China proves ascendant, the U.S. military should anticipate increased risk to already threatened forward-based forces in Japan, South Korea, and the Philippines, as well as a loss of the ability to operate routinely in the air and sea space above and in the Western Pacific.

The report recommends that the U.S Army be prepared for a China whose role on the Asia-Pacific and global stages grows steadily. To prepare for military conflict in such circumstances, the U.S. Army should optimize its abilities to deter hostilities, get troops and equipment to hotspots quickly, operate from forward bases, and work with allied forces.

The U.S. could field more robust cyber and network attack capabilities and other means to counter China's unmanned aircraft systems, the authors assert. The capacity to respond quickly and effectively to China's burgeoning reconnaissance-strike system will play an important role in determining the extent to which China's leadership remains risk averse when considering military options to resolve regional disputes.

The report, conducted for the U.S. Army, is based on a review of Chinese and Western literature on the PRC's long-term strategic development and security plans and objectives, official statements by high-level Chinese officials and institutions, speeches by paramount leaders, white papers published by the Ministry of National Defense and other PRC government agencies, authoritative People's Liberation Army (PLA) texts, as well as Western and other non-Chinese analyses of these documents.

A Nature study authored by a global team of scientists and led by Sumit Chanda, Ph.D., professor at Sanford Burnham Prebys Medical Discovery Institute, has identified 21 existing drugs that stop the replication of SARS-CoV-2, the virus that causes COVID-19.

The scientists analyzed one of the world’s largest collections of known drugs for their ability to block the replication of SARS-CoV-2, and reported 100 molecules with confirmed antiviral activity in laboratory tests. Of these, 21 drugs were determined to be effective at concentrations that could be safely achieved in patients. Notably, four of these compounds were found to work synergistically with remdesivir, a current standard-of-care treatment for COVID-19.

“Remdesivir has proven successful at shortening the recovery time for patients in the hospital, but the drug doesn’t work for everyone who receives it. That’s not good enough,” says Chanda, director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and senior author of the study. "As infection rates continue to rise in America and around the world, the urgency remains to find affordable, effective, and readily available drugs that can complement the use of remdesivir, as well as drugs that could be given prophylactically or at the first sign of infection on an outpatient basis."

Extensive testing conducted

In the study, the research team performed extensive testing and validation studies, including evaluating the drugs on human lung biopsies that were infected with the virus, evaluating the drugs for synergies with remdesivir, and establishing dose-response relationships between the drugs and antiviral activity.

Of the 21 drugs that were effective at blocking viral replication, the scientists found:

13 have previously entered clinical trials for other indications and are effective at concentrations, or doses, that could potentially be safely achieved in COVID-19 patients.

Two are already FDA approved: astemizole (allergies), clofazamine (leprosy), and remdesivir has received Emergency Use Authorization from the agency (COVID-19).

Four worked synergistically with remdesivir, including the chloroquine derivative hanfangchin A (tetrandrine), an antimalarial drug that has reached Phase 3 clinical trials.

"This study significantly expands the possible therapeutic options for COVID-19 patients, especially since many of the molecules already have clinical safety data in humans," says Chanda. "This report provides the scientific community with a larger arsenal of potential weapons that may help bring the ongoing global pandemic to heel."

The researchers are currently testing all 21 compounds in small animal models and "mini lungs," or lung organoids, that mimic human tissue. If these studies are favorable, the team will approach the U.S. Food and Drug Administration (FDA) to discuss a clinical trial(s) evaluating the drugs as treatments for COVID-19.

"Based on our current analysis, clofazimine, hanfangchin A, apilimod and ONO 5334 represent the best near-term options for an effective COVID-19 treatment," says Chanda. "While some of these drugs are currently in clinical trials for COVID-19, we believe it's important to pursue additional drug candidates so we have multiple therapeutic options if SARS-CoV-2 becomes drug resistant."

Screening one of the world's largest drug libraries

The drugs were first identified by high-throughput screening of more than 12,000 drugs from the ReFRAME drug repurposing collection—the most comprehensive drug repurposing collection of compounds that have been approved by the FDA for other diseases or that have been tested extensively for human safety.

Arnab Chatterjee, Ph.D., vice president of medicinal chemistry at Calibr and co-author on the paper, says ReFRAME was established to tackle areas of urgent unmet medical need, especially neglected tropical diseases. “We realized early in the COVID-19 pandemic that ReFRAME would be an invaluable resource for screening for drugs to repurpose against the novel coronavirus,” says Chatterjee.

The drug screen was completed as rapidly as possible due to Chanda’s partnership with the scientist who discovered the first SARS virus, Kwok-Yung Yuen, M.D., chair of Infectious Diseases at the University of Hong Kong; and Shuofeng Yuan, Ph.D., assistant research professor in the Department of Microbiology at the University of Hong Kong, who had access to the SARS-CoV-2 virus in February 2020.

NEW YORK, NY (July 24, 2020) -- The number of heart transplants in the United States declined sharply during the beginning of the pandemic, even in areas of the country with few COVID-19 cases at the time, according to an analysis by researchers at Columbia University Irving Medical Center.

The study found that the number of heart transplants performed nationwide dropped 26% during the 8-week period marking the height of the pandemic in the Northeast compared to the prior 8 weeks. The drop in transplants was similar across regions and occurred even in areas with lower infection rates.

The study was published in JAMA Cardiology.

"We had concerns that the availability of ICU beds and ventilators would impact our transplant patients, particularly in the Northeast," says Ersilia DeFilippis, MD, a postdoctoral clinical fellow in medicine and cardiology at Columbia University Vagelos College of Physicians and Surgeons and the first author of the paper.

"But we were surprised to see a decline in heart transplants in other parts of the country, where there were far fewer COVID-19 cases at that time. Our data show that this pandemic has had far-reaching impacts on the care our patients with advanced heart failure are receiving."

Heart Transplant Patients Require Many Hospital Resources

Heart transplant patients require a lot of hospital resources, DeFilippis says. "Many patients are sick enough to require hospitalization prior to transplant, often in an intensive care unit, sometimes for weeks or months. Some of these patients are supported on temporary machines to help their hearts pump blood to the body. In addition, the transplant surgery itself requires a ventilator, blood products, and significant personnel. Patients then require intensive care unit monitoring in the immediate post-transplant period."

At the beginning of the pandemic, clinicians had to weigh the risks of exposing medically fragile patients with heart failure, though well enough to remain at home, to SARS-CoV-2 infection with the risks of delaying a life-changing surgery.

DeFilippis and her colleagues found that many clinicians reacted by taking their patients off the waitlist -- a measure typically pursued when a patient encounters a health issue that temporarily or permanently disqualifies them for transplantation but was expanded during the pandemic to include patients at risk of SARS-CoV-2 infection and to accommodate transplant centers that deferred acceptance of donor organs due to the pandemic.

They found that waitlist inactivations increased 75% during the pandemic, driven largely by the Northeast. At the same time, 37% fewer people were placed on heart transplant waitlists during the pandemic, with the most significant decreases occurring in the Northeast, the Great Lakes region, and the Southwest.

In addition, the researchers found that the availability of donor hearts decreased by 26% during the COVID-19 period compared with the pre-COVID-19 period.

"It is possible that limited access to testing for donors as well as restrictions on organ procurement organizations may have contributed to the decrease we observed in donor recovery," says DeFilippis.

Next, the researchers plan to study the impact of these changes on patient survival while on the transplant waitlist and post-transplant survival.

"It will be similarly important to determine how the pandemic has affected the timing of transplant evaluations and changes in left ventricular assist device implantation. As the pandemic continues, we must be mindful of the effects of these delays on our patients," says DeFilippis.

University of Rochester researchers are setting a new standard when it comes to producing ultrafast laser pulses over a broader range of wavelengths than traditional laser sources.

In work published in Physical Review Letters, William Renninger, an assistant professor of optics, along with members of his lab, describe a new device, called the "stretched-pulse soliton Kerr resonator," that enhances the performance of ultrafast laser pulses. The work has important implications for a range of engineering and biomedical applications, including spectroscopy, frequency synthesis, distance ranging, pulse generation, and others.

The device creates an ultrafast laser pulse--on the order of femtoseconds, or one quadrillionth of a second--that's freed from the physical limits endemic to sources of laser light--what laser scientists call laser gain--and the limits of the sources' wavelengths.

"Simply put, this is the shortest pulse ever from a gain-free fiber source," Renninger says.

Renninger and his team of graduate research and postdoctoral associates improved upon Kerr resonators, an exciting new alternative for generating femtosecond laser pulses that have been the subject of considerable research.

The lab overcame a challenge to pulse duration in other versions of Kerr resonators by discovering a new soliton--a short burst or localized envelope of a wave--that maintains its shape while propagating at a constant velocity. The solitons generated in Renninger's device differ from the solitons in other Kerr resonators, specifically in the shape and behavior of the stretching pulses they create.

"It is stable in the sense it keeps repeating the same thing over and over, getting longer, then shorter, longer then shorter," Renninger says.

The pulses "feature a broad spectral bandwidth and a compressed pulse duration of 210 femtoseconds, which is the shortest pulse duration observed to date from fiber Kerr resonators," the researchers state in the paper.

Lead author Xue Dong is a graduate research associate in the Renninger lab. In addition to Renninger, other coauthors are Qian Yang and Christopher Spiess, also graduate research associates in the lab, and Victor Bucklew, a former postdoctoral associate in the lab.

The study was funded by in part by the University's Technology Development Fund, a University Research Award, and by the National Institutes of Health. A patent is pending. Interested parties can contact Curtis Broadbent, licensing manager at URVentures, about licensing the technology.

Making ultrafast lasers more accessible

Renninger, an expert in creating sources for femtosecond lasers, received his BS and PhD degrees in applied physics from Cornell University. Before joining the Institute of Optics, he was a postdoctoral associate and an associate research scientist in the Department of Applied Physics at Yale University.

He recently received a National Science Foundation CAREER award, which includes funding to create open source access to information for designing and creating advanced lasers sources generating femtosecond pulses.

"There are now commercial products, but they're very expensive. They are prohibitive for many research groups with limited budgets for equipment," Renninger says.

Much of the cost is for expertise, not components, so his group will use part of the CAREER funding to provide consulting for research groups at smaller universities in how to design and build femtosecond lasers for basic research.

"The ultimate goal is to have a design guide published on our website for everybody," Renninger says.

URBANA, Ill. - With more ethanol in production and a greater ability to upcycle co-products into animal feed ingredients, companies are creating custom products and partnering with University of Illinois researchers to test for quality and digestibility.

In a recent study published in the Journal of Animal Science, Illinois researchers show a new high-protein distillers dried grains with solubles (DDGS) product from Marquis Energy has greater energy and protein digestibility than conventional DDGS.

"We've never seen a corn co-product with such a high energy concentration or amino acid digestibility," says Hans H. Stein, professor in the Department of Animal Sciences at Illinois and co-author on the study. "It's clearly a high-value product."

The product, branded ProCap DDGS, contains 48% crude protein, far higher than conventional de-oiled DDGS, which the research team evaluated at 31% in a nutrient analysis of each ingredient. ProCap DDGS also provided approximately 1,200 kcal per kilogram of metabolizable energy more than conventional DDGS, according to the analysis.

The study consisted of three experiments. In the first, the researchers evaluated the apparent and standardized ileal digestibility of crude protein and amino acids in three diets: ProCap DDGS, conventional de-oiled DDGS (also from Marquis Energy), and a nitrogen-free diet used to determine endogenous losses of amino acids and crude protein. Vitamins and minerals were added to each diet to meet or exceed dietary requirements. The researchers fed each diet to nine growing pigs for six days at three times the maintenance energy requirement.

On the fifth and sixth days, researchers collected ileal digesta and analyzed dry matter, crude protein, and amino acids. As suggested by their nutrient analysis of the raw products, the researchers found the ProCap DDGS contained more crude protein and amino acids than de-oiled DDGS, and the standardized ileal digestibility of nearly all amino acids was greater in ProCap DDGS.

The second experiment focused on energy digestibility. In this case, the researchers evaluated three diets: corn, corn + ProCap DDGS, and corn + de-oiled DDGS. Again, all diets were supplemented with vitamins and minerals as needed. The team fed each diet to 24 growing barrows for 13 days at 3.2 times the maintenance energy requirement. Researchers calculated digestible energy and metabolizable energy values for all diets by collecting feces and urine over a four-day period during the experiment.

"If you look at the energy, which is of very high value for producers, and you compare with corn, we had much greater energy concentration in the ProCap DDGS, whereas conventional DDGS was lower than corn," Stein says.

The third experiment evaluated phosphorous digestibility. Researchers fed 32 barrows ProCap DDGS and de-oiled DDGS with or without microbial phytase. The pigs consumed these diets, along with supplemental vitamins and minerals (except phosphorus and calcium), for 13 days. Researchers collected feces from day six to day 12, and found that phytase + ProCap DDGS increased the digestibility of phosphorus. However, without phytase, phosphorus digestibility of ProCap DDGS was lower than de-oiled DDGS.

The three experiments confirm ProCap DDGS has greater amino acid digestibility and contains more metabolizable energy than de-oiled DDGS, but has reduced phosphorus digestibility.

"The ethanol industry is clearly moving toward trying to separate the different streams that come out after fermentation so they can identify high-value, high-quality products. I think we'll see even more innovation and new feed ingredients in the future thanks to more advanced technologies in ethanol plants," Stein says.

Have you ever wondered why our hands have five fingers? And what about amphibians? They usually only have four. Until now it was assumed that this was already the case with the early ancestors of today's frogs and salamanders, the Temnospondyli. However, a new find of the crocodile-like Temnospondyl Metoposaurus krasiejowensis from the late Triassic (about 225 million years old) in Poland shows five metacarpal bones and thus five fingers. As the researchers from the Universities of Bonn and Opole (Poland) note, this finding is very important, because until now, fossil animal tracks may have been wrongly assigned. The results have now been published in the Journal of Anatomy.

Modern amphibians usually have four fingers on the forelimb (and never more), which is called a "four-rayed hand", as opposed to our five-rayed hand. Of all groups of terrestrial vertebrates, amphibians show the greatest variation in the number of frontfingers Reptiles are the most conservative and usually have five. In birds, the finger bones in the wing have been lost completely. In mammals, the number of toes in the forelimb also varies greatly: Primates and raccoons have five, in horses only the third has survived, while in cattle and other even-toed ungulates fingers three and four remain. What they all have in common, however, is that this loss of toes or fingers originates from a five-ray pattern, which is why amphibians cannot be the ancestors of all these terrestrial vertebrate groups.

Exact number of toes is controversial

It has been known for some time that the earliest quadrupeds had significantly more fingers than five, such as Acanthostega, which had eight in the forelimb, or Ichthyostega with seven in the hind foot. As early as 300 million years ago, all but the five-fingered forms became extinct. The five-ray pattern was then retained in the real land animals, but was reduced again and again (see horses). The ancestors of today's amphibians, the Temnospondyli, presented contradictory evidence of skeletons with four fingers, but also tracks that had five.

Temnospondyli is an important group of the early, very diverse quadrupeds. Some temnospondyls became as big as crocodiles, others were rather small. However, like all amphibians, they were dependent on water during their larval stage. Their most famous representatives include Eryops or Mastodonsaurus. "It's also important to understand the evolution of modern amphibians, as this group probably evolved from the Temnospondyli," says Dr. Dorota Konietzko-Meier from the Institute for Geosciences at the University of Bonn, who discovered and prepared the left forelimb of a Metoposaurus krasiejowensis in Krasiejów (southwest Poland).

However, despite the long history of research, the exact number of fingers in Metoposaurus and other temnospondyls is still controversial. "It's remarkable that even in the case of the very well-researched Eryops, the skeletal reconstruction exhibited at the Muséum National d'Histoire Naturelle in Paris has five fingers, while only four fingers can be seen at the National Museum of Natural History in Washington," says Ella Teschner, a doctoral student from Bonn and Opole. Lately, science has assumed that, similar to most modern amphibians, all Temnospondyli have only four toes in their forelimbs. This resulted in the five-toed footprints common in the Permian and Triassic periods being almost automatically assumed to not belong to Temnospondyli.

"The find from the famous Upper Triassic site Krasiejów in Poland therefore offers a new opportunity to study the architecture and development of the hand of the early quadrupeds," says paleontologist Prof. Dr. Martin Sander from the University of Bonn. A considerably broader view of the entire group of Temnospondyli did not show a clear trend with regard to the five-ray pattern and suggested that the number of digits was not as limited in the phylogenetic context as was assumed. "Evidently, the temnospondyls were already experimenting with the four-ray pattern, and the five-ray pattern died out before the emergence of modern amphibians," adds Sander.

Five fingers on each hand?

"Even if the ossification of five metacarpal bones described here was only a pathology, it still shows that a five-ray pattern was possible in Temnospondyli," says Konietzko-Meier. However, it could not be assumed with certainty that the reduction in the number of fingers/digits from five to four always affected the fifth place on the hand in these fossil taxa. The possibility that some of the four-fingered taxa were caused by the loss of the first ray cannot be excluded. Sander: "The new finding of a five-fingered hand is particularly important for the interpretation of tracks, as it shows that a five-fingered forefoot print could also belong to the Temnospondyli and thus indicate a considerably wider distribution area of these animals."

These results are also of general importance, since limb development plays an important role in evolutionary biology and medicine, and fossils may therefore provide important information for the evaluation of theories of hand development.

Proteins are essential to the life of cells, carrying out complex tasks and catalyzing chemical reactions. Scientists and engineers have long sought to harness this power by designing artificial proteins that can perform new tasks, like treat disease, capture carbon, or harvest energy, but many of the processes designed to create such proteins are slow and complex, with a high failure rate.

In a breakthrough that could have implications across the healthcare, agriculture, and energy sectors, a team lead by researchers in the Pritzker School of Molecular Engineering (PME) at the University of Chicago has developed an artificial intelligence-led process that uses big data to design new proteins.

By developing machine-learning models that can review protein information culled from genome databases, the researchers found relatively simple design rules for building artificial proteins. When the team constructed these artificial proteins in the lab, they found that they performed chemistries so well that they rivaled those found in nature.

"We have all wondered how a simple process like evolution can lead to such a high-performance material as a protein," said Rama Ranganathan, Joseph Regenstein Professor in the Department of Biochemistry and Molecular Biology, Pritzker Molecular Engineering, and the College. "We found that genome data contains enormous amounts of information about the basic rules of protein structure and function, and now we've been able to bottle nature's rules to create proteins ourselves."

The results were published July 24 in the journal Science.

Using artificial intelligence to learn design rules

Proteins are made up of hundreds or thousands of amino acids, and these amino acid sequences specify the protein's structure and function. But understanding just how to build these sequences to create novel proteins has been challenging. Past work has resulted in methods that can specify structure, but function has been more elusive.

What Ranganathan and his collaborators realized over the past 15 years is that genome databases--which are growing exponentially--contain enormous amounts of information about the basic rules of protein structure and function. His group developed mathematical models based on this data and then began using machine-learning methods to reveal new information about proteins' basic design rules.

For this research, they studied the chorismate mutase family of metabolic enzymes, a type of protein that is important for life in many bacteria, fungi, and plants. Using machine-learning models, the researchers were able to reveal the simple design rules behind these proteins.

The model shows that just conservation at amino acid positions and correlations in the evolution of pairs of amino acids are sufficient to predict new artificial sequences that would have the properties of the protein family.

"We generally assume that to build something, you have to first deeply understand how it works," Ranganathan said. "But if you have enough data examples, you can use deep learning methods to learn the rules of design, even as you are understanding how it works or why it's built that way."

He and his collaborators then created synthetic genes to encode for the proteins, cloned them into bacteria, and watched as the bacteria then made the synthetic proteins using their normal cellular machinery. They found that the artificial proteins had the same catalytic function as the natural chorismate mutase proteins.

A platform to understand other complex systems

Because the design rules are so relatively simple, the number of artificial proteins that researchers could potentially create with them is extremely large.

"The constraints are much smaller than we ever imagined they would be," Ranganathan said. "There is a simplicity in nature's design rules, and we believe similar approaches could help us search for models for design in other complex systems in biology, like ecosystems or the brain."

Though artificial intelligence revealed the design rules, Ranganathan and his collaborators still don't fully understand why the models work. Next they will work to understand just how the models came to this conclusion. "There is much more work to be done," he said.

In the meantime, they also hope to use this platform to develop proteins that can address pressing societal problems, like climate change. Ranganathan and Assoc. Prof. Andrew Ferguson have founded a company called Evozyne that will commercialize this technology with applications in energy, environment, catalysis, and agriculture. Ranganathan has worked with UChicago's Polsky Center for Entrepreneurship and Innovation to file patents and license the IP to the company.

"This system gives us a platform for rationally engineering protein molecules in a way that we always dreamed we could," he said. "Not only can it teach us the physics of how proteins work and how they evolve, it can help us find solutions for issues like carbon capture and energy harvesting. Even more generally, the studies in proteins might even help teach us how the deep neural networks behind modern machine learning actually work."

HANOVER, N.H. - July 24, 2020 - Researchers at Dartmouth, in collaboration with industry partners, have developed software techniques that make lighting in computer-generated images look more realistic. The research will be presented at the upcoming ACM SIGGRAPH conference, the premier venue for research in computer graphics.

The new techniques focus on "real time" graphics which need to maintain the illusion of interactivity as scenes change in response to user moves. These graphics can be used in applications such as video games, extended reality, and scientific visualization tools.

Both papers demonstrate how developers can create sophisticated lighting effects by adapting a popular rendering technique known as ray tracing.

"Over the last decade, ray tracing has dramatically increased the realism and visual richness of computer-generated images in movies where producing just a single frame can take hours," said Wojciech Jarosz, an associate professor of computer science at Dartmouth who served as the senior researcher for both projects. "Our papers describe two very different approaches for bringing realistic ray-traced lighting to the constraints of real time graphics."

The first project, developed with NVIDIA, envisions the possibilities for future games once developers incorporate NVIDIA's hardware-accelerated RTX ray tracing platform. Recent games have started to use RTX for physically correct shadows and reflections, but quality and complexity of lighting is currently limited by the small number of rays that can be traced per frame.

The new technique, called reservoir-based spatiotemporal importance resampling (ReSTIR), creates realistic lighting and shadows from millions of artificial light sources. The ReSTIR approach dramatically increases the quality of rendering on a computer's graphics card by reusing rays that were traced in neighboring pixels and in prior frames.

The new technique can be integrated into the design of future games and works up to 65 times faster than previous rendering techniques.

"This technology is not just exciting for what it can bring to real-time applications like games, but also its impact in the movie industry and beyond," said Benedikt Bitterli, a PhD student at Dartmouth who served as the first author of a research paper on the technique.

The second project, conducted in collaboration with Activision, describes how the video game publisher has incorporated increasingly realistic lighting effects into its games.

Traditionally, video games create lighting sequences in real time using what are called "baked" solutions: the complex ray-traced illumination is computed only once through a time-consuming process. The lighting created using this technique can be displayed easily during gameplay, but it is constrained to assuming a fixed configuration for a scene. As a result, the lighting cannot easily react to the movement of characters and cameras.

The research paper describes how Activision gradually evolved its "UberBake" system from the static approach to one which can depict subtle lighting changes in response to player interactions, such as turning lights on and off, or opening and closing doors.

Since UberBake was developed over many years to work on current games, it needed to work on a variety of existing hardware, ranging from high-end PCs to previous-generation gaming consoles.

"Video games are used by millions of people around the world," said Dario Seyb, a PhD student at Dartmouth who served as the research paper's co-first author. "With so many people interacting with video games, this technology can have a huge impact."

Dartmouth researchers on both projects are affiliated with the Dartmouth Visual Computing Lab.

"These industry collaborations have been fantastic. They allow our students to work on foundational academic research informed by practical problems in industry, allowing the work to have a more immediate, real-world impact," said Jarosz.

The research papers will be published in ACM Transactions on Graphics and presented at SIGGRAPH 2020 taking place online during the summer.

At a glance:

Loss of smell is the main neurological symptom of COVID-19, but the underlying mechanism has been unclear

New study shows infection of nonneuronal supporting cells in the nose and forebrain may be responsible for loss of smell in patients with COVID-19

Findings suggest olfactory sensory neurons are not vulnerable to SARS-CoV-2 infection because they do not express ACE2, a key protein that the virus uses to enter human cells

Results inform efforts to better understand COVID-19-related loss of smell

Temporary loss of smell, or anosmia, is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. Studies suggest it better predicts the disease than other well-known symptoms such as fever and cough, but the underlying mechanisms for loss of smell in patients with COVID-19 have been unclear.

Now, an international team of researchers led by neuroscientists at Harvard Medical School has identified the olfactory cell types most vulnerable to infection by SARS-CoV-2, the virus that causes COVID-19.

Surprisingly, sensory neurons that detect and transmit the sense of smell to the brain are not among the vulnerable cell types.

Reporting in Science Advances on July 24, the research team found that olfactory sensory neurons do not express the gene that encodes the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. Instead, ACE2 is expressed in cells that provide metabolic and structural support to olfactory sensory neurons, as well as certain populations of stem cells and blood vessel cells.

The findings suggest that infection of nonneuronal cell types may be responsible for anosmia in COVID-19 patients and help inform efforts to better understand the progression of the disease.

"Our findings indicate that the novel coronavirus changes the sense of smell in patients not by directly infecting neurons but by affecting the function of supporting cells," said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.

This implies that in most cases, SARS-CoV-2 infection is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia, Datta added, a condition that is associated with a variety of mental and social health issues, particularly depression and anxiety.

"I think it's good news, because once the infection clears, olfactory neurons don't appear to need to be replaced or rebuilt from scratch," he said. "But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."

A majority of COVID-19 patients experience some level of anosmia, most often temporary, according to emerging data. Analyses of electronic health records indicate that COVID-19 patients are 27 times more likely to have smell loss but are only around 2.2 to 2.6 times more likely to have fever, cough or respiratory difficulty, compared to patients without COVID-19.

Some studies have hinted that anosmia in COVID-19 differs from anosmia caused by other viral infections, including by other coronaviruses.

For example, COVID-19 patients typically recover their sense of smell over the course of weeks--much faster than the months it can take to recover from anosmia caused by a subset of viral infections known to directly damage olfactory sensory neurons. In addition, many viruses cause temporary loss of smell by triggering upper respiratory issues such as stuffy nose. Some COVID-19 patients, however, experience anosmia without any nasal obstruction.

Pinpointing vulnerability

In the current study, Datta and colleagues set out to better understand how sense of smell is altered in COVID-19 patients by pinpointing cell types most vulnerable to SARS-CoV-2 infection.

They began by analyzing existing single-cell sequencing datasets that in total catalogued the genes expressed by hundreds of thousands of individual cells in the upper nasal cavities of humans, mice and nonhuman primates.

The team focused on the gene ACE2, widely found in cells of the human respiratory tract, which encodes the main receptor protein that SARS-CoV-2 targets to gain entry into human cells. They also looked at another gene, TMPRSS2, which encodes an enzyme thought to be important for SARS-CoV-2 entry into the cell.

The analyses revealed that both ACE2 and TMPRSS2 are expressed by cells in the olfactory epithelium--a specialized tissue in the roof of the nasal cavity responsible for odor detection that houses olfactory sensory neurons and a variety of supporting cells.

Neither gene, however, was expressed by olfactory sensory neurons. By contrast, these neurons did express genes associated with the ability of other coronaviruses to enter cells.

The researchers found that two specific cell types in the olfactory epithelium expressed ACE2 at similar levels to what has been observed in cells of the lower respiratory tract, the most common targets of SARS-CoV-2, suggesting a vulnerability to infection.

These included sustentacular cells, which wrap around sensory neurons and are thought to provide structural and metabolic support, and basal cells, which act as stem cells that regenerate the olfactory epithelium after damage. The presence of proteins encoded by both genes in these cells was confirmed by immunostaining.

In additional experiments, the researchers found that olfactory epithelium stem cells expressed ACE2 protein at higher levels after artificially induced damage, compared with resting stem cells. This may suggest additional SARS-CoV-2 vulnerability, but it remains unclear whether or how this is important to the clinical course of anosmia in patients with COVID-19, the authors said.

Datta and colleagues also analyzed gene expression in nearly 50,000 individual cells in the mouse olfactory bulb, the structure in the forebrain that receives signals from olfactory sensory neurons and is responsible for initial odor processing.

Neurons in the olfactory bulb did not express ACE2. The gene and associated protein were present only in blood vessel cells, particularly pericytes, which are involved in blood pressure regulation, blood-brain barrier maintenance and inflammatory responses. No cell types in the olfactory bulb expressed the TMPRSS2 gene.

Smell loss clue

Together, these data suggest that COVID-19-related anosmia may arise from a temporary loss of function of supporting cells in the olfactory epithelium, which indirectly causes changes to olfactory sensory neurons, the authors said.

"We don't fully understand what those changes are yet, however," Datta said. "Sustentacular cells have largely been ignored, and it looks like we need to pay attention to them, similar to how we have a growing appreciation of the critical role that glial cells play in the brain."

The findings also offer intriguing clues into COVID-19-associated neurological issues. The observations are consistent with hypotheses that SARS-CoV-2 does not directly infect neurons but may instead interfere with brain function by affecting vascular cells in the nervous system, the authors said. This requires further investigation to verify, they added.

The study results now help accelerate efforts to better understand smell loss in patients with COVID-19, which could in turn lead to treatments for anosmia and the development of improved smell-based diagnostics for the disease.

"Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it's persistent," Datta said. "It can have serious psychological consequences and could be a major public health problem if we have a growing population with permanent loss of smell."

The team also hope the data can help pave inroads for questions on disease progression such as whether the nose acts as a reservoir for SARS-CoV-2. Such efforts will require studies in facilities that allow experiments with live coronavirus and analyses of human autopsy data, the authors said, which are still difficult to come by. However, the collaborative spirit of pandemic-era scientific research calls for optimism.

"We initiated this work because my lab had a couple of datasets ready to analyze when the pandemic hit, and we published an initial preprint," Datta said. "What happened after that was amazing, researchers across the globe offered to share and merge their data with us in a kind of impromptu global consortium. This was a real collaborative achievement."

A new study of human olfactory cells has revealed that viral invasion of supportive cells in the nasal cavity might be driving the loss of smell seen in some patients with COVID-19. The findings show that non-neuronal cells in the brain and nose express genes critical for SARS-CoV-2 entry, while neurons do not; therefore, non-neuronal cells are likely to be the primary targets for virus-induced damage leading to loss of smell, or anosmia. Recent investigations into COVID-19-associated anosmia showed that cells from the human upper airway express high levels of receptor genes involved in SARS-CoV-2 entry, suggesting that these respiratory epithelial cells serve as viral reservoirs during CoV-2 infection. However, these studies did not investigate the sheet of cells that line the nasal cavity, called the olfactory epithelium - the first entryway for pathogens before they reach the respiratory epithelium. Using bulk RNA sequencing of human cells from the nasal mucosa, David Brann and colleagues identified cell types in the olfactory epithelium in the nose and the brain's olfactory bulb that express two key receptor genes involved in SARS-CoV-2 entry, ACE2 and TMPRSS2. Single cell RNA sequencing of these cells and neurons provided the key insight that neither gene was detected in olfactory neurons, but both were highly expressed by support cells, stem cells, and perivascular cells in the nose and brain. Fluorescent staining of ACE2 in olfactory cells in mice confirmed this result and revealed pervasive expression of ACE2 protein in structural support cells of the nose and in cells that wrap around the capillaries of the olfactory bulb. Identifying the mechanisms that underlie the olfactory symptoms of COVID-19 can help lead to new diagnostics for SARS-CoV-2 infection, yield insights into the cellular dynamics of the nose, and propel future treatments for anosmia, the authors say.

A new study found raised levels of transforming growth factor beta-induced protein (TGFBIp) in blood sampled from roughly 100 people hospitalized for COVID-19, and further found that elevated levels of both the normal and acetylated forms of TGFBIp correlated with the severity of disease symptoms in these patients. While more work will be required to determine whether heightened levels of acetylated TGFBIp can serve as an exclusive, specific, and reliable diagnostic indicator for the severity of COVID-19, the research also suggests that TGFBIp could be a viable therapeutic target to treat severe inflammation - including deadly "cytokine storms" - in patients suffering from severe cases of the disease. While much work has been done to characterize the immune responses of patients with COVID-19, the inflammatory markers and cytokines known to be induced by SARS-CoV-2 infection are often short-lived. Hee Ho Park and colleagues set out to investigate whether increased levels of both the normal and acetylated forms of TGFBIp, a more stable molecule known to activate the immune-regulating transcription factor NF-κB, might serve as a more lasting signal of SARS-CoV-2 infection. The researchers analyzed blood samples from healthy controls and two cohorts of COVID-19 patients: those admitted to a hospital for treatment with relatively mild symptoms, and those who required ICU care to treat acute respiratory distress syndrome (ARDS) and/or sepsis. Compared with the healthy controls, both patient cohorts exhibited elevated levels of TGFBIp, as well as higher levels of acetylated TGFBIp, with the ICU patients exhibiting even greater levels of both protein forms. Upon treating immune cells taken from these patients with antibodies that neutralize TGFBIp, the researchers also observed a decrease in the production of inflammatory cytokines. While further work will be required to validate these results and assess the safety of the neutralizing antibodies, the finding nonetheless suggests that TGFBIp could be targeted to help treat severe inflammation in COVID-19 patients.

Current observations suggest that the coronavirus SARS-CoV-2 causes severe symptoms mainly in elderly patients with chronic disease. However when two pairs of previously healthy young brothers from two families required mechanical ventilation at the intensive care unit in rapid succession, doctors and researchers at Radboud University Medical Center were inclined to consider that genetic factors had a key role in compromising their immune system. Their research identified the gene TLR7 as an essential player in the immune response against SARS-CoV-2. A finding with potentially major consequences for understanding and possibly treatment of COVID-19.

During the wave of COVID-19 patients that flooded Dutch hospitals in the first half of 2020, two young brothers became seriously ill with the SARS-CoV-2 virus and had to be mechanically ventilated in the ICU. One of them died from the consequences of the infection, the other recovered. The severe course of disease in otherwise healthy young brothers was a relatively rare occurrence, especially because the virus mainly affects the elderly. This observation triggered the curiosity of an attentive physician from the MUMC+ department of clinical genetics. She contacted her colleagues in Nijmegen who then investigated why these two young brothers were so severely affected.

Genetic factors

"In such a case, you immediately wonder whether genetic factors could play a role," says geneticist Alexander Hoischen. "Getting sick from an infection is always an interplay between - in this case - the virus and the human immune system. It may be a mere coincidence that two brothers from the same family become so severely ill. But it is also possible that an inborn error of the immune system has played an important role. We investigated this possibility, together with our multidisciplinary team at Radboudumc."

One X-chromosome

All genes (collectively called the exome) of both brothers were sequenced, after which the investigators combed through the data searching for a possible shared cause. Cas van der Made, PhD student and resident at the department of Internal Medicine: "We mainly looked at genes that play a role in the immune system. We know that several of these genes are located on the X-chromosome, and with two brother pairs affected X-chromosomal genes were most suspicious. Women carry two X-chromosomes, while men possess a Y-chromosome apart from the X. Therefore, men have only one copy of the X-chromosomal genes. In case men have a defect in such a gene, there is no second gene that can take over that role, as in women."

Gene identification

That search quickly revealed mutations in the gene encoding for the Toll-like receptor 7, TLR7 for short. There are multiple TLR-genes, which belong to a family of receptors with an important role in the recognition of pathogens (such as bacteria and viruses) and the activation of the immune system. Hoischen: "A few letters were missing in the genetic code of the TLR7 gene. As a result, the code cannot be read properly and hardly any TLR7 protein is produced. TLR7 function has so far never been associated with an inborn error of immunity. But unexpectedly we now have an indication that TLR7 is essential for protection from this coronavirus. So it seems that the virus can replicate undisturbed because the immune system does not get a message that the virus has invaded. Because TLR7, which must identify the intruder and subsequently activate the defense, is hardly present. That could be the reason for the severity of the disease in these brothers."

Additional confirmation

Then, quite unexpectedly, the doctors and researchers at Radboudumc come across another pair of brothers who have fallen seriously ill with COVID-19. Again, they are both under 35 years of age. Both of them were also in the ICU for mechanical ventilation. "Then the question of the role of genetics became even more obvious." says Hoischen. "We also investigated the genetic code of these two brothers, again via the 'rapid-clinical exome' method. This time we saw no deletion, no loss of letters, but a single spelling mistake of one DNA-letter of the TRL7 gene. The effect on the gene is the same, however, because these brothers also do not make sufficient functional TLR7 protein. Suddenly we had four young people with a defect in the same gene, all of whom had fallen seriously ill from the SARS-CoV-2 virus."

Essential role in the defense

Van der Made and colleagues have investigated the consequences of improper functioning of the TLR7 receptor. "Once activated, TLR7 triggers the production of so-called interferons, signaling proteins that are essential in the defense against virus infections," says van der Made. "This immune response is perhaps all the more important in the fight against the SARS-CoV-2 virus, because we know from the literature that the virus has tricks to reduce the production of interferons by immune cells. When we mimic an infection with the coronavirus, we see that immune cells of the patients without properly functioning TLR7 hardly respond, and that minimal amounts of interferons are produced. These tests make it clear that the virus appears to have free rein in people without properly functioning TLR7 because it [the virus] is not recognized by the immune system."

Consequences

"Due to the serious illness of four brothers in two families, so serious that it cost one of the young men his life, we have discovered this condition," says Hoischen. "It seems to be a very specific abnormality, an immunodeficiency, which is mainly related to this coronavirus. None of the four men have previously suffered from immune-related diseases. It is the first time that we can connect a clinical phenomenon so strongly with TLR7."

"This discovery not only provides us with more insight into the fundamental workings of the immune system, but it may also have important consequences for the treatment of severely ill COVID-19 patients," says Frank van de Veerdonk, immunologist and infectiologist. "The substance interferon can be given as a therapy. It is currently being investigated whether administering interferon in COVID-19 can indeed help."

Living under a translucent rock can be quite comfortable -- if you're a moss in the Mojave Desert.

A graduate student at the University of California, Berkeley, found that some mosses in the California desert seek protection from the relentless sun and heat by sheltering under translucent quartz pebbles, essentially using the rocks as sunshades.

The soil under these rocks retains more moisture than exposed desert soil, said Jenna Ekwealor, while enough light leaks through the milky quartz to allow the tiny mosses to remain green with chlorophyll. Mosses actually prefer dim light, making these conditions ideal for growth. In contrast, nearby mosses in full sun are dried up and black.

One species of desert moss seems able to survive at high elevations only under the milky quartz, which occurs in outcroppings scattered around the desert. Mosses don't grow under granitic stones in the area because sunlight can't get through to the soil.

"We were there (in the Mojave) studying the population biology and reproductive biology of mosses, and picking up these cool quartz rocks, like, oh look at this pretty rock," said Ekwealor, an integrative biology doctoral student who works in the University and Jepson Herbaria at UC Berkeley. While all the other mosses were dry and dormant, she "saw that there was moss growing underneath the quartz and it was bright green. That was the first clue that something was different, that they were responding to the environment differently."

Working with her former master's thesis advisor, Kirsten Fisher of California State University, Los Angeles, they placed temperature and humidity sensors under milky quartz pebbles to record the microclimate from September of last year to February of 2020.

"The rock acts as a buffer for the extremes of the climate," Ekwealor said. "The desert is at a high elevation, it gets really hot in the summer and really cold in the winter. And days can be hot, and nights can be cold. The rock keeps the mosses underneath cooler during the hot parts of the year and warmer during the cold periods. The increased relative humidity was just a positive, an important thing for these plants that dry out when the relative humidity is too low."

Astrobiologists have long studied cyanobacteria that live under translucent desert rocks -- a possible model for the types of extreme life that could exist on other planets -- but this is the first green plant known to take advantage of these natural refuges.

"In the desert, for all organisms, it is like life or death all the time," she said. "So anytime you can find a little boost, a little benefit, it makes a really big difference."

Ekwealor and Fisher reported their discovery this week in the journal PLOS ONE.

Cool mosses

As one of the first land plants to evolve more than 300 million years ago, mosses are well adapted to extreme environments, able to survive repeated desiccation and freezing. Some produce sunscreens to protect against intense ultraviolet sunlight. Some can remain essentially dead, with zero metabolic activity, for a decade, and then revive in seconds when wetted. They're found in the Arctic and Antarctic as well as the hottest, driest deserts.

One of the moss species that often lives under milky quartz, Syntrichia caninervis, typically grows on exposed soil in biocrusts, an association with lichens and cyanobacteria. These crusts are a feature of many deserts, protecting the soil from erosion and providing nutrients for other plants.

As part of the desert's biological crust, Syntrichia are inconspicuous -- about 1 millimeter in diameter and 5 millimeters long. They grow only when wet, and since the Mojave may get only five "precipitation events" per year -- half of which could be snow, which is not conducive to growth -- they grow slowly. Ekwealor estimates that Syntrichia grows only a couple of millimeters per year.

The rest of the time, the Syntrichia mosses on exposed soil remain dormant, turning a dark brown-black, possibly as a sunscreen -- something Ekwealor is trying to figure out for her Ph.D. thesis.

She found that, in contrast to the exposed mosses, mosses that crawl under a rock grow about 60% faster.

"The mosses that normally live at that elevation are small and brown on the soil surface, and under the rocks they are tall and green," she said.

At its lowest, the average relative humidity under the rocks was about twice that of exposed soil -- 63% versus 33%. The daily temperature swing in the "hypolithic microenvironment" was reduced by about 4 degrees Celsius (7 degrees Fahrenheit) from that on the soil surface.

A second moss species, Tortula inermis, grows commonly in full sun at lower altitudes, but at the elevation of the study site, 1,900 meters (6,200 feet), it appears to grow only under milky quartz.

"The rocks offer mosses two big benefits: either a boost in their normal habitat, or they get to live in a habitat that you wouldn't normally live in," Ekwealor said.

Though mosses prefer dim, moist conditions, they, like all plants, require some light or they turn white and die. According to her measurements, between 4% and 0.4% of incident light is transmitted through milky quartz rocks, depending on the size of the rock. At her study site, in a place called Sheep Creek Wash, the quartz ranged in thickness from 25 to 14 millimeters, or an inch to two-fifths of an inch.

The researchers suspect that the quartz not only reduces the overall light and heat, but also provides protection from damaging UV rays. Mosses growing under quartz had less pigmented sunscreen than those growing in exposed areas.

A self-described "moss evangelist," Ekwealor is fascinated by the tiny world of mosses, and occasionally leads local moss walks for the bryophyte chapter of the California Native Plant Society.

"For these tiny plants, a thing like this giant quartz rock over you blocking out all the sun and keeping you wet -- it is like a huge habitat," she said. "You can be in the middle of the desert, but a small rock makes you feel like you are in a spring. We have to remember to see the world from the perspective of a very small plant."