Culture

Army scientists have developed the first lethal mouse model of SARS-CoV-2, the virus that causes COVID-19, using mice that were genetically engineered to express the human ACE2 gene--a key mechanism by which the virus enters human cells. In addition to shedding light on the pathogenesis of COVID-19, this work directly contributes to the advancement of medical countermeasures against the virus.

A preview of the paper, authored by Joseph W. Golden, Ph.D. and colleagues at the U.S. Army Medical Research Institute of Infectious Diseases, appears online this week in JCI Insight, a journal published by the American Society for Clinical Investigation.

Developing a small animal model that mirrors the course of human disease is an essential step in advancing vaccines, diagnostics, and treatments to combat this international health crisis. Previous research on SARS-CoV, the virus responsible for the 2003 global outbreak of Severe Acute Respiratory Syndrome, revealed that the virus binds to target cells by means of an interaction between the 139 kDa viral spike protein and the host angiotensin-converting enzyme 2, or ACE2, protein.

The novel coronavirus, SARS-CoV-2, uses the same mechanism to infect cells. In normal mice, however, the virus does not easily bind to ACE2, making it difficult to study the course of infection. So Golden and the USAMRIID team used a special type of mice called K18-hACE2, which are specially bred with the human ACE protein instead of the mouse version. This mouse strain, developed for the original SARS-CoV outbreak by the Stanley Perlman laboratory at the University of Iowa in the early 2000s, was revived and recently produced at the Jackson Laboratory.

USAMRIID's study used two groups of 14 K18-hACE2 mice, infected with two different doses of SARS-CoV-2 administered by the intranasal route, to simulate how humans are exposed to the virus. Each group contained seven male and seven female mice. On day 3, four mice per group were euthanized to assess disease severity, while the remaining ten mice per group were monitored up to 28 days. Overall, the K18-hACE2 mice developed acute disease, including weight loss, lung injury, and brain infection, and ultimately succumbed to the disease, according to the authors.

In addition, the team infected three other types of mice--C57BL/6, BALB/c and RAG2 deficient mice--with a challenge dose of the virus. These animals did not lose weight and none succumbed to the disease.

"Given that the K18-hACE2 animal model is commercially available, it provides an important platform for evaluation of medical countermeasures across multiple laboratories," said Golden.

URBANA, Ill. - Representing some of the most troublesome agricultural weeds, waterhemp, smooth pigweed, and Palmer amaranth impact crop production systems across the U.S. and elsewhere with ripple effects felt by economies worldwide. In a landmark study, scientists have published the most comprehensive genome information to date for all three species, marking a new era of scientific discovery toward potential solutions.

"These genome assemblies will greatly foster further research on these difficult weed species, including better understanding the ways in which they evade damage from herbicides," says Pat Tranel, professor and associate head of the Department of Crop Sciences at the University of Illinois and co-author on the Genome Biology and Evolution study.

Draft genomes had already been published for waterhemp and Palmer amaranth, but techniques used in the Genome Biology and Evolution study provide a much clearer and richer picture of the species' gene sequences, a requisite for many genomic studies.

All three genomes were assembled using advanced long-read sequencing, which maintains the integrity and continuity of the genome similar to the way large puzzle pieces provide a clearer picture of the whole than small pieces. In Palmer amaranth, an additional sequencing technology (chromatin conformation capture sequencing) was used to further order pieces of the genome that were assembled using the long-read information.

"The goal of any genome assembly is to reveal the complete arrangement of genes in the genome, broken into chromosome-sized fragments. Unfortunately, until recently, quality genome assemblies have been very labor intensive and expensive. The previously published draft genomes for these species reported the genome broken into thousands of pieces, while the assemblies we report are down to hundreds. The vast majority of the sequence is now assembled into very large fragments," says Jacob Montgomery, a graduate student working with Tranel and first author on the study.

To further improve the assembly of the genomes for waterhemp and smooth pigweed, the team used an innovative approach known as trio binning, developed in cattle. Not only had this technique never before been fully utilized in plants, it had also not been used with parents from different species.

In normal reproduction, male and female parents each contribute one copy of every gene to their offspring. In this case, offspring are diploid, meaning they have two copies of every gene. In the study, the team created hybrid offspring from two separate species: waterhemp and smooth pigweed. These offspring are still diploid, but the trio binning technique allowed the researchers to pull apart and isolate the two copies from each parent species, resulting in haploid (single copy) genomes for each.

"This approach resolved a problem in the previous waterhemp genome assembly. When parent alleles (copies of each gene) are very different from each other, as is often the case in outcrossing species such as waterhemp, the genome assembly program interprets them to be different genes," Tranel says. "With only one allele from each species, we were able to obtain a much cleaner assembly of their gene sequences."

Detlef Weigel, director of the Max Planck Institute for Developmental Biology and co-author on the study, adds, "I am a big fan of the new advanced sequencing techniques, but even though they should theoretically be sufficient to sort out the arrangement of genes, in practice they are not. This is where genetics can help out, using information on whether genes were inherited from mom or dad. This allowed us to assign each gene to either a maternal or paternal chromosome."

The researchers specifically chose waterhemp as the male parent in the smooth pigweed × waterhemp cross because the previously published waterhemp genome was from a female plant. Tranel is pursuing research to understand the genetic basis for maleness and femaleness in waterhemp and Palmer amaranth, with potential applications toward introducing female sterility as a future control method.

"The genomes of the male waterhemp and Palmer amaranth already have enabled my group to make rapid progress on identifying the potential genes that could be responsible for the determination of sex (male or female) in both species," Tranel says.

Importantly, the genomes for all three species could start to chip away at the problem of herbicide resistance in these weeds. More and more, scientists are uncovering evidence of non-target-site or metabolic resistance in waterhemp and Palmer amaranth, allowing the weeds to detoxify herbicides before they can cause damage. Unfortunately, it is usually very difficult to determine which specific enzyme, among hundreds, is responsible for detoxifying the herbicide.

Now, researchers will essentially be able to sort through a list to find the culprit with the hope of either knocking out the enzyme responsible or modifying the herbicide molecule to evade detoxification.

"Innovation is essential for the future of agriculture. We at BASF are working continuously on improving our products and services including sustainable solutions for the management of herbicide-resistant weeds. We want to better understand the amaranth biochemical resistance mechanisms in order to offer farmers new products and solutions for optimal control of key weeds," says Jens Lerchl, head of early biology research on herbicides at BASF and study co-author. Lerchl coordinated the Palmer amaranth genome work with KeyGene/Wageningen -The Netherlands.

"The area of genome sequencing is highly dynamic. That is why BASF chose KeyGene as the partner for both latest sequencing technology and bioinformatics. Together with the expertise of the University of Illinois and Max Planck Society, we were able to compare genomes and address specific biological topics," Lerchl says. In addition to collaborating on this research, BASF is also a founding member of the International Weed Genomics Consortium, led by Colorado State University aiming at the sequencing and analysis of ten high priority key weeds.

Scoliosis is the most common spinal deformity affecting pediatric patients. A posterior spinal fusion (PSF) is the gold standard treatment for patients with curves exceeding 45 degrees, but the procedure's drawbacks include the loss of spinal mobility, persistent pain and adjacent segment disc disease. However, a new retrospective study from the University of Missouri School of Medicine and MU Health Care shows an alternative to PSF called vertebral body tethering (VBT) yields promising results with fewer long-term consequences for a specific group of scoliosis patients.

VBT is an alternative to PSF for scoliosis patients who still have growth remaining and flexibility of their spine. Screws are attached in a minimally invasive fashion to the thoracic or lumbar vertebra in the curved area of the spine. A polyethylene cord connects the screws and tension straightens the spine, correcting the scoliosis. MU Health Care is one of only a handful of medical centers in the U.S. offering the procedure. Pediatric orthopaedic surgeon Dan Hoernschemeyer, MD, is the principal investigator for the study and has performed more than 85 VBT surgeries on patients from around the country.

"If the child's spine has more than 45 degrees of scoliosis and still has some growth remaining, VBT is a way to correct the scoliosis, preserve motion and modulate normal growth instead of fusing it," Hoernschemeyer said. "Our study examined the radiographic and clinical outcomes of idiopathic scoliosis patients with various curve patterns treated with VBT."

Hoernschemeyer and his team conducted a retrospective review of 29 consecutive patients with 2-5 year follow-ups. Successful outcomes were defined by a curve of less than 30 degrees in patients who reached skeletally maturity and had not receive a PSF. At the latest follow-up, 27 patients reached skeletal maturity and 74% achieved clinical success.

"Despite our patient population being slightly more mature at the time of surgery than when compared to previous studies, we found a higher success rate and a lower revision rate," Hoernschemeyer said. "Our overall revision rate was 21% and a PSF was avoided in 93% of patients, indicating that VBT may be a reliable treatment option for adolescent scoliosis."

The most common complication that led to revision involved tether breakage. Fourteen patients experienced a broken tether, and half required either a revision surgery or PSF.

"While the exact role of VBT in the management of adolescent scoliosis continues to be defined, the data from this study supports the fact that this surgical procedure should be considered as a treatment option for children with scoliosis and an alternative to fusion," Hoernschemeyer said.

AMHERST, Mass. - In results released this week, an international team of wildlife ecologists reports that the trend toward more reliance on private game farms and reserves to manage and conserve free-ranging carnivores in South Africa is more complicated than it appears - "a mosaic" of unequal protection across different land management types.

Chris Sutherland at the University of Massachusetts Amherst, with first author and doctoral student Gonçalo Curveira-Santos of the Centre for Ecology, Evolution and Environmental Changes at the University of Lisbon, used a large network of camera traps to study occupancy of free-ranging carnivore species including leopards, hyenas, jackals and mongooses in different habitats and levels of protection in northeast South Africa.

Curveira-Santos says, "Widespread conversion of agricultural and livestock areas for commercial wildlife industry, ecotourism and hunting is a major component of conservation in South Africa. Management initiatives and conservation outcomes are typically focused on the large charismatic species like lions or cheetahs, but we know very little about how unmanaged, free-ranging carnivores respond to landscapes defined by varying management and conservation models."

He adds, "Our results support the notion that the private reserves or game ranches play a complementary role to formal protected areas, but that it's also important to recognize they do not play the same role, and may not be a conservation panacea. For governments, it's attractive to move conservation to the private sector, but for us to assess the conservation benefits of doing so, we need some benchmarks, and protected areas under long-term formal protection are important references to a "natural state."

Writing in the Journal of Applied Ecology, the researchers explain how they conducted a survey to explore the relative conservation role of the private and formal protected areas for South African free-ranging carnivores.

With reserve rangers and staff, Curveira-Santos established a camera trap network to survey a natural quasi-experimental setting in northern KwaZulu-Natal, South Africa. The area offers a "protection gradient" from a provincial protected area, the 108-year-old uMkhuze Game Reserve, part of iSimangaliso Wetland Park UNESCO World Heritage Site, to a private ecotourism reserve, Mun-ya-wana Private Game Reserve, to commercial game ranches and traditional communal areas with villages as a disturbance reference.

Sutherland points out that this was "a phenomenal field effort" that used 294 trail cameras for an average 75 days each. The motion-activated cameras generated 7,224 images of 13 free-ranging carnivores from small mongooses to much larger leopards and spotted hyenas. The researchers analyzed multi-species site occupancy data, stratifying by four protection levels, and formally compared community patterns at several scales.

Overall, they found species number and identity was similar in the protected area, private reserve and game ranches and markedly lower in the communal area. However, they observed "important variation in species occupancy rates - as a proxy for abundance - that was mainly driven by the level and nature of protection."

They say findings provide "support for the added value of multi-tenure conservation estates augmenting and connecting South Africa's protected areas." Further, similar carnivore richness between the private reserve and game ranches and higher occupancy compared to communal lands shows that carnivores can thrive in private wildlife areas.

However, for most species, occupancy rates were highest in the formal protected area, Sutherland notes, "but clearly more research is needed to understand what factors may be hindering species recovery to the levels observed in the formal protected area, and importantly, what the ecological consequences of such patterns are."

Curveira-Santos adds, "Our point is that the formal old protected areas may play a key role that cannot be replicated easily," especially often-overlooked free-ranging carnivores outside protected areas that seem to respond differently to different management approaches. "In general terms," he adds, "our work adds to the call for a more holistic perspective of wildlife for effective conservation planning. In the meantime, ensuring the long-term maintenance of formal protected areas is probably our safest bet."

Among the many winter survival strategies in the animal world, hibernation is one of the most common. With limited food and energy sources during winters - especially in areas close to or within polar regions - many animals hibernate to survive the cold, dark winters. Though much is known behaviorally on animal hibernation, it is difficult to study in fossils.

According to new research, this type of adaptation has a long history. In a paper published Aug. 27 in the journal Communications Biology, scientists at Harvard University and the University of Washington report evidence of a hibernation-like state in an animal that lived in Antarctica during the Early Triassic, some 250 million years ago.

The creature, a member of the genus Lystrosaurus, was a distant relative of mammals. Lystrosaurus were common during the Permian and Triassic periods and are characterized by their turtle-like beaks and ever-growing tusks. During Lystrosaurus' time, Antarctica lay largely within the Antarctic Circle and experienced extended periods without sunlight each winter.

"Animals that live at or near the poles have always had to cope with the more extreme environments present there," said lead author Megan Whitney, a postdoctoral researcher at Harvard University in the Department of Organismic and Evolutionary Biology, who conducted this study as a UW doctoral student in biology. "These preliminary findings indicate that entering into a hibernation-like state is not a relatively new type of adaptation. It is an ancient one."

The Lystrosaurus fossils are the oldest evidence of a hibernation-like state in a vertebrate animal and indicate that torpor -- a general term for hibernation and similar states in which animals temporarily lower their metabolic rate to get through a tough season -- arose in vertebrates even before mammals and dinosaurs evolved.

Lystrosaurus arose before Earth's largest mass extinction at the end of the Permian Period - which wiped out 70% of vertebrate species on land - and somehow survived. It went on to live another 5 million years into the Triassic Period and spread across swathes of Earth's then-single continent, Pangea, which included what is now Antarctica. "The fact that Lystrosaurus survived the end-Permian mass extinction and had such a wide range in the early Triassic has made them a very well-studied group of animals for understanding survival and adaptation," said co-author Christian Sidor, a UW professor of biology and curator of vertebrate paleontology at the Burke Museum.

Today, paleontologists find Lystrosaurus fossils in India, China, Russia, parts of Africa and Antarctica. The creatures grew to be 6 to 8 feet long, had no teeth, but bore a pair of tusks in the upper jaw. The tusks made Whitney and Sidor's study possible because, like elephants, Lystrosaurus tusks grew continuously throughout their lives. Taking cross-sections of the fossilized tusks revealed information about Lystrosaurus metabolism, growth and stress or strain. Whitney and Sidor compared cross-sections of tusks from six Antarctic Lystrosaurus to cross-sections of four Lystrosaurus from South Africa. During the Triassic, the collection sites in Antarctica were roughly 72 degrees south latitude -- well within the Antarctic Circle. The collection sites in South Africa were more than 550 miles north, far outside the Antarctic Circle.

The tusks from the two regions showed similar growth patterns, with layers of dentine deposited in concentric circles like tree rings. The Antarctic fossils, however, held an additional feature that was rare or absent in tusks farther north: closely-spaced, thick rings, which likely indicate periods of less deposition due to prolonged stress, according to the researchers. "The closest analog we can find to the 'stress marks' that we observed in Antarctic Lystrosaurus tusks are stress marks in teeth associated with hibernation in certain modern animals," said Whitney.

The researchers cannot definitively conclude that Lystrosaurus underwent true hibernation. The stress could have been caused by another hibernation-like form of torpor, such as a more short-term reduction in metabolism. Lystrosaurus in Antarctica likely needed some form of hibernation-like adaptation to cope with life near the South Pole, said Whitney. Though Earth was much warmer during the Triassic than today -- and parts of Antarctica may have been forested -- plants and animals below the Antarctic Circle would still experience extreme annual variations in the amount of daylight, with the sun absent for long periods in winter.

Many other ancient vertebrates at high latitudes may also have used torpor, including hibernation, to cope with the strains of winter, Whitney said. But many famous extinct animals, including the dinosaurs that evolved and spread after Lystrosaurus died out, don't have teeth that grow continuously.

"To see the specific signs of stress and strain brought on by hibernation, you need to look at something that can fossilize and was growing continuously during the animal's life," said Sidor. "Many animals don't have that, but luckily Lystrosaurus did."
If analysis of additional Antarctic and South African Lystrosaurus fossils confirms this discovery, it may also settle another debate about these ancient, hearty animals.
"Cold-blooded animals often shut down their metabolism entirely during a tough season, but many endothermic or 'warm-blooded' animals that hibernate frequently reactivate their metabolism during the hibernation period," said Whitney. "What we observed in the Antarctic Lystrosaurus tusks fits a pattern of small metabolic 'reactivation events' during a period of stress, which is most similar to what we see in warm-blooded hibernators today." If so, this distant cousin of mammals is a reminder that many features of life today may have been around for hundreds of millions of years before humans evolved to observe them.

Organs in animals and in humans have one thing in common: they are bounded by so-called epithelial cells. These, along with the muscle, connective and nervous tissues, belong to the basic types of tissue. Epithelial cells form special connections with one another in order to prevent substances or pathogens from passing between the cells, i.e. they have a protective and sealing function for the body. Researchers at the Institute of Animal Physiology at the University of Munster have now found out how two proteins called Anakonda and M6 interact in epithelial cells in fruit flies in order to produce a functioning barrier at so-called tricellular contacts.

These corner points between three cells - so-called tricellular junctions (TCJs) - are a preferred route for migrating cells as well as for bacterial pathogens entering into the body. Although the formation of the barrier function between two epithelial cells has already been well examined, much less is known about the biology of the tricellular contacts. The working group headed by Prof. Dr. Stefan Luschnig is aiming to gain a better understanding of the structure and dynamics of epithelial barriers, hoping that this can contribute in the long term to developing more effective forms of diagnosis and treatment for example of bacterial infections or inflammation reactions. The study has been published in the journal "Current Biology".

Background and method

TCJs play an essential role in the functioning of the barrier between epithelial cells and in the migration of cells across tissue boundaries. Special protein complexes at the tricellular contacts are responsible for the sealing properties of these structures. Despite the fundamental roles of tricellular contacts in epithelial biology, their molecular structure and the dynamics of their assembly and remodelling have so far been insufficiently understood.

In order to study this process, the researchers visualized the M6 protein in embryos of the fruit fly Drosophila with a fluorescent marker and, using a high-resolution confocal microscope, they observed the processes taking place in the tricellular contacts in the living cells. As a result of their studies, Stefan Luschnig and his team discovered that the M6 protein is responsible for keeping the Anakonda protein stable in its place at the cell membrane of the TCJs.

When the researchers removed the M6 protein, the Anakonda protein - though it still reached its destination at the cell membrane - was not anchored stably there. The consequence is a permeable tricellular junction. These and other findings led the researchers to conclude that the two proteins depend on each other and form a complex, which is of crucial importance for the stabilising properties of cell contacts and consequently for survival of the animal. "On the basis of these results obtained from the model organism Drosophila", says Stefan Luschnig, "we can gain fundamental insights into the structure and development of epithelial tissues in more complex animals, as well as in humans."

The Earth is the only planet known to have liquid water on its surface, a fundamental characteristic when it comes to explaining the emergence of life. However, was this water always present in the rocks that made up our planet? Alternatively, was it delivered later by asteroids and comets that bombarded the Earth? Or did the Earth's water originate from a combination of both sources? In the journal Science dated 28 August 2020, scientists from the Centre de Recherches Pétrographiques et Géochimiques in Nancy (CNRS/Université de Lorraine) contribute to this debate by showing that most of the water present on the Earth today has probably been there right from the very beginning. And yet the Earth was formed in a region of the Solar System where temperatures were too high for water to condense and clump together with other solids as ice, long supporting the hypothesis of a late addition of water. However, the amount of water present in the rocks that made up the Earth had never been accurately estimated. The scientists focused on meteorites with a composition similar to that of the Earth, called enstatite chondrites (1), and more specifically on a small number of these that underwent little heating over the course of their lifetime and thus still exhibit a primitive composition. Using two complementary techniques, they measured their content in hydrogen and determined precisely where part of this was located. Their results show that the Earth's primitive rocks probably contained enough water to provide at least three times the amount of water in the Earth's oceans, and possibly much more. In addition, the hydrogen in these meteorites has the same isotopic composition (2) as that of the water stored in the Earth's mantle, while the isotopic composition of the oceans is consistent with a mixture containing 95% of water from the enstatite chondrites and a mere 5% of water delivered by comets or water-rich asteroids. The Earth therefore appears to have obtained the overwhelming majority of its water from its constituent materials.

Over the past few months, a number of drugs have been under investigation to treat COVID-19 without well-established safety or data to support these claims. However, some of these unproven therapies may have underlying genetic reasons for not being effective and resulting in fatal adverse effects as found with hydroxychloroquine.

University of Minnesota College of Pharmacy faculty Pamala Jacobson and Melanie Nicol, and Pediatric Hematology/Oncology Fellow Takuto Takahashi recently published a peer-reviewed study in Nature Genomic Medicine about how individualization with pharmacogenomics — the study of how genes affect a person's response to drugs — may improve the efficiency and safety of these drugs.

“The application of pharmacogenomic tests can help eliminate fatal hypersensitivity for patients prescribed certain drugs,” said Jacobson. “We asked the question if selecting a COVID-19 medication or the dose using an individual's genetic information could improve effectiveness or safety.”

“One of the biggest success stories of using pharmacogenomics is with the HIV treatment abacavir,” said Nicol. “Which is now a standard test for potential treatment for those living with HIV and has virtually eliminated fatal hypersensitivity associated with that drug.”

The study looked at a variety of literature for drug therapies for COVID-19 — including hydroxychloroquine, remedesivier, tocilizumab and steroids — on PubMed. The researchers found that:

there are several gene variants that alter how an individual’s body metabolizes and processes COVID-19 therapies and may increase the risk of adverse effects;
that the risk of taking these therapies is complex since patients with COVID-19 are usually taking multiple other medications and have underlying conditions that affect the drug;
and the data for the pharmacogenomics on COVID-19 is limited due to the early stages of the clinical trials investigating treatments.

“While we did not find direct evidence to support use of pharmacogenomic testing for COVID-19, we did identify many actionable genetic markers that may have promise to improve efficacy and safety,” said Jacobson. “Clinical studies in patients with COVID-19 are needed before routine testing can be recommended.”

August 27, 2020 - COVID-19 has upended essentially every sector of the economy, and none more so than healthcare. Healthcare leaders from across the United States share their experiences with disruption and innovation in responding to the COVID-19 crisis in the Fall 2020 issue of Frontiers of Health Services Management, a publication of the American College of Healthcare Executives (ACHE). This journal is published in the Lippincott portfolio by Wolters Kluwer.

Leaders at Montefiore Health System in the Bronx, New York, describe a process of "creative destruction" leading to accelerated innovation - especially in terms of rapidly ramping up digital health capabilities. "In this new reality, digital innovation is fundamental for healthcare organizations as they make their transition into recovery," according to the article by Montefiore vice president and chief of staff Jeffrey B. Short and associate vice president and patient access transformation officer Adrin Mammen, FACHE. The theme for the new issue of Frontiers is "Response and Recovery: Healthcare Navigates the COVID-19 Pandemic."

COVID-19 'Can Serve as the Catalyst for Digital Innovation' in Healthcare

As New York saw its first cases of COVID-19, Montefiore leadership realized they would soon face an exponential growth rate, leading to shortages of hospital and ICU beds. Citing the classic theory of market disruption and resulting innovations, Mr. Short and Ms. Mammen write, "In this state of uncertainty, the invisible hands of the changing market economy drove Montefiore to pursue creative destruction and accelerate innovation."

"Driven by the virus, we quickly put new ideas into practice," the authors write. Leadership established an incident command structure, providing agility to make decisions and react to challenges. Resources were placed under central command; spaces throughout the Montefiore system were swiftly converted for inpatient use, doubling physical capacity.

Faced with disruption of normal care, leaders rapidly implemented a digital innovation program. An artificial intelligence (AI)-based, coronavirus-specific chatbot was introduced, leading to more than 18,000 engagements within 30 days. Within weeks, the chatbot was extended to inquiries other than COVID-19. "Amid this new sense of urgency, innovations that would typically have taken many years to operationalize at Montefiore have been completed in a matter of days," Mr. Short and Ms. Mammen write.

Responding to plummeting in-person visits, leaders designed and implemented a new telehealth solution. This became especially valuable as it was apparent that patients remained hesitant to make appointments, even after in-person visits resumed. Before the pandemic, Montefiore had no telehealth program; by April, more than 80 percent of visits had shifted to telehealth.

These lessons in accelerated innovation have important implications for the "new normal" in a post-pandemic world. Montefiore leaders have established a new tele-ICU command center, inpatient consultations via telehealth, real-time performance management, and extension of AI as an essential decision-making tool. "As the barriers of the past come down, Montefiore is embracing creative destruction," Mr. Short and Ms. Mammen conclude. "As a result, the excitement of digital innovation permeates the entire organization."

The COVID-19 pandemic "continues to demonstrate healthcare's vulnerabilities and is a force with such strength that it affects all aspects of care," according to an introduction by Frontiers editor Trudy Land, FACHE. She adds: "It is imperative for organizations to move forward from a precarious state and develop stronger systems for their communities."

The COVID-19-themed issue presents reports from leaders at nine healthcare organizations across the United States - from large healthcare systems like Montefiore serving a population of millions in New York City, to a regional healthcare corporation serving three Native American tribes across 6,000 square miles in Arizona. Ms. Land writes, "[The authors] share how they are responding to the coronavirus and navigating toward recovery, implementing changes and discovering innovations along the way."

Changes to water masses which are stored on the continents can be detected with the help of satellites. The data sets on the Earth's gravitational field which are required for this, stem from the GRACE and GRACE-FO satellite missions. As these data sets only include the typical large-scale mass anomalies, no conclusions about small scale structures, such as the actual distribution of water masses in rivers and river branches, are possible. Using the South American continent as an example, the Earth system modellers at the German Research Centre for Geosciences GFZ, have developed a new Deep-Learning-Method, which quantifies small as well as large-scale changes to the water storage with the help of satellite data. This new method cleverly combines Deep-Learning, hydrological models and Earth observations from gravimetry and altimetry.

So far it is not precisely known, how much water a continent really stores. The continental water masses are also constantly changing, thus affecting the Earth's rotation and acting as a link in the water cycle between atmosphere and ocean. Amazon tributaries in Peru, for example, carry huge amounts of water in some years, but only a fraction of it in others. In addition to the water masses of rivers and other bodies of fresh water, considerable amounts of water are also found in soil, snow and underground reservoirs, which are difficult to quantify directly.

Now the research team around primary author Christopher Irrgang developed a new method in order to draw conclusions on the stored water quantities of the South American continent from the coarsely-resolved satellite data. "For the so called down-scaling, we are using a convolutional neural network, in short CNN, in connection with a newly developed training method", Irrgang says. "CNNs are particularly well suited for processing spatial Earth observations, because they can reliably extract recurrent patterns such as lines, edges or more complex shapes and characteristics."

In order to learn the connection between continental water storage and the respective satellite observations, the CNN was trained with simulation data of a numerical hydrological model over the period from 2003 until 2018. Additionally, data from the satellite altimetry in the Amazon region was used for validation. What is extraordinary, is that this CNN continuously self-corrects and self-validates in order to make the most accurate statements possible about the distribution of the water storage. "This CNN therefore combines the advantages of numerical modelling with high-precision Earth observation" according to Irrgang.

The researchers' study shows that the new Deep-Learning-Method is particularly reliable for the tropical regions north of the -20° latitude on the South American continent, where rain forests, vast surface waters and also large groundwater basins are located. Same as for the groundwater-rich, western part of South America's southern tip. The down-scaling works less well in dry and desert regions. This can be explained by the comparably low variability of the already low water storage there, which therefore only have a marginal effect on the training of the neural network. However, for the Amazon region, the researchers were able to show that the forecast of the validated CNN was more accurate than the numerical model used.

In future, large-scale as well as regional analysis and forecasts of the global continental water storage will be urgently needed. Further development of numerical models and the combination with innovative Deep-Learning-Methods will take up a more important role in this, in order to gain comprehensive insight into continental hydrology. Aside from purely geophysical investigations, there are many other possible applications, such as studying the impact of climate change on continental hydrology, the identification of stress factors for ecosystems such as droughts or floods, and the development of water management strategies for agricultural and urban regions.

In a year defined by obstacles, a University of Illinois at Urbana-Champaign student rocket team persevered. Working together across five time zones, they successfully designed a hybrid rocket engine that uses paraffin and a novel nitrous oxide-oxygen mixture called Nytrox. The team has its sights set on launching a rocket with the new engine at the 2021 Intercollegiate Rocketry and Engineering Competition.

"Hybrid propulsion powers Virgin Galactic's suborbital tourist spacecraft and the development of that engine has been challenging. Our students are now experiencing those challenges first hand and learning how to overcome them," said faculty adviser to the team Michael Lembeck.

Last year the team witnessed a number of catastrophic failures with hybrid engines utilizing nitrous oxide. The propellant frequently overheated in the New Mexico desert, where the IREC competition is held. Lembeck said this motivated the team to find an alternative fuel that could remain stable at temperature. Nytrox surfaced as the solution to the problem.

As the team began working on the engine this past spring semester, excitement to conduct hydrostatic testing of the ground oxidizer tank vessel quickly turned to frustration as the team lacked a safe test location.

Team leader Vignesh Sella said, "We planned to conduct the test at the U of I's Willard airport retired jet engine testing facility. But the Department of Aerospace Engineering halted all testing until safety requirements could be met."

Sella said they were disheartened at first, but rallied by creating a safety review meeting along with another student rocket group to examine their options.

"As a result of that meeting, we came up with a plan to move the project forward. The hybrid team rigorously evaluated our safety procedures, and had our work reviewed by Dr. Dassou Nagassou, the Aerodynamics Research Lab manager. He became a great resource for us, and a very helpful mentor."

Sella and Andrew Larkey also approached Purdue University to draw from their extensive experience in the realm of rocket propulsion. They connected with Chris Nielson who is a graduate student and lab manager at Purdue. They did preliminary over-the-phone design reviews and were eventually invited to conduct their hydrostatic and cold-flow testing at Purdue's Zucrow Laboratories, a facility dedicated to testing rocket propulsion with several experts in the field on-site.

"We sent a few of the members there to scout the location and take notes before bringing the whole team there for a test," Sella said. "These meetings, relationships, and advances, although they may sound smooth and easy to establish, were arduous and difficult to attain. It was a great relief to us to have the support from the department, a pressure vessel expert as our mentor, and Zucrow Laboratories available to our team."

The extended abstract, which the team had submitted much earlier to the AIAA Propulsion and Energy conference, assumed the engine would have been assembled and tested before the documentation process began. Team leader Vignesh Sella said they wanted to document hard test data but had to switch tactics in March. The campus move to online-only classes also curtailed all in-person activities, including those of registered student organizations like ISS.

"As the disruptions caused by COVID-19 required us to work remotely, we pivoted the paper by focusing on documenting the design processes and decisions we made for the engine. This allowed us to work remotely and complete a paper that wasn't too far from the original abstract. Our members, some of whom are international, met on Zoom and Discord to work on the paper together virtually, over five time zones," Sella said.

Sella said he and the entire team are proud of what they have accomplished and are "returning this fall with a vengeance."

The Illinois Space Society is a technical, professional, and educational outreach student organization at the U of I in the Department of Aerospace Engineering. The society consists of 150 active members. The hybrid rocket engine team consisted of 20 members and is one of the five technical projects within ISS. The project began in 2013 with the goal of constructing a subscale hybrid rocket engine before transitioning to a full-scale engine. The subscale hybrid rocket engine was successfully constructed and hot fired in the summer of 2018, yielding the positive test results necessary to move onto designing and manufacturing a full-scale engine.

"After the engine completes its testing, the next task will be integrating the engine into the rocket vehicle," said Sella "This will require fitting key flight hardware components within the geometric constraints of a rocket body tube and structurally securing the engine to the vehicle."

In June 2021, the rocket will be transported to Spaceport America in Truth or Consequences for its first launch.

While high greenhouse gas emissions and biodiversity loss are often associated with rapid land-use change in Indonesia, impacts on local water cycles have been largely overlooked. Researchers from the University of Göttingen, IPB University in Bogor and BMKG in Jakarta have now published a new study on this issue. They show that the expansion of monocultures, such as oil palm and rubber plantations, leads to more frequent and more severe flooding. The multidisciplinary team explains this increase in flooding with a complex interplay of ecohydrological and social processes, including soil degradation in monocultures, the expansion of oil palm plantations into wetlands, and the construction of flood protection dams. The results have been published in the journal Ecology & Society.

For the study, the authors conducted almost 100 interviews with Indonesian smallholders, people from the village and decision-makers in the Jambi province of Sumatra. They then compared and supplemented their analyses of these results with scientific measurements of precipitation, river and groundwater levels, soil properties as well as land use mapping from the region. "Many studies on the relationship between land use changes and flooding are only based on analyses by individual disciplines and thus provide only fragmentary insights into the underlying processes," says lead author Jennifer Merten, Department of Human Geography at the University of Göttingen. "It was therefore important for us to use the widest possible range of data from different disciplines and also to include observations from the local population."

In their study, the scientists of the German-Indonesian Collaborative Research Centre EFForTS (Ecological and Socio-Economic Functions of Tropical Lowland Rainforest Transformation Systems) show that the current expansion of oil palm and rubber plantations has a significant impact on local water cycles. "The large-scale land-use change leads to a compaction of the soil, so that less rain is absorbed by the soil and the water quickly runs off at the surface," explains co-author Christian Stiegler, Bioclimatology Group at the University of Göttingen. "In particular, the advancing destruction of floodplains plays an important role in this process." From the perspective of the village population, the construction of flood dams and drainage channels also contributes to a change in local patterns of flooding. As oil palm plantations in particular are increasingly cultivated in wetlands such as river floodplains or peatlands, larger plantation owners are trying to control flooding on their land by means of such constructions. "However, such dams often lead to increased flooding on neighbouring smallholder plantations," Merten reports following her experiences from the area. This means that the observed increase in flooding also leads to new social tensions and conflicts.

In order to reduce the impact of land use change on the water cycle, soil protection and improved land use planning, especially in floodplains and wetlands, can play an important role. "Yet, it is just as important to regulate and control landscape interventions for flood protection and drainage more closely," says Merten. "Otherwise it might happen that the effects of increasing flooding will affect above all the poorest in society, because larger companies simply pass on the water."

In a landmark study, scientists using NASA's Hubble Space Telescope have mapped the immense envelope of gas, called a halo, surrounding the Andromeda galaxy, our nearest large galactic neighbor. Scientists were surprised to find that this tenuous, nearly invisible halo of diffuse plasma extends 1.3 million light-years from the galaxy--about halfway to our Milky Way--and as far as 2 million light-years in some directions. This means that Andromeda's halo is already bumping into the halo of our own galaxy.

They also found that the halo has a layered structure, with two main nested and distinct shells of gas. This is the most comprehensive study of a halo surrounding a galaxy.

"Understanding the huge halos of gas surrounding galaxies is immensely important," explained co-investigator Samantha Berek of Yale University in New Haven, Connecticut. "This reservoir of gas contains fuel for future star formation within the galaxy, as well as outflows from events such as supernovae. It's full of clues regarding the past and future evolution of the galaxy, and we're finally able to study it in great detail in our closest galactic neighbor."

"We find the inner shell that extends to about a half million light-years is far more complex and dynamic," explained study leader Nicolas Lehner of the University of Notre Dame in Indiana. "The outer shell is smoother and hotter. This difference is a likely result from the impact of supernova activity in the galaxy's disk more directly affecting the inner halo."

A signature of this activity is the team's discovery of a large amount of heavy elements in the gaseous halo of Andromeda. Heavier elements are cooked up in the interiors of stars and then ejected into space--sometimes violently as a star dies. The halo is then contaminated with this material from stellar explosions.

The Andromeda galaxy, also known as M31, is a majestic spiral of perhaps as many as 1 trillion stars and comparable in size to our Milky Way. At a distance of 2.5 million light-years, it is so close to us that the galaxy appears as a cigar-shaped smudge of light high in the autumn sky. If its gaseous halo could be viewed with the naked eye, it would be about three times the width of the Big Dipper. This would easily be the biggest feature on the nighttime sky.

Through a program called Project AMIGA (Absorption Map of Ionized Gas in Andromeda), the study examined the light from 43 quasars--the very distant, brilliant cores of active galaxies powered by black holes--located far beyond Andromeda. The quasars are scattered behind the halo, allowing scientists to probe multiple regions. Looking through the halo at the quasars' light, the team observed how this light is absorbed by the Andromeda halo and how that absorption changes in different regions. The immense Andromeda halo is made of very rarified and ionized gas that doesn't emit radiation that is easily detectable. Therefore, tracing the absorption of light coming from a background source is a better way to probe this material.

The researchers used the unique capability of Hubble's Cosmic Origins Spectrograph (COS) to study the ultraviolet light from the quasars. Ultraviolet light is absorbed by Earth's atmosphere, which makes it impossible to observe with ground-based telescopes. The team used COS to detect ionized gas from carbon, silicon, and oxygen. An atom becomes ionized when radiation strips one or more electrons from it.

Andromeda's halo has been probed before by Lehner's team. In 2015, they discovered that the Andromeda halo is large and massive. But there was little hint of its complexity; now, it's mapped out in more detail, leading to its size and mass being far more accurately determined.

"Previously, there was very little information--only six quasars--within 1 million light-years of the galaxy. This new program provides much more information on this inner region of Andromeda's halo," explained co-investigator J. Christopher Howk, also of Notre Dame. "Probing gas within this radius is important, as it represents something of a gravitational sphere of influence for Andromeda."

Because we live inside the Milky Way, scientists cannot easily interpret the signature of our own galaxy's halo. However, they believe the halos of Andromeda and the Milky Way must be very similar since these two galaxies are quite similar. The two galaxies are on a collision course, and will merge to form a giant elliptical galaxy beginning about 4 billion years from now.

Scientists have studied gaseous halos of more distant galaxies, but those galaxies are much smaller on the sky, meaning the number of bright enough background quasars to probe their halo is usually only one per galaxy. Spatial information is therefore essentially lost. With its close proximity to Earth, the gaseous halo of Andromeda looms large on the sky, allowing for a far more extensive sampling.

"This is truly a unique experiment because only with Andromeda do we have information on its halo along not only one or two sightlines, but over 40," explained Lehner. "This is groundbreaking for capturing the complexity of a galaxy halo beyond our own Milky Way."

In fact, Andromeda is the only galaxy in the universe for which this experiment can be done now, and only with Hubble. Only with an ultraviolet-sensitive future space telescope will scientists be able to routinely undertake this type of experiment beyond the approximately 30 galaxies comprising the Local Group.

"So Project AMIGA has also given us a glimpse of the future," said Lehner.

August 27, 2020 (Seattle, Wash.)--Discoveries from the Benaroya Research Institute at Virginia Mason (BRI) have identified a new cellular protection pathway that targets a common vulnerability in several different pandemic viruses, and collaborators at Case Western Reserve University, Boston University School of Medicine and MRIGlobal have shown that this pathway can protect cells from infection by Ebola virus and coronaviruses, like SARS-CoV-2. Published today in Science, these new findings provide a better understanding of cellular mechanisms involved in viral resistance that can inform future treatments and therapies for viral infectious diseases.

The research illuminates a completely new role for the two genes identified and a unique approach to inhibiting virus fusion and entry into human cells--getting us one step closer to the next generation of antiviral therapies. Researchers used a transposon-mediated gene-activation screen to search for new genes that can prevent infection by Ebola virus. This new screening strategy--that serves as a blueprint for uncovering resistance mechanism against other dangerous pathogens-- found that the gene MHC class II transactivator (CIITA) induces resistance in human cell lines by activating the expression of a second gene, CD74. One form of CD74, known as p41, disrupts the processing of proteins on the coat of the Ebola virus protein by cellular proteases called Cathepsins. This prevents entry of the virus into the cell and infection. CD74 p41 also blocked the Cathepsin-dependent entry pathway of coronaviruses, including SARS-CoV-2.

"Uncovering these new cellular protection pathways is incredibly important for understanding how we disrupt or change the virus infection cycle to illicit better protection against viruses like Ebola or SARS-CoV-2." said Adam Lacy-Hulbert, Ph.D., Principal Investigator, BRI and lead author on the study. "And our new strategy helps us find mechanisms that have eluded conventional genetic screens."

The findings illustrate a new role for genes previously thought to be involved in more conventional T cell and B cell mediated immune responses. For example, CIITA was understood as important for communication between immune cells, but it had not previously been seen as a way for cells to defend themselves against viruses.

"As a virologist, I am excited not just about what this means for Ebola virus, but about the broader implications for other viruses," said Anna Bruchez, Ph.D., Instructor in Pathology, Case Western Reserve University and co-author on the study. "Many viruses, including coronaviruses, use cathepsin proteases to help them infect cells. Fortunately, when SARS-CoV-2 emerged, I had recently moved to Case Western, and was able to use their specialized BSL3 laboratories to show the CD74 pathway also blocked endosomal entry by this virus. Thus, this anti-viral mechanism has evolved to work against many different viruses."

"We really don't understand the cellular mechanisms that block viral infections which has limited our ability to effectively respond to pandemics, including this year's coronavirus," said Lynda M. Stuart, M.D., Ph.D., Deputy Director, Bill & Melinda Gates Foundation, BRI Affiliate Investigator and co-author on the study. "We really need therapies that can block all viruses, including unknown future pathogens. To do that we need to find common pathways that viruses target and then develop approaches to block those vulnerabilities. Our work demonstrates one way in which cells can be modified to do this, and we hope that our insights will open up new avenues for scientists developing therapies and interventions to treat viral infectious diseases that impact millions of lives around the world."

The COVID-19 pandemic has dominated the news cycle for the better part of 2020. As guidelines are continually updated to reflect changes in our understanding of how the virus spreads, it is critical people receive accurate, credible information that encourages prevention. Understanding the factors that influence these messages' effectiveness is crucial.

A group of researchers published a paper in the American Journal of Preventive Medicine reporting their findings from a study funded by the Institute for Collaboration on Health, Intervention and Policy (InCHIP) at the University of Connecticut on how the source of a COVID-19 prevention message affects its perceived effectiveness.

This multi-institution project brought together the varied expertise of UConn Health's Howard Tennen, a professor of public health sciences in the School of Medicine, Marcella Boynton '05 (MA) '09 (PhD), an assistant professor at the University of North Carolina at Chapel Hill, Joseph Lee, an associate professor from East Carolina University, and Ross O'Hara, a former UConn Health postdoctoral fellow and independent researcher from Michigan.

The team conducted an experiment with a diverse group of nearly 1,000 American adults to test the effectiveness of different messages encouraging coronavirus safety measures such as wearing a mask or social distancing. Messages systematically varied in several ways, including who was attributed as the source of the message. Participants were told messages came from President Donald Trump, the Centers for Disease Control and Prevention (CDC), Trump and the CDC, a local or state health agency, or no source.

The team found when Trump's name was associated with the message, the effectiveness of those messages decreased, not just compared to other sources, but even when there was no source at all.

"Asking the public to restrict their behavior and social ties in such a big way is a difficult sell," Tennen says. "For these prevention messages to be believed, they have to come from a trusted source. We are in uncharted waters when it comes to effectively persuading people to wear masks and socially distance, and that's why we thought conducting this study was so important."

After receiving a postcard encouraging citizens to engage in social distancing and other prevention behaviors with Trump's name prominently featured, Boynton wondered whether this unusual messaging strategy was more effective compared to the traditional approach of citing a public health agency or organization as the message source.

Interestingly, the researchers found even participants who said they trust Trump did not find messages from him more effective compared to other message sources. However, those who said they do not trust the president found the messages significantly less effective when associated with Trump.

"Linking President Trump to prevention messages seems to work to the detriment of what those messages were trying to do," Boynton, who remains affiliated with InCHIP, says.

Boynton has a background in health behavior research and, with funding from the National Cancer Institute and Food and Drug Administration, had previously studied how to effectively communicate the health risks of tobacco use. She thought the current public health crisis called for the same kind of research methods to identify the best way to get credible, evidence-based prevention messages to the public.

These findings are important as various agencies and news outlets are trying to determine the best strategies to ensure these health messages are as effective as possible.

"A lot of the current prevention messaging efforts are just people's best guesses at what might work," Boynton says.

The team hopes to complete a follow up study examining how these types of messages affect people's engagement in prevention behaviors such as wearing a mask.

"I think behavioral science has a lot to contribute to stopping COVID-19, but so far, its potential has been underrealized and underutilized," Boynton says. "Until we have better treatments or a vaccine, a big part of stopping the spread of this disease is going to be about changing behavior."