Tech

New machine learning tool diagnoses electron beams in an efficient, non-invasive way

image: Artistic representation of a neural network superimposed on an electron beam profile.

Image: 
Adi Hanuka/SLAC National Accelerator Laboratory

Beams of accelerated electrons power electron microscopes, X-ray lasers, medical accelerators and other devices. To optimize the performance of these applications, operators must be able to analyze the quality of the beams and adjust them as needed.

For the past few years, researchers at the Department of Energy's SLAC National Accelerator Laboratory have been developing "virtual diagnostics" that use machine learning to obtain crucial information about beam quality in an efficient, non-invasive way. Now, a new virtual diagnostic approach, published in Scientific Reports, incorporates additional information about the beam that allows the method to work in situations where conventional diagnostics have failed.

"Our method can be used to diagnose virtually any machine that uses electron beams, whether it's an electron microscope for imaging of ultrasmall objects or a medical accelerator used in cancer therapy," said SLAC research associate Adi Hanuka, who led the study.

Conventional beam diagnostics are physical devices that need to interact with the beam to measure its properties, such as intensity and shape. This interaction often destroys or alters the beam or requires its deflection, so it cannot be used at the same time for the actual application. Technical limitations also prevent accurate measurements in some cases, for instance when the beam's electron pulses are fired at a very high rate or are very intense.

The new method has none of these limitations because it is not a physical device. Instead, it uses a neural network - a machine learning algorithm inspired by the neural network of the brain. Once the SLAC team had trained the neural network on data taken with the lab's particle accelerators, the algorithm was able to accurately predict beam properties for experimental situations.

The researchers demonstrated the method by comparing its predictions with experimental and simulated data for the electron beams of the Linac Coherent Light Source (LCLS) X-ray laser, its future upgrade LCLS-II, and the recently upgraded Facility for Advanced Accelerator Experimental Tests (FACET-II), three DOE Office of Science user facilities at SLAC.

In particular, the results show that the machine learning approach helps in situations that are beyond the capabilities of conventional tools. In the case of LCLS-II, for example, the neural network can provide detailed information about each of the million electron pulses per second the machine will produce - an unprecedented pulse rate that exceeds the limits of present diagnostic technology. Virtual diagnostics can also provide accurate information about FACET-II's high-intensity beam, which is challenging to analyze with physical devices.

Credit: 
DOE/SLAC National Accelerator Laboratory

Deadly heat waves will be common in South Asia, even at 1.5 degrees of warming

image: With 2 degrees Celsius of warming, the population of South Asia will experience more than double the exposure to unsafe labor temperatures (left) and will have almost three times the exposure to temperatures that cause lethal heat stress (right).

Image: 
Saeed et. al/ Geophysical Research Letters/AGU

WASHINGTON--Residents of South Asia already periodically experience heat waves at the current level of warming. But a new study projecting the amount of heat stress residents of the region will experience in the future finds with 2 degrees Celsius of warming, the population's exposure to heat stress will nearly triple.

Limiting warming to 1.5 degrees Celsius will likely reduce that impact by half, but deadly heat stress will become commonplace across South Asia, according to the new study in Geophysical Research Letters, AGU's journal publishing high-impact, short-format reports with immediate implications spanning all Earth and space sciences.

With almost one quarter of the world's population living in South Asia, the new study underlines the urgency of addressing climate change.

"The future looks bad for South Asia, but the worst can be avoided by containing warming to as low as possible," said Moetasim Ashfaq, a computational climate scientist at Oak Ridge National Laboratory and corresponding author of the new study. "The need for adaptation over South Asia is today, not in the future. It's not a choice anymore."

Earth has warmed by 1 degree Celsius since the start of the Industrial Revolution, according to the Intergovernmental Panel on Climate Change. On the current climate trajectory, it may reach 1.5 degrees Celsius of warming in 2040. This deadline leaves little time for South Asian countries to adapt. "Only half a degree increase from today is going to cause a widespread increase in these events," Ashfaq said.

A hot region getting hotter

People living in South Asia are especially vulnerable to deadly heat waves because the area already experiences very hot, humid summers. Much of the population live in densely populated cities without regular access to air conditioning, and about 60% perform agricultural work and can't escape the heat by staying indoors.

In the new study, the researchers used climate simulations and projections of future population growth to estimate the number of people who will experience dangerous levels of heat stress in South Asia at warming levels of 1.5 and 2 degrees Celsius. They estimated the wet bulb temperature residents will experience, which is similar to the heat index, as it takes into account humidity as well as temperature. A wet bulb temperature of 32 degrees Celsius (89.6 degrees Fahrenheit) is considered to be the point when labor becomes unsafe, and 35 degrees Celsius (95 degrees Fahrenheit) is the limit to human survivability - when the body can no longer cool itself.

Their analysis suggests at 2 degrees of warming, the population's exposure to unsafe labor temperatures will rise more than two-fold, and exposure to lethal temperatures rises 2.7 times, as compared to recent years.

Curbing warming to 1.5 degrees Celsius will likely cut that exposure in half, but large numbers of people across South Asia will still experience extreme temperatures. An increase in heat events that create unsafe labor conditions are likely to occur in major crop producing regions in India, such as West Bengal and Uttar Pradesh, and in Pakistan in Punjab and Sindh. Coastal regions and urban centers such as Karachi, Kolkata, Mumbai, Hyderabad and Peshawar are also likely to be heavily affected, according to the study.

"Even at 1.5 degrees, South Asia will have serious consequences in terms of heat stress," Ashfaq said. "That's why there is a need to radically alter the current trajectory of greenhouse gas emissions."

The results differ from a similar study conducted in 2017, which predicted that heat waves of lethal temperatures will occur in South Asia toward the end of the 21st century. The researchers suspect the earlier study is too conservative, as deadly heat waves have already hit the region in the past. In 2015, large parts of Pakistan and India experienced the fifth deadliest heat wave in the recorded history, which caused about 3,500 heat-related deaths.

"A policy framework is very much needed to fight against heat stress and heat wave-related problems," said T.V. Lakshmi Kumar, an atmospheric scientist at India's SRM Institute of Science and Technology who was not involved in the work. "India has already committed to reduce emissions to combat climate change issues."

The study was supported by National Climate?Computing Research Center, which is located within ORNL's National Center for Computational Sciences and supported under a Strategic Partnership Project between Department of Energy and National Oceanic and Atmospheric Administration.

Credit: 
American Geophysical Union

Automatic trail cameras keep wildlife research going during pandemic

video: A moose saunters into view of an automatic motion-activated trail camera, placed to passively monitor wildlife activity.

Image: 
Austin Green/University of Utah

For scientists, especially graduate students, who conduct fieldwork, every day is precious. Researchers meticulously prepare their equipment, procedures and timelines to make sure they get the data they need to do good science. So you can imagine the collective anxiety that fell across academia in spring 2020 when COVID-19 struck and many universities suspended in-person activities, including fieldwork.

But for Austin Green, a doctoral student in the School of Biological Sciences and 2019 recipient of a National Geographic Society Early Career Grant, who studies the wildlife that lives in the canyons of the Wasatch Front, that anxiety was tempered by the knowledge that pandemic or no pandemic, his network of automated motion-activated trail cameras would keep their silent watch over the canyons' mammals and birds.


Deer and wild turkeys.

"You can set them up at the beginning of the year and leave them up until your field season is over," Green says. "And we were not the only ones that did this. In fact, there were entire nationwide and global initiatives that were able to continue gathering data during pandemic restrictions on field research."

Now Green and his colleagues are sharing what they've learned about the importance of trail cameras for wildlife conservation and management in the journal Biological Conservation. As the COVID-19 pandemic has shown, they write, automatic trail cameras are good tools for a wide range of environments and research questions.

Watching the wildlife

Trail cameras (also called camera traps although they don't trap or restrain anything) are motion-activated cameras that researchers can attach to a tree or pole, usually at knee-height, in remote areas. The cameras then take photos whenever something walks by. Some models transmit photos wirelessly, but many collect photos on an SD card, which researchers like Green change out periodically when they change the camera's batteries. They can also be programmed to capture video to document fascinating vignettes of animal behavior.


Coyote.

"All newer models have exceptional battery life and photo storage capacity," Green says. "So, we set them up before restrictions went into place and kept them up throughout the entire field season, allowing us to gather another full season of data."

Even before the COVID-19 pandemic, biologists were already turning to trail cameras as a way to conduct biological surveys that avoided the difficult, labor-intensive process of physically trapping, tagging and releasing of animals.

"However, with trail cameras, researchers can monitor individual animals passively over a large number of cameras and a large area, as long as the individuals can be individually identified through photographs," Green says. "Cameras do not need to be maintained on a daily basis, and no individual animals ever need to be processed."

Inspiring volunteers

For Green's purposes, trail cameras are perfect. He's looking to study the wildlife that inhabit the canyons of the Wasatch Front, and with the help of a team of more than 200 community volunteers, maintains 300 trail cameras stretching as far north as Logan, Utah and as far south as  Point of the Mountain. The cameras have captured images of turkeys, herons, moose, coyotes, cougars and many others.

When COVID-19 restrictions began, Green quickly adapted his operation, moving training materials online and setting up a contactless pick-up method for equipment. Crowdsourced data entry proceeded as it had before. Green calls the efforts of his community volunteers inspiring.

"No matter what changes we threw at them, whether it was going completely online for all non-fieldwork related logistics or having to individually find time to disperse equipment, these amazing people never missed a beat," Green says. "One thing I'll take from this and apply to my research moving forward is that, even in hard times, there are always those willing to do what is necessary to get the job done."

And it was a good thing he and his volunteers were able to keep the cameras running, because the early weeks of the pandemic provided a unique research opportunity.

"The pandemic has created so much hardship and tragedy for so many people, and this can make it difficult to find any silver linings," Green says, "However, the sudden change in human traffic, deemed by scientists as the 'anthropause,' has presented an opportunity to study how wildlife react to quasi-experimental changes in human influence."

Çağan Şekercioğlu, associate professor in the School of Biological Sciences, says that trail cameras can also perform an important conservation function. While the general public, conservationists, rangers and others often had to stay home due to mandatory lockdowns, trespassers, poachers and illegal loggers continued going into wild areas. "During the lockdown, to this day in many places, trail cameras are our only eyes on the ground," Şekercioğlu says.

A range of research questions


A great blue heron wading in a stream.

Green, Şekercioğlu and colleagues write in Biological Conservation that trail cameras are well-suited for fundamental research questions like investigating the presence, relative abundance, density, occupancy, and activity of animal species. They can be instrumental in discovering the presence of a new species or the expansion of its range. Further, they write, while more cameras are better, even a single camera can yield valuable information.

Trail cameras can go further as well to address questions of human impacts on wildlife, trends in biodiversity, reproductive ecology, behavior and interactions between species, and even which predators are raiding bird nests.

As a research tool, trail cameras are a complement to good research design. "My advice for other researchers will always be to first and foremost clearly articulate the particular question they hope to address and decide what tools can be used to help them address it," Green says. "Although I'm not sure research can ever be fully 'pandemic-proofed' or resistant to disruptions, I can say that being willing, flexible and creative enough to adapt to unique situations will always be critical to the advancement of science. After all, so many great scientific discoveries were unexpected beforehand."

Credit: 
University of Utah

Henry Ford physician leads consensus for global awareness to an underrecognized condition

image: Dr. Craig has published nearly a dozen studies on the condition known as ODS in the last 2 years, which has culminated in an international consensus statement on diagnosing ODS (Feb. 2021), and a national consensus statement on treating ODS (July 2020).

Image: 
Henry Ford Health System

DETROIT (March, 23, 2021) - Henry Ford physician, John Craig, M.D., is leading an international research effort to improve the multidisciplinary collaboration between otolaryngologists and dental providers around the globe when it comes to diagnosing odontogenic sinusitis (ODS).

ODS is an infectious condition of the paranasal sinuses that can occur from either dental infection or dental procedures involving the upper jaw. There are multiple ways that infection can spread from the teeth to sinuses, and in more severe scenarios, to the eye, brain, or rest of the body. It has been shown that the various clinicians often needed to manage ODS, frequently miss the diagnosis.

Dr. Craig, a Henry Ford ear, nose and throat (ENT) surgeon who specializes in rhinology - the care and treatment of the sinuses and nasal cavities, recently led an international consensus statement for diagnosing ODS, in conjunction with Dr. Alberto Saibene from the University of Milan in Italy, and 15 other authors from around the world. The consensus statement was published in the International Forum of Allergy & Rhinology. The study's 17 authors included otolaryngologists and dental specialists from the U.S., Italy, Germany, Lithuania, France, Israel, Japan and Turkey. Authors were specifically selected for their expertise on ODS.

Dr. Craig explains that "what makes this medical consensus innovative and different is the international collaboration between rhinologists (sinus surgeons) and dental specialists (endodontists and oral surgeons) to achieve consensus on diagnosing ODS. The multidisciplinary nature was critical to highlight the importance of collaboration between ENT and dental providers to diagnose this condition."

Dr. Craig has researched ODS for the past 5 years and has published nearly a dozen studies on various aspects of ODS in the last 2 years. Now, he is spearheading an international effort to help inform the medical and dental communities.

"I had published studies on diagnostic features of ODS, but it takes a long time for individual studies to gain traction with clinicians. Dr. Saibene and Dr. Giovanni Felisati, from the University of Milan, had also been publishing on ODS in recent years, and they reached out to me. We clearly shared similar goals of increasing international awareness of this underrecognized condition," said Dr. Craig.

"We knew that one of the biggest hurdles to progress in this field was the lack of diagnostic criteria in our international sinusitis guidelines, which limits both research efforts and clinical care. It has been an honor working with such an amazing group of scientists, all who share a common passion for increasing awareness of ODS," said Dr. Craig.

Dr. Craig hopes the published international consensus statement will bring more peer attention to ODS globally, and that ODS diagnosis, as well as its management, can be included more thoroughly in future iterations of national and international sinusitis guidelines. He also hopes this information can be disseminated to all dental specialties through their respective guidelines as well. Improving awareness amongst otolaryngologists and dental specialists will hopefully improve collaboration between the two fields to diagnose this condition.

"In addition to increasing awareness internationally, it is of the utmost importance to implement our research findings on a local and regional level. To this end, we will continue to optimize care for these patients at Henry Ford and spread the word to our medical and dental communities in metro Detroit and Michigan," said Dr. Craig. His overriding message to clinicians is that "If you don't look for ODS, you'll often miss it. If you start looking for it, you'll be amazed how many patients you help."

Credit: 
Henry Ford Health

Highlands of diversity: Another new chameleon from the Bale region, Ethiopia

image: The new chameleon species, Trioceros wolfgangboehmei

Image: 
Koppetsch et al.

The Bale Mountains in south-central Ethiopia are considered to be one of the most unique centers of endemism, with an extraordinary number of plants and animals that can only be found there. Numerous species are already known from this Afromontane high-elevation plateau, making it a biodiversity hotspot, but ongoing research continues to reveal the presence of so far unknown and undescribed organisms.

Zoologists Thore Koppetsch and Benjamin Wipfler of the Research Museum Alexander Koenig in Bonn, Germany, and Petr Nečas from the Czech Republic, describe one such species: a new small-sized chameleon living on the edge of the forest. Their findings were published in the open-access, peer-reviewed life science journal Zoosystematics and Evolution.

There were already two species of the chameleon genus Trioceros known to be restricted to the Bale region when Thore Koppetsch and his colleagues discovered another unique representative of this group from the northern slopes of the Bale Mountains. Interestingly, this new chameleon is considered to be part of a species complex of the wide-spread Ethiopian Chameleon Trioceros affinis. Previous studies have indicated divergence between its different populations across the Ethiopian Highlands - with some of them separated by the northern extension of the Great Rift Valley, which also shaped the evolution of early humans.

The new chameleon, Trioceros wolfgangboehmei, has a special name. It honours the scientific work of Wolfgang Böhme, senior herpetologist at the Zoological Research Museum Alexander Koenig in Bonn, and his passion for chameleons and other reptiles.

Apart from its biogeographical patterns, the new species also has a characteristic appearance, displaying enlarged spiny scales on its back and tail that form a prominent crest. It usually lives on small trees and bushes at an altitude of above 2,500 m above sea level.

"Given the variation in colour patterns and morphology between different populations of these chameleons in Ethiopia, it is likely that these groups still bear a higher hidden diversity than expected, which might be revealed by further ongoing investigations" Thore Koppetsch notes. Furthermore, the research team urges for sustainable preservation and conservation of its habitat to mitigate the impact of human activity.

Credit: 
Pensoft Publishers

Changes in Antarctic marine ecosystems

image: The Antarctic peninsula is the most affected area by climate change in the white continent.

Image: 
Lluís Cardona (UB-IRBio)

Understanding the evolution of the polar sea ice is not enough to study the effects of the climate change on marine ecosystems in Antarctic seafloors. It is also necessary to determine the intensity of phytoplankton local production during the Antarctic summer, as stated in a new study by a research team of the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona, published in the journal Marine Environmental Research.

When the sea freezes in Antarctica

Extremely low temperatures, strong ocean currents and the broad seasonal coverage of marine ice are factors that determine the features of the Antarctic marine ecosystems. IN particular, the seasonality regarding the ice formation in the marine surface is a process that directly affects the dynamics of the marine ecosystems and the flow of matter and energy in complex Antarctic trophic networks. During the Antarctic winter, the ice and snow that accumulate limit the availability of light, and as a result, this reduces the activity of photosynthetic organisms and the production of krill (basic food resource within the food network in Antarctic marine ecosystems).

The main sources of organic carbon in Antarctic ecosystems located at the shallows are phytoplankton, algae that grow under the ice and algae that are stuck in rocks. However, great part of this primary production does not enter the trophic network directly through herbivores, but as detritus (particles of rock). "The presence of ice in the shallows limits the primary production during great part of the year. This determines that benthic trophic networks depend largely on the accumulated organic matter in seafloors during the summer months", notes Lluís Cardona, first author of the article and lecturer at the Department of Evolutionary Biology, Ecology and Environmental Sciences, and the IRBio.

"To date, we thought this dependence would be acute in areas where the sea surface remains frozen for a longer time, and this would involve a lesser diversity of trophic niches and a shorter and redundant trophic network while we go south", notes the researcher. The study highlights that the intensity of the summer bloom of phytoplankton alters this gradient and therefore the structure of coastal benthic systems is strongly modified wherever the bloom is intense.

Changes in Antarctic marine ecosystems

The study was based on the analysis of C and N stable isotopes to identify the ecological niche -the role of each organism in the structure and function of the ecosystem- of a series of marine species caught in Base Rothera, Cierva Cove, Maxwell Bay, Hope Bay, and Paradise Harbour, in the western side of the Antarctic peninsula, and Southern Shetland Islands. Using the isotopic analyses, experts could verify the great stability of the trophic level of each species but they also detected a considerable geographical variety in the used carbon sources. With the used methodologies in previous studies -in particular, the study of stomach content-, the obtained data provided a high taxonomic resolution but did not offer a complete version of the diet over time, which generated a great disparity in results.

According to the conclusions of the study, "where the phytoplankton production is intense, the benthic ecosystem receives lots of organic matter coming from the phytoplankton that becomes the basic source of carbon for benthic species, regardless of the latitude and length of the marine ice. This reduces the importance of benthic algae as a source of carbon, which is however very high since these are protected from herbivores by chemical defenses (repulsive natural products")", notes Lluís Cardona. Therefore, those areas that feature a summer bloom of intense phytoplankton, show a shorter and redundant trophic network, like in the sea surface that remains frozen for months. "Therefore, in order to assess the impact of climate change in benthic ecosystems, it is as much important to predict changes in summer production of phytoplankton as to simulate the length the ice will remain in the sea surface", notes the researcher.

A vulnerable polar region to climate change

The Antarctic peninsula is the most affected area by climate change in the white continent. According to current data, in winter, there is a reduction of the length of marine ice in the north, and a movement towards south regarding the species such as the Antarctic krill. Therefore, current conditions registered in the north of the Antarctic peninsula could be a model for the future of the southern-western peninsular areas as long as the summer production of phytoplankton remains the same, experts note.

Credit: 
University of Barcelona

Neutrons reveal unpredicted binding between SARS-CoV-2, hepatitis C antiviral drug

image: Neutron scattering experiments show that when telaprevir binds to the protease, the amino acid sites will change their electric charges by altering their protonation states.

Image: 
Jill Hemman and Michelle Lehman/ORNL, U.S. Dept. of Energy

Scientists have found new, unexpected behaviors when SARS-CoV-2 - the virus that causes COVID-19 - encounters drugs known as inhibitors, which bind to certain components of the virus and block its ability to reproduce.

Published in the Journal of Medicinal Chemistry, the research provides key insights for advancing drug design and drug repurposing efforts to treat COVID-19.

Researchers at the Department of Energy's Oak Ridge National Laboratory used neutron scattering to investigate interactions between telaprevir, a drug used to treat hepatitis C viral infection, and the SARS-CoV-2 main protease, the enzyme responsible for enabling the virus to reproduce.

They discovered unforeseen changes in the electric charges in the drug binding site of the protease enzyme that were not predicted by prevailing computer simulations.

"We found this particular protein - the SARS-CoV-2 main protease - which a lot of researchers are studying by computational methods, is behaving in a surprising way," said lead author Daniel Kneller. "Our findings provide critical experimental data needed to improve computer modeling so that simulations more closely match reality."

The virus reproduces by assembling long chains of proteins, or polyproteins, made from almost 2,000 amino acids that must be cut into smaller chains by the main protease. Finding a drug that effectively blocks or inhibits the protease function is paramount to preventing the virus from replicating and spreading to other healthy cells in the body.

In previous studies, the team used neutron and X-ray scattering to build a complete map of every atom in the SARS-CoV-2 protease enzyme. They located the sites where a drug inhibitor would bind to the protease enzyme and mapped the network of hydrogen bonds that hold the protease together. They also determined the locations of the positive, negative and neutral electric charges in the protease amino acid sites where the polyprotein cutting action occurs.

"In this study, we discovered that when telaprevir bound to the main protease, the protonation states [proton addition or loss] in the binding site altered, meaning the locations of the hydrogen atoms changed; essentially, some amino acid sites either gained or lost hydrogen atoms, which changed their electric charges," said ORNL corresponding author Andrey Kovalevsky.

"However, the overall electric charge of the protease inhibitor binding site remained the same as it was before it was attached to the drug molecule. That's something we didn't expect and wasn't correctly predicted in computer simulations."

The researchers said their observations suggest the protease enzyme can alter its protonation states when it binds to certain drugs, and therefore, assumptions about binding behaviors should not be based purely on the properties of the protease structure before an inhibitor is bound.

"Protein behavior at the level of individual atoms is notoriously difficult to predict. Simulations have to be designed based off ideal scenarios of general chemical knowledge and mathematics, but proteins don't always adhere to ideal scenarios," Kneller said.

Telaprevir is one of a number of FDA-approved drug inhibitors used to treat hepatitis C viral infection. It belongs to a class of agents called covalent peptidomimetic inhibitors that work by using strings of unnatural amino acids to bind to specific target proteins.

These inhibitors also include boceprevir and narlaprevir - two additional hepatitis C antiviral drugs the ORNL researchers studied in 2020 as potential drug repurposing candidates to treat COVID-19.

"We've shown that some of the hepatitis C virus protease inhibitors can also inhibit the SARS-CoV-2 main protease," said ORNL's Leighton Coates, the paper's co-corresponding author.

"In this study, we chose telaprevir because we were able to produce high-quality crystal samples that we could study with neutrons. This should have a direct impact on drug design.

"We believe what we learn from the interactions between telaprevir and the protease enzyme should be transferable to other covalent peptidomimetic inhibitors such as those being investigated right now by major pharmaceutical companies," Coates added.

Neutron scattering is the primary tool for scientific discovery in the team's ongoing research campaign into the SARS-CoV-2 main protease. Neutrons are uniquely suited to detect hydrogen atoms. They have no electric charge and are nondestructive, making them ideal probes for biological studies conducted at near-physiological temperature, such as this work.

Credit: 
DOE/Oak Ridge National Laboratory

Scientists observe complex tunable magnetism in a topological material

Scientists at the U.S. Department of Energy's Ames Laboratory have observed novel helical magnetic ordering in the topological compound EuIn2As2 which supports exotic electrical conduction tunable by a magnetic field. The discovery has significant implications for basic research into functional topological properties and may one day find use in a number of advanced technology applications.

Topological materials burst onto the scene in the physical sciences about fifteen years ago, decades after their existence had been theorized. Called 'topological' because their bulk electronic bands are "knotted" together, the surfaces of topological insulators "untie the knot" and become metallic. Researchers at the Ames Laboratory's Center for the Advancement of Topological Semimetals (CATS) are seeking to discover, understand, and control the exceptional conduction properties of these materials.

Much of modern technology relies on crystalline materials, which are solids composed of a repeating (periodic) arrangement of atoms that forms a lattice. Due to the periodicity, the lattice looks the same after certain symmetry operations such as translation, specific rotations, mirror, and/or inversion. The existence or absence of these symmetries affect electronic band topology and surface electronic conduction. Magnetic ordering can modify the symmetries exhibited by the material, providing an additional means to control the topological state.

In collaboration with scientists at Oak Ridge National Laboratory's Spallation Neutron Source, McGill University, and the University of Missouri Research Reactor Center, the CATS team discovered the existence of low-symmetry helical magnetic ordering in EuIn2As2 which supports a highly sought-after topological state called an axion insulator. This state shares similarities with the axion particle in quantum chromodynamics which is a candidate component of dark matter. In solid-state materials, it provides remarkable parallel coupling between magnetic and electrical properties.

In the presence of EuIn2As2's complex helical magnetic ordering, the axion state leads to topological features in the surface electronic spectrum called Dirac cones. When a Dirac cone occurs on a surface of the material penetrated by a fundamental axis of the magnetic ordering, the cone has no energy gap and the surface exhibits resistanceless conduction tied to the orientation of the electronic spin. The other surfaces have gapped Dirac cones and support half-integer quantized electrical conduction. The researchers predict that application of a relatively moderate magnetic field switches which surfaces support which type of Dirac cone, allowing the surface conduction to be tuned.

The ability to switch between surface states by a magnetic field provides an experimental avenue to examine the unique properties of its topological states. This tunability is also promising for technologies such as high-precision sensors, resistanceless nanowires, magnetic storage media, and quantum computers. Future studies will look at bulk crystals while applying a magnetic field and will synthesize and study nanoscale-thin films in order to pave the way for technological applications.

Credit: 
DOE/Ames National Laboratory

North American deserts are a biodiversity hotspot for butterflies

image: This image shows Chandra Earl looking at butterfly specimens.

Image: 
Chandra Earl

By comparing the genetic diversity of butterflies in North America, researchers reporting in the journal iScience on March 23 found that the array of different evolutionary distinct groups of butterflies is particularly high in the deserts of Mexico and the southwestern United States. This may be an outcome of actively changing conditions in the Desert Southwest and more generally in the western portion of the continent.

"When you think of desert, you don't automatically jump to butterflies, but our results showed that this area is actually a really important hotspot for butterflies, even if it isn't for plants," says co-first author Chandra Earl, who recently received her PhD from the University of Florida. "Just because butterflies are closely tied to their host plants doesn't mean their diversity outcomes have to be similar."

To do their continent-wide analysis, the researchers utilized a variety of biodiversity repositories, including GenBank, Barcode of Life Data System (BOLD), and Map of Life (@moldotorg). However, instead of just counting the butterfly and plant species in an area, the researchers tracked phylodiversity, which also considers the degree of evolutionary relatedness between species in that area. This can reveal patterns that counting species does not, because a group of disparate species will show more phylodiversity than if they were closely related.

"We wouldn't have found the same result if we'd just counted the species like most biodiversity studies." says Earl, also of the Florida Museum of Natural History. "But we really wanted to step away from that, so we didn't lose the importance of evolutionary history."

Why butterflies show more phylodiversity than plants in the desert may have to do with how they interact in the ecosystem.

"Most butterflies are generalists that don't utilize just one host plant. This means that there are a lot of plants with no real functional relevance to butterflies" says other co-first author Michael Belitz, a PhD candidate in Biology at the University of Florida. "This makes butterflies less likely to clump into groups of tightly related species like plants do."

Other ecological factors may come into play as well, such as the fact that butterflies are much more mobile than plants. While seed plant species clump together by virtue of sharing an inescapable habitat, especially in the desert where water is scarce, butterflies are free to roam.

"These factors all add noise to the data, where you won't see as strong a relationship between plants and butterflies as you might expect," says Belitz.

While there is still much to learn about the relationship between butterflies and plants, this project opens up new avenues for biodiversity research by comparing groups of species on a large scale instead of focusing on a single group.

"These methods of comparing groups are actually really young," says Belitz. "It's really an open arena."

As for the butterflies, the researchers hope that this new understanding of their biodiversity will encourage others to research and conserve these insects.

"People already know about the decline of monarch butterflies, but the entire group is under threat," says Earl. "We need to start paying better attention to insects, and this study helps prioritize North American deserts as a new target for conservation efforts."

Credit: 
Cell Press

CHOP researchers find supplement prevents strokes in patients with rare genetic disorder

Philadelphia, March 23, 2021 - Researchers from Children's Hospital of Philadelphia (CHOP) have discovered that a widely used nutritional supplement may significantly reduce the risk of fatal strokes caused by a rare genetic disorder. Additionally, the findings suggest that the supplement could be used to both block precipitation of and break up the formation of amyloid plaque deposits, a common feature found in serious forms of dementia. The findings were published online today by the journal Nature Communications.

The findings centered around a genetic disorder known as hereditary cystatin C amyloid angiopathy (HCCAA). HCCAA is part of a group of diseases in which amyloid proteins build up and deposits form on the walls of blood vessels in the central nervous system. Most people with the leucine to glutamine variant of hCC (L68Q-hCC) that causes this disorder suffer strokes and brain hemorrhages in their 20s, leading to paralysis, dementia and death as these strokes become more frequent. The amyloid deposits observed in cases of HCCAA are implicated in a wide range of neurodegenerative diseases, including Alzheimer's, Parkinson's, Creutzfeldt-Jacob's and Huntington´s diseases.

"While this is a rare disease, most patients diagnosed with HCCAA die within five years of their first stroke, so there is an incredible need to study this genetic disorder and find effective treatment options," said Hakon Hakonarson, MD, PhD, Director of the Center for Applied Genomics at CHOP and lead author of the study.

Since the formation of amyloid-producing proteins is already implicated in HCCAA and other diseases, researchers have studied whether drugs that reduce the aggregation of these proteins have the potential to reduce the toxic oligomers, or polymers made up of a few different molecules. To properly study this strategy in HCCAA, the research team created cell lines expressing both wild type and L68Q-mutant hCC and then attempted to non-toxically interfere with the aggregation of the amyloid-producing proteins. The researchers also studied a supplement called N-acetyl-cysteine (NAC), which is sometimes prescribed to break up mucous in the lung and has also been shown to protect against the toxic liver damage caused by an acetaminophen overdose, to determine whether it had an effect on hCC-amyloid protein deposits in skin biopsies of patients with a known diagnosis of HCCAA.

The researchers found that treating these cell lines with NAC breaks the oligomers into monomers, or molecules that have been separated from the chain that brings them together. This in turn helps to prevent the formation of amyloid-producing proteins that lead to the amyloid deposits implicated in strokes and other impairments. The researchers also performed skin biopsies on six patients with the L68Q-hCC variant taking NAC to determine levels of hCC-amyloid protein deposits following treatment. Five of the six patients saw between a 50% and 90% reduction of L68Q-hCC levels, suggesting that this variant is a clinical target for reducing agents such as NAC. This proof-of-concept study led to a clinical trial to see if these results are observed in a larger patient cohort.

"Amyloids cannot precipitate without aggregating, so if we can prevent that aggregation with a drug that is already available, then we could make an incredible difference in the lives of these patients," Hakonarson said. "Additionally, since we already have genetic testing available to identify these patients, we could conceivably give this treatment early in life and potentially prevent that first stroke from ever occurring."

Credit: 
Children's Hospital of Philadelphia

Algorithms inspired by social networks reveal lifecycle of substorms, a key element of space weather

image: Map representing a snapshot of the community structure at onset.

Image: 
Background map SuperMAG

Evolution of auroral substorms revealed by physicists at University of Warwick using the same methods that link people through social media

'If you like this magnetometer, you might like this one too:' historical data from magnetometers used to match them with 'like-minded friends' during 41 substorms

Shows that a single coherent electrical current, that accompanies the Northern Lights during substorms, covers most of the Earth's night-side at high latitudes

Will help to validate models used to predict auroral substorms, which can disrupt electronics and power distribution systems

Space weather often manifests as substorms, where a beautiful auroral display such as the Northern Lights is accompanied by an electrical current in space which has effects at earth that can interfere with and damage power distribution and electrical systems. Now, the lifecycle of these auroral substorms has been revealed using social media-inspired mathematical tools to analyse space weather observations across the Earth's surface.

Analysis by researchers led by the University of Warwick has revealed that these substorms manifest as global-scale electrical current systems associated with the spectacular aurora, reaching across over a third of the globe at high latitudes.

New research which involves the University of Warwick, John Hopkins University - Applied Physics Laboratory, University of Bergen and Cranfield University, and published today (23 March) in the journal Nature Communications processes data on disturbances in the Earth's magnetic field from over a hundred magnetometers in the Northern hemisphere using a new technique that enables them to find 'like-minded friends'.

Magnetometers register changes in the Earth's magnetic field. When charged particles from our Sun bombard the Earth's magnetic field, it stores up energy like a battery. Eventually, this energy is released leading to large-scale electrical currents in the ionosphere which generate disturbances of magnetic fields on the ground. At extremes, this can disrupt power lines, electronic and communications systems and technologies such as GPS.

Using historical data from the SuperMAG collaboration of magnetometers, the researchers applied algorithms from network science to find correlations between magnetometer signals during 41 known substorms that occurred between 1997-2001. These use the same principles that allow a social networking site to recommend new friends, or to push relevant advertisements to you as you browse the internet.

Magnetometers detecting coherent signals were linked into communities, regardless of where they were located on the globe. As time progressed, they saw each substorm develop from many smaller communities into a single large correlated system or community at its peak. This led the authors to conclude that substorms are one coherent current system which extends over most of the nightside high latitude globe, rather than a number of individual small and disjointed current systems.

Dr Lauren Orr, who led the research as part of her PhD at the University of Warwick Department of Physics and is now based at Lancaster University, said: "We used a well-established method within network science called community detection and applied it to a space weather problem. The idea is that if you have lots of little subgroups within a big group, it can pick out the subgroups.

"We applied this to space weather to pick out groups within magnetometer stations on the Earth. From that, we were trying to find out whether there was one large current system or lots of separate individual current systems.

"This is a good way of letting the data tell us what's going on, instead of trying to fit observations to what we think is occurring."

Some recent work has suggested that auroral substorms are composed of a number of smaller electrical current systems and remain so throughout their lifecycle. This new research demonstrates that while the substorm begins as lots of smaller disturbances, it quite rapidly becomes a large system over the course of around ten minutes. The lack of correlation in its early stages may also suggest that there is no single mechanism at play in how these substorms evolve.

The results have implications for models designed to predict space weather. Space weather was included in the UK National Risk Register in 2012 and updated in 2017 with a recommendation for more investment in forecasting.

Co-author Professor Sandra Chapman adds: "Our research introduces a whole new methodology for looking at this data. We've gone from a data poor to a data rich era in space plasma physics and space weather, so we need new tools. It's a first to show that you can take one of these tools to our field and get a really important result out of it. We've had to learn a lot to be able to do that, but in doing so it opens up a new window into the data."

Credit: 
University of Warwick

Novel thermometer can accelerate quantum computer development

image: The new quantum thermometer on a chip, in the foreground. It is probably the world's fastest and most sensitive thermometer for measuring temperature at the cold end of a waveguide at the millikelvin scale, according to the Chalmers researchers.

Image: 
Claudia Castillo Moreno/Chalmers University of Technology

Researchers at Chalmers University of Technology, Gothenburg, Sweden, have developed a novel type of thermometer that can simply and quickly measure temperatures during quantum calculations with extremely high accuracy. The breakthrough provides a benchmarking tool for quantum computing of great value - and opens up for experiments in the exciting field of quantum thermodynamics.

A key component in quantum computers are coaxial cables and waveguides - structures which guide waveforms, and act as the vital connection between the quantum processor, and the classical electronics which control it. Microwave pulses travel along the waveguides to the quantum processor, and are cooled down to extremely low temperatures along the way. The waveguide also attenuates and filters the pulses, enabling the extremely sensitive quantum computer to work with stable quantum states.

In order to have maximum control over this mechanism, the researchers need to be sure that these waveguides are not carrying noise due to thermal motion of electrons on top of the pulses that they send. In other words, they have to measure the temperature of the electromagnetic fields at the cold end of the microwave waveguides, the point where the controlling pulses are delivered to the computer's qubits. Working at the lowest possible temperature minimises the risk of introducing errors in the qubits.

Until now, researchers have only been able to measure this temperature indirectly, with relatively large delay. Now, with the Chalmers researchers' novel thermometer, very low temperatures can be measured directly at the receiving end of the waveguide - very accurately and with extremely high time resolution.

"Our thermometer is a superconducting circuit, directly connected to the end of the waveguide being measured. It is relatively simple - and probably the world's fastest and most sensitive thermometer for this particular purpose at the millikelvin scale", says Simone Gasparinetti, Assistant Professor at the Quantum Technology Laboratory, Chalmers University of Technology.

Important for measuring quantum computer performance

The researchers at the Wallenberg Centre for Quantum Technology, WACQT, have the goal to build a quantum computer - based on superconducting circuits - with at least 100 well-functioning qubits, performing correct calculations by 2030. It requires a processor working temperature close to absolute zero, ideally down to 10 millikelvin. The new thermometer gives the researchers an important tool for measuring how good their systems are and what shortcomings exist - a necessary step to be able to refine the technology and achieve their goal.

"A certain temperature corresponds to a given number of thermal photons, and that number decreases exponentially with temperature. If we succeed in lowering the temperature at the end where the waveguide meets the qubit to 10 millikelvin, the risk of errors in our qubits is reduced drastically", says Per Delsing, Professor at the Department of Microtechnology and Nanoscience, Chalmers University of Technology, and leader of WACQT.

Accurate temperature measurement is also necessary for suppliers who need to be able to guarantee the quality of their components, for example cables that are used to handle signals down to quantum states.

New opportunities in the field of quantum thermodynamics

Quantum mechanical phenomena such as superposition, entanglement and decoherence mean a revolution not only for future computing but potentially also in thermodynamics. It may well be that the thermodynamic laws somehow change when working down at the nanoscale, in a way that could one day be exploited to produce more powerful engines, faster-charging batteries, and more.

"For 15-20 years, people have studied how the laws of thermodynamics might be modified by quantum phenomena, but the search for a genuine quantum advantage in thermodynamics is still open", says Simone Gasparinetti, who recently started his own research group and plans to contribute to this search with a novel range of experiments.

The new thermometer can, for example, measure the scattering of thermal microwaves from a circuit acting as a quantum heat engine or refrigerator.

"Standard thermometers were fundamental for developing classical thermodynamics. We hope that maybe, in the future, our thermometer will be regarded as pivotal for developing quantum thermodynamics", says Marco Scigliuzzo, doctoral student at the Department of Microtechnology and Nanoscience, Chalmers University of Technology.

Credit: 
Chalmers University of Technology

Scientists created edible food films for food packaging

image: Rammohan Aluru and Grigoriy Zyryanov ones on scientists group, who have developed edible food films based on seaweed (stripped off solution of ferulic acid and sodium alginate in a Petri dish).

Image: 
UrFU / Andrey Fomin.

An international group of scientists from India and Russia has created edible food films for packaging fruits, vegetables, poultry, meat, and seafood. Films consist of natural ingredients, they are safe for health and the environment. In addition, films are water-soluble and dissolve by almost 90% in 24 hours. Description of the research and results of experiments are published in the Journal of Food Engineering.

"We have created three types of food films based on the well-known naturally occurring seaweed biopolymer sodium alginate," said Rammohan Aluru, senior researcher Organic synthesis laboratory at Ural Federal University and co-author of the paper. "Its molecules have film-forming properties. Sodium alginate is an auspicious carbohydrate macromolecule that has the potential film-forming properties upon hydrolysis and abundantly existed in cell walls as a mixture of various salts. The greatest advantage of sodium alginate is that it performs as liquid-gel in an aqueous medium."

Alginate molecules were cross-linked with a natural antioxidant ferulic acid. It makes the film not only strong, but also homogeneous, more rigid, and prolongs the life of the products.

"Food stays fresh longer due to the antioxidant components that slow down the oxidation processes," said Grigory Zyryanov, professor of the Department of Organic and Biomolecular Chemistry at Ural Federal University. "In addition, we can add to the films natural antiviral agents, that will also extend the shelf life of food. Garlic, turmeric, and ginger contain compounds that may prevent the spread of the viruses."

According to the authors, no special equipment for the production of films is required. On an industrial scale, it can be created by food products and films manufacturers.

"It can also be produced at a polymer production plant. The only condition is that it must meet the standards that apply to food production. And if an inexhaustible source of algae the ocean is nearby it will be quite simple to create such films," said Grigory Zyryanov.

Credit: 
Ural Federal University

Virtual pollination trade uncovers global dependence on biodiversity for food consumption

image: Virtual Pollination Flow from developing countries to Europe, North America, and Japan.

Image: 
Karlo Guidoni-Martins

Recently, a published study in Science Advances assessed the contribution of pollinators to international market flows and showed that biodiversity conservation is essential to sustain global consumption patterns. This study results from the work of an interdisciplinary team that integrated researchers across the fields of economics, ecology, environmental sciences and social sciences.

Given the growing global demand for crops, sustainability in agriculture is one of the main challenges for human society. Together with the excessive use of chemical inputs, the loss of natural habitat associated with cropland expansion is one of the main drivers of biodiversity decline, and more specifically of pollinator decline. Since pollinators (especially insects) contribute to the production of the vast majority of crops, biodiversity loss negatively impacts crop yield. Quality of the crop product can also be affected, biotic pollination improving the nutritional content and aesthetic appearance associated with the crop market value).

Inspired by the concept of Virtual Water Flow, which measures the amount of water associated with crop products traded in international markets, the concept of Virtual Pollination Flow was defined in this paper as the proportion of exported products resulting from pollinator action. Felipe Deodato (Federal Instituto of Mato Grosso - IFMT, Brazil), who together with Luísa Carvalheiro (Federal University of Goiás - UFG, Brazil) led this research, said that "the concept of Virtual Pollination Flow shows how global markets, particularly those associated with more developed countries, are excessively demanding of pollination services from developing countries." For example, Europe and the United States are heavy consumers of pollination services from Brazil via pollinator-dependent crops, such as coffee, soybeans, oranges, apples, watermelons, mangos, and avocados.

The study also showed that less-developed countries (i.e. those scored lower on the Human Development Index) are those that most expanded their cropland area dedicated to pollinator-dependent crops. This expansion was associated with loss of those pollinators' natural habitat. Luísa Carvalheiro (UFG) warned that "yield loss associated with decreased ecosystem services, such as crop pollination, stimulates even more cropland expansion, thus creating a vicious circle with negative effects for both biodiversity and agriculture".

The authors also pointed out the socioeconomic consequences of this trend. Small scale farmers, who are responsible for a significant portion of crop production worldwide, are those with less capacity to deal with crop yield losses.

Frédéric Mertens (University of Brasília - UnB, Brazil) emphasized that "the interdisciplinary approach of this research revealed the need to develop strategies of global collaborative governance that goes beyond economic principles of free markets, and instead aims for a synergy between international crop markets, biodiversity conservation and social justice".

Although many previous studies reported pollinator declines and highlighted their important role in agriculture, the general public is still largely unaware of the impacts of the current agribusiness model and associated international markets on biodiversity. "When the consumers buy a package of coffee, they know where it came from just by looking at the label, but they don't know if the farmer used sustainable practices to safeguard insects that pollinated coffee
production", said Felipe Deodato. The researchers hope that, by facilitating the identification of global economic connections mediated by ecosystem services, the work will stimulate a recognition of shared responsibility, in which all participants in the production process (farmers, consumers and politicians) are engaged to minimize environmental impacts.

Credit: 
Universidade de Brasília

Variances in critical protein may guide fate of those infected with SARS CoV-2

image: Graphic showing the chain of events when a cell is infected with a virus like SARS CoV-2. Within a living cell, proteins derived from pathogens like viruses are cut into fragments in the proteosome. These fragments then migrate through a series of cell structures, including the endoplasmic reticulum and the Golgi apparatus. When these peptide fragments bind with the MHC-I complex, they can be presented to CD+8 T cells at the cell surface. Should CD+8 T cells determine that the peptides belong to an alien entity like a virus, they will kill the cell to help stop the spread of viruses to other cells. This is an essential component of the adaptive immune response.

Image: 
Graphic by Shireen Dooling The Biodesign Institute at Arizona State University

Of the many perplexing questions surrounding SARS CoV-2, a mysterious new pathogen that has killed an estimated 2.6 million people worldwide, perhaps the most insistent is this: why does the illness seem to strike in such a haphazard way, sometimes sparing the 100 year old grandmother, while killing healthy young men and women in the prime of life?

A new study by Karen Anderson, Abhishek Singharoy and their colleagues at the Biodesign Institute at Arizona State University, may offer some tentative clues. Their research explores MHC-I, a critical protein component of the human adaptive immune system.

The research suggests that certain variant forms of MHC-I can help protect the body, by stimulating a strong immune response, while others may leave an individual susceptible to viral assault, severe illness and possibly, death.

"The implication of our findings is that the capacity to mount a strong and diverse T cell response to SARS-CoV-2 may be important to limit disease severity," Anderson says. "The key to this work is using protein structure to predict individual MHC-I peptide binding capacity."

Anderson is researchers at the Biodesign Virginia G. Piper Center for Personalized Diagnostics and professor at ASU's School of Life Sciences. Singharoy is a researcher in the Biodesign Center for Applied Structural Discovery and assistant professor at ASU's School of Molecular Sciences.

Cellular police

Humans, like all vertebrates, carry MHC-I molecules in all nucleated cells. A central role of MHC-I is to help the body clear infections from viruses and other pathogens. It does this by gathering fragments of the virus, ferrying them to the cell surface and presenting them to immune agents known as CD8+ T cells, which ceaselessly patrol the body.

MHC-I however, is a polymorphic molecule, meaning that it occurs in a wide variety of forms, which differ markedly in their ability to bind viral fragments and present them for interrogation by T cells. Depending on which MHC-I variants or alleles are present, the body may mount a successful immune response to SARS CoV-2, or may fail to do so, leaving the body vulnerable.

In new research appearing in the journal Cell Reports Medicine, Anderson, Singharoy and their colleagues describe a sophisticated algorithm known as EnsembleMHC, designed to predict which MHC-I alleles are best at binding viral fragments and presenting them to T cells. They also identify 108 viral peptides derived from SARS CoV-2 structural proteins, believed to be potent stimulators of the immune response.

"This is one of the first examples of molecular epidemiology with the SARS-CoV2 spike," says Singharoy. The scaling from molecular properties to population properties, developed by (first author) Eric Wilson is quite novel."

Wilson is a researcher at the Biodesign Institute and ASU's School of Molecular Sciences.

Range of effects

The research examines 52 common MHC-I alleles and finds significant disparities in their ability to bind viral fragments derived from the full SARS CoV-2 genome as well as fragments derived from a key subset of structural components believed to be the most important viral proteins for generating robust immune responses. These essential proteins help the virus assemble 4 critical structures and are known as the S (Spike), N (Nucleocapsid), M (Membrane), and E (Envelope) proteins.

CD8+ T cells are able to recognize docking regions on these structural proteins, known as epitopes. When these patrolling immune cells encounter S, N, M and E proteins, they will usually target the infected cell for destruction.

When the researchers compared COVID-19 figures from 23 countries, they found that mortality rates from the disease were closely associated with the distribution of MHC-I variants. Specifically, populations rich in MHC-I alleles ranked as strong binders of SARS CoV-2 peptide fragments showed reduced rates of death from COVID-19, suggesting these favorable MHC-I alleles generate a robust immune response when they encounter the novel coronavirus.

The work has important implications for monitoring vulnerability to COVID-19 in both individuals and populations and can also help researchers ferret out the essential pieces of the SARS CoV-2 pathogen that best stimulate the immune response, a critical component in future vaccines.

Defensive measures

MHC-I molecules are generated by the MHC gene, which is the most polymorphic part of the entire human genome. MHC is known to encode over 160 proteins of diverse function, half of which are directly involved in immune responses. The enormous diversity of MHC-I proteins provide the body with a formidable early warning defense system, capable of binding a broad range of pathogen fragments and fine-tuning the immune response. The rich diversity of MHC-I molecules also makes it difficult for a foreign invader like a virus to stealthily outwit all of the potential binding molecules.

The CD8+ T cells conducting their surveillance have an uncanny ability to distinguish self from non-self. If the T cells don't like what they see, when antigen-presenting MHC-I molecules display the fragments they have acquired, the CD8+ T cells will terminate the infected cell.

Previous research has shown that even slight amino acid variances in MHC-I composition can have profound effects. On the one hand, some MHC-I forms may promote inflammatory and autoimmune diseases, such as Graves's disease, psoriasis, rheumatoid arthritis, or multiple sclerosis, in which healthy tissues are recognized as foreign. On the other hand, MHC-I variants may be structurally unequipped to bind the proper fragments of a virus or other pathogen and fail to mount an immune response. For this reason, MHC genotype is considered a critical determinant of patient outcomes following a range of viral infections.

MHC-I also plays an important role in cases of tissue transplantation, as its full name--major histocompatibility complex--suggests. If donated tissue is not compatible with the recipient, MHC-I molecules present fragments from the donor tissue, which are recognized as foreign and attacked by T cells, a phenomenon known as graft-host rejection, another form of autoimmunity.

Following the trail of protection

In the current study, researchers examined 52 common alleles of the MHC-I protein, using a custom-designed algorithm known as EnsembleMHC to predict their binding affinities for SARS CoV-2 protein fragments. Two sets of data were compiled, the first, measuring each allele's binding affinity for the complete repertoire of proteins in the SARS CoV-2 genome. The second data set examines the binding affinities of each allele to just the S, N, M and E structural viral peptide candidates.

The researchers then mined a massive data bank of protein alleles, matching the prevalence of the 52 alleles in the study with 23 counties. Each country received a population-wide score, which combines the MHC-I binding capacity with MHC-I allele frequencies.

A compelling correlation was found between countries with lower mortality rates during the January-April, 2020 study period and high population-wide percentages of alleles identified by EnsembleMHC as strong binding molecules for SARS CoV-2 proteins.

Further, when only those alleles exhibiting high binding affinity for the S, N, M, and E proteins were compared, the association between low COVID-19 mortality and this suite of favorable MHC-I alleles was strongest, again suggesting that the virus's structural proteins are the most effective in producing an immune response.

The findings suggest that patients who have MHC-I alleles capable of engaging with SARS-CoV-2 structural protein peptides may stimulate an enhanced CD8+ T cell response, with improved post-infection outcomes and lower mortality.

The powerful technique described in the new study further unveils the subtle relationship of MHC-I alleles and immune response and will help researchers pinpoint the most important immunogenic viral fragments from SARS CoV-2, aiding future vaccine development. Combining such information with patient clinical data and genetic profiles may help identify those at greatest risk for this still-elusive disease.

Credit: 
Arizona State University