Culture

Blood clots and lung injuries found in patients who have died of COVID-19 

Ten post-mortem examinations performed on patients with confirmed COVID-19 found that all patients had lung injuries and early scarring of the lungs as a result of the virus, as well as injury to their kidneys.  Nine patients also had thrombosis - a blood clot- in at least one major organ (heart, lung or kidney). The team were unable to investigate thrombosis in the tenth patient.  

The research team behind the study believe that the findings could help guide clinicians on treating complications as a result of COVID-19, such as using blood thinners to prevent blood clots from developing.  They also hope that better understanding of the key complications in severe cases could help clinicians develop new ways to monitor and treat the disease. 

The study, published in The Lancet Microbe, was led by researchers at Imperial College London and Imperial College Healthcare NHS Trust.  Although the numbers of patients examined is small, this is the largest study to date of post-mortem examinations on COVID-19 patients in England.

Dr Michael Osborn, Honorary Clinical Senior Lecturer at Imperial College London, Consultant Pathologist at Imperial College Healthcare NHS Trust and co-author of the study, said:
"COVID-19 is a new disease and we have only had limited opportunities to comprehensively analyse tissues from patients at autopsy, to better understand what caused a patient's illness and death for research purposes.  Our study is the first of its kind in the country to support existing theories from researchers and doctors on the wards that lung injuries, thrombosis and immune cell depletion are the most prominent features in severe cases of COVID-19.  In the patients we looked at, we also saw evidence of kidney injuries and in some cases pancreatitis and these with our other findings will help clinicians develop new strategies to manage patients.  ??"Autopsy based analysis of COVID-19 for research is vital to learn more of this disease as the pandemic develops. We are extremely grateful to those who consented to this research and appreciate the advancement of medical science their generosity will bring.  

As a result of our work, we have worked with colleagues at the Royal College of Pathologists to produce national guidelines for autopsies in COVID-19 patients and in anticipation of a possible second wave of cases we have put systems in place to rapidly facilitate further studies in the future and so further our understanding on the nature and cause of the disease, which we hope would lead to more effective treatments and fewer deaths."

Dr Brian Hanley, from the Department of Cellular Pathology at Imperial College Healthcare NHS Trust and co-author of the study, added:

"The UK has sadly had a large number of deaths related to COVID-19. The search for effective treatments will rely on an understanding of how the disease affects the body. The post-mortem examination is vital in this respect. The findings in this study support research from other autopsy groups worldwide and in the UK that describe the structural damage to organs caused by COVID-19. It also documents several unexpected complications.  This increased understanding of COVID-19 can help clinical teams with the management of severe cases and also to monitor and treat further complications as a result of the disease."

During the lockdown period researchers nationally had very limited opportunities to carry out post mortem examinations for research purposes on patients who died from the disease.  The team wanted to see whether they can glean new insights on how the virus infects the cells of the body by studying tissue samples from patients who died as a result of severe COVID-19.

The team performed full post-mortem examinations and biopsies on ten patients aged 22-97 at Imperial College Healthcare NHS Trust hospitals during March-June. Full consent for post mortem with widespread tissue sampling and use of the tissue for research was sought from the relatives and friends of the deceased in line with national protocols. Seven of the patients were men and four were women.  Six of the patients were from a BAME background and four patients were white.

In the patients studied, high blood pressure and chronic obstructive pulmonary disease - the name for a group of lung conditions that cause breathing difficulties - were the most common contributing factors to death.  All patients developed a fever and had at least two respiratory symptoms such as cough and shortness of breath during the early stages of the disease.  Most patients died within three weeks of presenting with symptoms and treatments varied across the cohort.

The study team also reported six main findings:

All patients had diffuse alveolar damage (DAD).  DAD is a term used to describe a pattern of lung injury which can be seen as a result of viral infection.  This type of lung injury can affect both gas exchange (oxygen and carbon dioxide) and blood flood in the lungs. 
 

All patients fully assessed Nine of the ten patients had some form of thrombosis- blood clot - in at least one major organ (it was not possible to investigate thrombosis in the tenth patient).  Thrombosis prevents blood from flowing normally through the circulatory system and can lead to strokes and heart attacks.  The researchers found thrombi in the lungs of eight patients, the heart of five patients and the kidneys of four patients. They believe that this supports the theory that COVID-19 causes circulatory complications and that patient treatment could be augmented with blood thinning medication to prevent blood clots
 

All patients had evidence of acute renal tubular injury - a kidney injury that can lead to kidney failure or damage.  The main causes are low blood flow to the kidneys and severe infections.  It often affects patients who are in hospital and intensive care units
 

T-Lymphocyte Depletion (TLD) in the spleen and the lymph nodes was another consistent finding.  T-lymphocytes (white blood cells) are a major component of the immune system and play a role in destroying infections.  TLD is a reduction in T-lymphocytes, which alters the immune system and its response.  Haemophagocytosis is another consistent finding in this group, which occurs when the immune system overreacts to an infection and destroys some of its own cells
 

The researchers found evidence of acute pancreatitis in two of the patients.  Acute pancreatitis is a condition where the pancreas becomes inflamed.  It can be treated with fluids into the veins but in some cases can develop into serious complications and cause organ failure.  Damage to the pancreas in COVID-19 patients has not been reported before but it is not clear in this study whether the pancreatitis was related to COVID-19 infection or other causes
 

The researchers also found evidence of a rare fungal infection, in one of the patients, called Mucormycosis. Mucormycosis is an infection that may spread through the bloodstream to affect another part of the body. Severe infections can involve the lungs, brain and other organs including the kidneys, spleen and heart.

The team is working with a range of research groups both nationally and internationally to perform more detailed analyses of these tissues and is hoping that this research will expand to include a wider range of patients. 

Credit: 
Imperial College London

Research shows air pollution could play role in development of cardiometabolic diseases

Air pollution is the world’s leading environmental risk factor, and causes more than nine million deaths per year. New research published in the Journal of Clinical Investigation shows air pollution may play a role in the development of cardiometabolic diseases, such as diabetes. Importantly, the effects were reversible with cessation of exposure.

 

Researchers found that air pollution was a “risk factor for a risk factor” that contributed to the common soil of other fatal problems like heart attack and stroke. Similar to how an unhealthy diet and lack of exercise can lead to disease, exposure to air pollution could be added to this risk factor list as well.  

 

“In this study, we created an environment that mimicked a polluted day in New Delhi or Beijing,” said Sanjay Rajagopalan, MD, first author on the study, Chief of Cardiovascular Medicine at University Hospitals Harrington Heart and Vascular Institute, and Director of the Case Western Reserve University Cardiovascular Research Institute. “We concentrated fine particles of air pollution, called PM2.5 (particulate matter component < 2.5 microns). Concentrated particles like this develop from human impact on the environment, such as automobile exhaust, power generation and other fossil fuels.”

 

These particles have been strongly connected to risk factors for disease. For example, cardiovascular effects of air pollution can lead to heart attack and stroke. The research team has shown exposure to air pollution can increase the likelihood of the same risk factors that lead to heart disease, such as insulin resistance and type 2 diabetes.

 

In the mouse model study, three groups were observed: a control group receiving clean filtered air, a group exposed to polluted air for 24 weeks, and a group fed a high-fat diet. Interestingly, the researchers found that being exposed to air pollution was comparable to eating a high-fat diet. Both the air pollution and high-fat diet groups showed insulin resistance and abnormal metabolism – just like one would see in a pre-diabetic state.  

 

These changes were associated with changes in the epigenome, a layer of control that can masterfully turn on and turn off thousands of genes, representing a critical buffer in response to environmental factors. This study is the first-of-its-kind to compare genome-wide epigenetic changes in response to air pollution, compare and contrast these changes with that of eating an unhealthy diet, and examine the impact of air pollution cessation on these changes.

“The good news is that these effects were reversible, at least in our experiments” added Dr. Rajagopalan. “Once the air pollution was removed from the environment, the mice appeared healthier and the pre-diabetic state seemed to reverse.”

 

Dr. Rajagopalan explains that if you live in a densely polluted environment, taking actions such as wearing an N95 mask, using portable indoor air cleaners, utilizing air conditioning, closing car windows while commuting, and changing car air filters frequently could all be helpful in staying healthy and limiting air pollution exposure.

Next steps in this research involve meeting with a panel of experts, as well as the National Institutes of Health, to discuss conducting clinical trials that compare heart health and the level of air pollution in the environment. For example, if someone has a heart attack, should they be wearing an N95 mask or using a portable air filter at home during recovery? 

Dr. Rajagopalan and his team believe that it is important to address the environment as a population health risk factor and continue to diligently research these issues. The authors also note that these findings should encourage policymakers to enact measures aimed at reducing air pollution.

Credit: 
University Hospitals Cleveland Medical Center

Study finds signs of altruism in people's COVID-19 worries

Philadelphia, August 20, 2020 - When it comes to worrying about the COVID-19 pandemic, a new study demonstrates that people are more concerned about whether their family members could contract the virus or if they are unknowingly spreading the virus themselves than they are with contracting it. The study, conducted by researchers from the Lifespan Brain Institute (LiBI) of Children's Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania, also shows how increased resilience is able to reduce rates of anxiety and depression during the pandemic.

The findings were published online today by the journal Translational Psychiatry.

The COVID-19 pandemic has affected not only people's physical health, but also their mental health. Coping with these mental effects requires resilience, the ability to adapt in the face of adversity. Given the rapid spread of COVID-19 around the globe, the researchers at LiBI saw an opportunity to study resilience in the midst of a single global adversity.

In April, soon after stay-at-home measures were issued, the researchers launched an online survey at covid19resilience.org to study stress and resiliency during the COVID-19 pandemic. The survey measured six potential sources of stress during the pandemic: contracting the virus; dying from the virus; currently having the virus; having a family member contract the virus; unknowingly infecting others; and experiencing a significant financial burden.

The study involved 3,042 participants from the United States and Israel, ranging in age from 18 to 79. Most were living in locations with active stay-at-home orders at the time of the survey, and approximately 20% of those taking the survey were healthcare workers. Once they completed the questionnaire, participants' responses were measured for anxiety and depression. Of those who participated, distress about family members contracting the virus (48.5%) and unknowingly infecting others (36%) outweighed distress associated with contracting the virus themselves (19.9%). Rates of anxiety (22.2%) and depression (16.1%) were not significantly different between health care workers and non-health care workers.

"The opportunity to study mental resilience during this pandemic is unprecedented," said Ran Barzilay, MD, PhD, lead author, child and adolescent psychiatrist at CHOP, and Assistant Professor at LiBI. "Our frontline health care workers are acutely aware of the mental health challenges facing everyone right now, so there is an urgent need to quantify the effects of resilience and determine how future studies might guide us toward improving mental health under these changing circumstances."

Respondents with higher resilience scores had lower COVID-19-related worries, as well as a reduced rate of anxiety (65%) and depression (69%) across both health care workers and non-health care workers.

"Based on our study, it appears that people are more worried about others than themselves when reporting their COVID-19 related concerns, but encouragingly, resilience helps reduce these worries, as well as anxiety and depression," said Raquel Gur, MD, PhD, Professor of Psychiatry at the University of Pennsylvania and the director of LiBI. "As we get a better grasp of what constitutes resilience in people during COVID-19, we hope that soon we will be able to inform interventions that can enhance resilience, thereby mitigating the adverse effects of COVID-19 on mental health."

The survey website not only provided data to researchers, but also supplied unique information to participants, who immediately received personalized feedback upon completing the survey, including a resilience profile.

"We received many responses from participants telling us that they liked the interactive nature of the survey," said Dr. Barzilay. "Some of them explicitly said that they found the personalized feedback to be useful during these stressful times."

The researchers are continuing to gather information from the survey as the pandemic unfolds. The survey has already been translated to Spanish, French and Hebrew, and the researchers hope to collect data around the globe. So far more than 7,000 people have taken the survey, and the research team hopes to collect data over time that will shed light on the long-term effects of the COVID-19 high-stress environment.

Credit: 
Children's Hospital of Philadelphia

Discovery lays blame on supernova for extinction event nearly 360 million years ago

LAWRENCE, KANSAS -- Between a decline in biodiversity and a series of extinction events, the Late Devonian period was not the most hospitable time on Earth.

And then came one or more supernovae explosions whose resulting ionizing radiation was the final push that spelled the end for armored fish, most trilobites and other life.

In a paper published Aug. 18 in PNAS, three University of Kansas researchers and their colleagues lay out such a scenario for end-Devonian extinctions.

"For more than a decade, my colleagues and I have been interested in the possibility of ionizing radiation events causing extinction events on Earth," said Adrian Melott, professor emeritus of physics & astronomy at the University of Kansas.

Previous findings had pointed to this final extinction event of the Devonian happening in tandem with a drop in ozone in Earth's stratosphere.

"When I heard about the evidence for ozone depletion at the end-Devonian, it triggered thoughts about the possibility of a chain of nearby supernovae," Melott said.

Previous research had pointed to other possible causes for the ozone depletion, such as global warming, but not astrophysical sources like exploding stars.

However, a fellow KU researcher had findings that suggested otherwise. Brian Thomas, an adjunct researcher in physics & astronomy and professor of physics at Washburn University, had shown that atmospheric warming and the resulting injection of water into the lower stratosphere -- suggested as a mechanism to cause the ozone depletion -- were just not tenable.

Moreover, another KU researcher, Bruce Lieberman, had further findings that pointed to an astrophysical cause. Lieberman, a professor of ecology & evolutionary biology, had previously emphasized that the end-Devonian extinctions were part of a long period of diversity decline. This prolonged decline is then followed by evidence of pollen malformations, suggesting ionizing radiation as the cause.

That left a series of supernovae as the only tenable possibility, Melott said.

The researchers estimate the supernovae that triggered these events to be around 60 light years away. For context, Betelgeuse, a future supernova getting a lot of attention for its recent behavior, is about 600 light years away.

The supernovae that triggered end-Devonian extinction would have been close enough to cause some radiation damage on Earth, but not close enough for life-shattering damage.

"The cosmic rays from such a supernova will produce muons in the atmosphere, which are a very penetrating kind of radiation," Melott said. "They could cause internal damage in large animals and in organisms up to a half-mile down in the ocean."

The major ionization of the lower atmosphere may have led to a lot of lightning, he said, which could start fires and change the climate.

Credit: 
University of Kansas

Greenland ice sheet shows losses in 2019

image: Icebergs from Jakobshavn Isbræ, Ilulissat Icefjord, West Greenland.

Image: 
Ingo Sasgen

The Greenland Ice Sheet recorded a new record loss of mass in 2019. This was the finding of a team of international researchers after evaluating data from satellite observations and modelling data. The total loss amounted to 532 billion metric tons, more than in the previous record year 2012 (464 billion metric tons), which equates to an average global sea-level rise of 1.5 mm. After two years characterised by low loss of mass in 2017 and 2018, the ice sheet is now heading toward increasing mass losses. The five years with the greatest losses all occurred in the last decade. The ice loss in 2019 exceeded the increase due to snowfall by over 80%. The study was published today in the journal Communications Earth & Environment.

In order to determine the ice loss, researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI), the German Research Centre for Geosciences GFZ and international partners evaluated satellite data from the GRACE mission, and its successor mission, GRACE Follow-On (GRACE-FO). The satellites provided highly accurate measurements, which were used to create monthly maps of Earth's gravity. The redistribution of the masses, e.g. ice losses in the oceans, leads to temporal and spatial changes in Earth's gravitational forces. The researchers compared the satellite data with regional climate models that are specially designed to calculate the snowfall and the melting of the ice sheet.

"After a two-year 'breather', in 2019 the mass loss increased steeply and exceeded all annual losses since 1948, and probably for more than 100 years," says Ingo Sasgen, a glaciologist at the AWI in Bremerhaven and first author of the study. "There are increasingly frequent, stable high-pressure areas over the ice sheet, which promote the influx of warm air from the middle latitudes. We saw a similar pattern in the previous record year 2012."

The mass balance for a given a year is calculated using the difference between the ice increase due to snowfall and ice loss due to melting and ice discharge at the edge of the ice sheet. "The snowfall in 2019 was below the long-term average, and that also contributed to the record figure," explains Marco Tedesco, a professor at Columbia University and co-author of the study. "By comparing satellite data with regional climate models, we were able to see precisely which processes were involved and to what extent, and which general weather conditions were dominant," he adds.

The two satellite missions GRACE and GRACE-FO, which monitor the Earth's gravitational field, play a vital role in the continuous observations of the Greenland Ice Sheet. The measurements allow the mass changes in the ice sheet to be quantified. "The GRACE satellite mission, which ended in summer 2017, provided us with essential data on ice loss in the polar regions over a period of 15 years," explains Christoph Dahle from the GFZ, who is responsible for calculating the gravitational fields from the mission's raw data. "After a gap of about a year, in summer 2018 we were able to resume monitoring with the follow-on mission, GRACE-FO."

In summer, the Arctic warms roughly one and a half times as quickly as the global average. Added to this are the various feedback effects that increase the ice loss. "2017 and 2018 were very cold years in Greenland, with high snowfall," says Sasgen. The GRACE/GRACE-FO data shows, however, that in these years the mass balance was negative due to the high discharge from the glacier into the ocean. "We see substantial variations from year to year. But the five years with the highest losses since 1948 were all in the last decade," reports Sasgen.

Credit: 
GFZ GeoForschungsZentrum Potsdam, Helmholtz Centre

Researchers create nanoclusters that mimic biomolecules

ITHACA, N.Y. - Biological systems come in all shapes, sizes and structures. Some of these structures, such as those found in DNA, RNA and proteins, are formed through complex molecular interactions that are not easily duplicated by inorganic materials.

A research team led by Richard Robinson, associate professor of materials science and engineering, discovered a way to bind and stack nanoscale clusters of copper molecules that can self-assemble and mimic these complex biosystem structures at different length scales. The clusters provide a platform for developing new catalytic properties that extend beyond what traditional materials can offer.

Nanocluster core
Provided

The nanocluster core, shown here, connects to two copper caps fitted with special binding molecules, known as ligands, that are angled like propeller blades.

The team's paper, "Tertiary Hierarchical Complexity in Assemblies of Sulfur-Bridged Metal Chiral Clusters, " published July 27 in the Journal of the American Chemical Society.

"Just to be able to create inorganic clusters and precisely locate the atomic positions is a relatively new area because inorganic clusters don't easily assemble into organized crystals like organic molecules do. When we did get these to assemble, what we found was this strange, hierarchical organization that was completely unexpected," said Robinson, the paper's senior author. "This work could provide a fundamental understanding of how biosystems like proteins assemble themselves to create secondary structural organization, and it gives us an opportunity to start creating something that could imitate a natural living system."

The nanoclusters have three levels of organization with an interlocking, chiral design. Two copper caps are fitted with special binding molecules, known as ligands, that are angled like propeller blades, with one set tilting clockwise and the other counterclockwise (or left-handed and right-handed), all connecting to a core. The copper clusters are bridged with sulfur, and have a mixed oxidation state, which makes them more active in chemical reactions.

The clusters' flexible, adaptive nature makes them potential candidates for metabolic and enzymatic processes, as well as accelerating chemical reactions through catalysis. For example, they may be able to reduce carbon dioxide to alcohols and hydrocarbons.

"We'd like to develop catalytic materials with features that mimic natural enzymes," said co-author Jin Suntivich, associate professor of materials science and engineering. "Because our cluster has only 13 copper atoms, the tunability is more controllable than a nanoparticle with hundreds or thousands of atoms. With this higher level of control, we can think about building the clusters in a systematic manner. This can help reveal how each atom participates in reactions and how to rationally design a better one. We see it as a bridge to enzymes, where the atoms are assembled in a precise way to enable highly selective catalysis."

Radical Collaboration

While other inorganic clusters tend to swap electrons and change their properties when exposed to oxygen, the ligands stabilize the nanocluster over longer and longer lifecycles, making it reliably air stable. And because the ligands are strong conductors of electrons, the clusters may be useful in organic electronics, quantum computing and light-optical switches.

Robinson's group is now looking into replicating the same three-level hierarchy with other metals.

"Material scientists and chemical scientists have been trying to mimic these complex hierarchical structures in the lab, and we think we finally have something that nobody else has seen, and that we can build off of for future research," Robinson said.

Credit: 
Cornell University

Dilated blood vessels in the lung may explain low oxygen levels in severe cases of COVID-19

A new pilot study from the Icahn School of Medicine at Mount Sinai suggests that COVID-19 is causing significant dilation of the blood vessels of the lung, specifically the capillaries. This vasodilation is contributing to the very low oxygen levels seen in COVID-19 respiratory failure and also helps explain why the disease behaves differently than classic acute respiratory distress syndrome (ARDS). The study was published in the American Journal of Respiratory and Critical Care Medicine.

In classical ARDS, pulmonary inflammation leads to leaky pulmonary blood vessels that flood the lungs with fluid, making the lungs stiff and impairing oxygenation. Many patients with COVID-19 pneumonia demonstrate severe hypoxemia that is markedly out of proportion to the degree of lung stiffness. This disconnect between gas exchange and lung mechanics in COVID-19 pneumonia has raised the question of whether the mechanisms of hypoxemia in COVID-19 differ from those in classical ARDS.

The discovery was serendipitous. Researchers were initially assessing cerebral blood flow in mechanically ventilated COVID-19 patients with altered mental status to look for, among other things, abnormalities consistent with stroke. They used a robotic transcranial Doppler (TCD), the Lucid Robotic System by NovaSignal, to perform a "bubble study," which is a non-invasive and painless ultrasound technique.

"It is remarkable that a diagnostic machine used to study the brain could give us insight into the pathophysiology of a pulmonary disease. The benefit of using this particular system was that automated monitoring allowed providers to assess cerebral blood flow while minimizing the potential for exposure to COVID-19," said Alexandra Reynolds, MD, Assistant Professor of Neurosurgery, and Neurology, at the Icahn School of Medicine at Mount Sinai and Director of TeleNeurocritical Care for the Mount Sinai Health System.

During this study, agitated saline--saline with tiny microbubbles--is injected into the patient's vein and TCD is used to determine if those microbubbles appear in the blood vessels of the brain. Under normal circumstances, these microbubbles would travel to the right side of the heart, enter the blood vessels of the lungs, and ultimately get filtered by the pulmonary capillaries, because the diameter of the microbubbles is bigger than the diameter of the pulmonary capillaries. If the microbubbles are detected in the blood vessels of the brain, it implies that either there is a hole in the heart, so that blood can travel from the right to the left side of the heart without going through the lungs, or that the capillaries in the lungs are abnormally dilated, allowing the microbubbles to pass through.

In the pilot study, 18 mechanically ventilated patients with severe COVID-19 pneumonia underwent TCD with bubble study. Fifteen out of the 18 (83 percent) patients had detectable microbubbles, indicating the presence of abnormally dilated pulmonary blood vessels. The number of microbubbles detected by the TCD correlated with the severity of hypoxemia, indicating that the pulmonary vasodilations may explain the disproportionate hypoxemia seen in many patients with COVID-19 pneumonia. Previous studies have demonstrated that only 26 percent of patients with classical ARDS have microbubbles during a bubble study; furthermore, the number of these microbubbles does not correlate with the severity of hypoxemia, implying that pulmonary vascular dilations are not a major mechanism of hypoxemia in classical ARDS.

"It is becoming more evident that the virus wreaks havoc on the pulmonary vasculature in a variety of ways. This study helps explain the strange phenomenon seen in some COVID-19 patients known as 'happy hypoxia,' where oxygen levels are very low, but the patients do not appear to be in respiratory distress. If these findings are confirmed in larger studies, pulmonary microbubble transit may potentially serve as a marker of disease severity or even a surrogate endpoint in therapeutic trials for COVID-19 pneumonia. Future studies that investigate the use of pulmonary vascular constrictors in this patient population may be warranted," says senior author Hooman Poor, MD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai and Director of Pulmonary Vascular Disease at the Mount Sinai - National Jewish Health Respiratory Institute.

The pilot study has since expanded to collect data from approximately 80 patients, including those with less severe disease, and will evaluate the severity of microbubble transit and how it varies during the course of the disease.

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

New approach uses wild genes to improve biological nitrogen fixation in soybeans

image: Cover of the June issue of the MPMI journal

Image: 
Thi Nguyet Minh Dao and Svetlana Y. Folimonova.

One of the top four crops grown worldwide, soybean has been an integral part of Chinese agriculture for a long time, having been domesticated more than 6000 years ago. During the domestication process, certain traits are selected that make plants easier to cultivate and cook and other traits can be lost. Wild ancestors of domesticated crops can be important reservoirs of agronomic traits that have been lost. This is especially important when it comes to disease resistance.

A group of scientists in China began a study of wild soybeans to find genetic regions involved with interacting with beneficial microbes that have been lost in domesticated soybeans. This group cultivated soybean lines that included small regions of DNA from their wild ancestors and found that some lines responded differently to different strains of the beneficial bacteria known as Sinorhizobium fredii.

These different responses, the scientists found, were related to whether or not the bacterial strains had fully functional type 3 secretion systems (T3SS), which are used by bacteria to inject protein effectors into plant cells. They followed a dirigent protein named DRR1 and found that it interacted genetically with the bacterial T3SS system to alter the number of nodules a root system forms.

This new genetic approach will help scientists access some of the genetic diversity of soybean ancestors to improve biological nitrogen fixation, an important part of sustainable agriculture, in modern soybean cultivars. For more information, read "RNA Sequencing-Associated Study Identifies GmDRR1 as Positively Regulating the Establishment of Symbiosis in Soybean," published May 28, 2020 in the MPMI journal.

Credit: 
American Phytopathological Society

Firefighters exposed to more potentially harmful chemicals than previously thought

image: Firefighters in the Kansas City, Missouri, area, wore personal passive samplers in the shape of a military-style dog tag made of silicone on an elastic necklace. The samplers detect chemicals in the air.

Image: 
Carolyn Poutasse, Oregon State University.

CORVALLIS, Ore. - A new Oregon State University study suggests that firefighters are more likely to be exposed to potentially harmful chemicals while on duty compared to off duty.

The on-duty firefighters in the Kansas City, Missouri, area experienced higher exposures of polycyclic aromatic hydrocarbons, or PAHs, which are a family of chemicals that are known to have the potential to cause cancer. They were also exposed to 18 PAHs that have not been previously reported as firefighting exposures in earlier research.

The study, funded by the Federal Emergency Management Agency, is published in the journal Environment International.

The results are important because previous studies have shown that firefighters have an increased risk of developing cancer and other damaging health effects, said study lead Kim Anderson, an environmental chemist and Extension specialist in OSU's College of Agricultural Sciences.

PAHs are a large group of chemical compounds that contain carbon and other elements. They form naturally after almost any type of combustion, both natural and human-created. In addition to burning wood, plants and tobacco, PAHs are also in fossil fuels.

"We don't have enough data to profile the source of the PAHs, but we know PAHs appear from combustion, and obviously combustion is their work," Anderson said. "They are also putting on a heavy load of protective gear that has PAHs, and they use cleaning products that have PAHs."

The firefighters in the study wore personal passive samplers in the shape of a military-style dog tag made of silicone on an elastic necklace. The tags are made of the same material as OSU's patented silicone wristbands that Anderson's lab has been using for several years to study chemical exposure in humans and cats.

This study demonstrates that the dog tags, which absorb chemicals from the air and skin, appear to be a reliable sampling technology necessary for assessing chemical exposures in firefighters, Anderson said.

"I'm quite confident those exposures existed but if you don't have something to help you find them you don't know for sure," Anderson said. "Certainly, we found that it's a lot more than what people had thought."

For their study, the researchers sampled individual firefighters' exposures at two departments - the Raytown Fire Protection District and Southern Platte Fire Protection District. They defined the Raytown department as a "high call volume" department, with a historic average of 12 fire calls per month, and the Southern Platte department as "low call volume," with less than two calls per month historically.

After completing a survey on demographics, occupational history, and suspected current exposures, the recruited firefighters wore a dog tag during the next 30 on- and off-shift days. During fire calls, tags were worn over clothing but underneath their gear. The firefighters were instructed to wear the dog tags continuously during all regular activities, including eating, showering and sleeping. Sampling occurred from November 2018 to April 2019.

When they analyzed the dog tags that were returned to Anderson's lab at Oregon State, 45 unique PAHs, of which 18 have not been previously reported as firefighting exposures, were detected. PAH exposures increased as the number of fires a participant responded to increased. PAH concentrations were not only higher when on-duty compared to off-duty, but also higher from the high call volume department compared to the low call volume department.

Each of the participating firefighters has been provided a report on their basic health information and chemical exposure, Anderson said. The participants also received a fact sheet about firefighters and cancer risk. The fact sheet includes some simple steps firefighters can take to reduce their exposure to harmful chemicals, such as always wearing their personal protective equipment, taking a shower after each fire and before ending their shift, and cleaning their gear after every fire.

Credit: 
Oregon State University

First daily surveillance of emerging COVID-19 hotspots

image: Weekly clusters resulting from the prospective space-time scan statistic.

Image: 
Hohl et al., Spatial and Spatio-temporal Epidemiology (2020)

Over the course of the coronavirus epidemic, COVID-19 outbreaks have hit communities across the United States. As clusters of infection shift over time, local officials are forced into a whack-a-mole approach to allocating resources and enacting public health policies. In a new study led by the University of Utah, geographers published the first effort to conduct daily surveillance of emerging COVID-19 hotspots for every county in the contiguous U.S. The researchers hope that timely, localized data will help inform future decisions.

Using innovative space-time statistics, the researchers detected geographic areas where the population had an elevated risk of contracting the virus. They ran the analysis every day using daily COVID-19 case counts from Jan. 22 to June 5, 2020 to establish regional clusters, defined as a collection of disease cases closely grouped in time and space. For the first month, the clusters were very large, especially in the Midwest. Starting on April 25, the clusters become smaller and more numerous, a trend that persists until the end of the study.

The article published online on June 27, 2020, in the journal Spatial and Spatio-temporal Epidemiology. The study builds on the team’s previous work by evaluating the characteristics of each cluster and how the characteristics change as the pandemic unfolds.

“We applied a clustering method that identifies areas of concern, and also tracks characteristics of the clusters—are they growing or shrinking, what is the population density like, is relative risk increasing or not?” said Alexander Hohl, lead author and assistant professor at the Department of Geography at the U. “We hope this can offer insights into the best strategies for controlling the spread of COVID-19, and to potentially predict future hotspots.”

The research team, including Michael Desjardins of Johns Hopkins Bloomberg School of Public Health’s Spatial Science for Public Health Center and Eric Delmelle and Yu Lan of the University of North Carolina at Charlotte, have created a web application of the clusters that the public can check daily at COVID19scan.net. The app is just a start, Hohl warned. State officials would need to do smaller scale analysis to identify specific locations for intervention.

“The app is meant to show where officials should prioritize efforts—it’s not telling you where you will or will not contract the virus,” Hohl said. “I see this more as an inspiration, rather than a concrete tool, to guide authorities to prevent or respond to outbreaks. It also gives the public a way to see what we’re doing.”

The researchers used daily case counts reported in the COVID-19 Data Repository from the Center for Systems Science and Engineering at Johns Hopkins University, which lists cases at the county level in the contiguous U.S. They used the U.S. Census website’s 2018 five-year population estimates within each county.

To establish the clusters, they ran a space-time scan statistic that takes into account the observed number of cases and the underlying population within a given geographic area and timespan. Using SatScan, a widely used software, they identified areas of significantly elevated risk of COVID-19. Due to the large variation between counties, evaluating risk is tricky. Rural areas and small, single counties may not have large populations, therefore just a handful of cases would make risk go up significantly.

This study is the third of the research group’s iteration using the statistical method for detecting and monitoring COVID-19 clusters in the U.S. Back in May, the group published their first geographical study to use the tracking method, which was also of the first paper published by geographers analyzing COVID-19. In June, they published an update.

“May seems like an eternity ago because the pandemic is changing so rapidly,” Hohl said. “We continue to get feedback from the research community and are always trying to make the method better. This is just one method to zero in on communities that are at risk.”

A big limitation of the analysis is the data itself. COVID-19 reporting is different for each state. There’s no uniform way that information flows from the labs that confirm the diagnoses, to the state health agencies to the COVID-19 Data Repository from the Center for Systems Science and Engineering at Johns Hopkins University, where the study gets its data. Also, the testing efforts are quite different between states, and the team is working to adjust the number of observed cases to reflect a state’s efforts. Hohl is also working with other U researchers to look at the relationship between social media and COVID-19 to predict the future trajectory of outbreaks.

“We’ve been working on this since COVID-19 first started and the field is moving incredibly fast,” said Hohl. “It’s so important to get the word out and react to what else is being published so we can take the next step in the project.”

Credit: 
University of Utah

Your in-laws' history of drinking problems could lead to alcohol issues of your own

The statistics are sobering. More than 14 million American adults suffer from some form of alcohol use disorder (AUD), a chronic inability to stop or control alcohol use despite the negative consequences. This is according to the National Institute on Alcohol Abuse and Alcoholism, a part of the National Institutes of Health.

The causes of AUD are complex and can include a mix of genetic, environmental, and social factors, including a family history of alcoholism. This familial effect, however, may be more complicated than first assumed.

New research published in the journal Psychological Science has uncovered a previously unrecognized family connection to AUD: the drinking habits of a person's in-laws. This study suggests that marriage to a spouse who as a child was exposed to parental alcohol misuse increases that person's likelihood of developing AUD, even if the spouse does not have a drinking disorder.

"Our goal here was to examine whether a spouse's genetic makeup influences risk for AUD," said Jessica Salvatore, an assistant professor of psychology at Virginia Commonwealth University, and lead author on the paper. "In a somewhat surprising twist, we found that it wasn't the spouse's genetic makeup that influenced AUD risk. Rather, it was whether the spouse was raised by an AUD-affected parent."

The researchers analyzed marital information on more than 300,000 couples in Swedish national population registries, finding that marriage to a spouse with a predisposition toward alcohol use disorder increased risk for developing AUD. This increased risk was not explained by socioeconomic status, the spouse's AUD status, nor contact with the spouse's parents. Instead, the researchers found that, rather than genetics, this increased risk reflected the psychological consequences of the spouse having grown up with an AUD-affected parent.

"Growing up with an AUD-affected parent might teach people to act in ways that reinforce a spouse's drinking problem," said Salvatore. "For example, taking care of a spouse when they have a hangover."

The study's findings underscore the pernicious and long-lasting impact of growing up with a parent with AUD, extending even to the spouses of their adult children.

"It demonstrates the long reach that parental alcohol problems have on the next generation," Salvatore said. "It's not just the offspring of affected parents who are at risk, it's the people those offspring end up marrying, too."

The findings are consistent with evidence from other research labs, she said, which suggests that those who grow up with a parent with an alcohol use disorder may be at particularly high risk of using alcohol as a "tool" to improve their marital interactions.

"These kinds of processes may inadvertently lead a spouse down the path of alcohol misuse," she said. "To be clear, my guess is that these processes are out of people's conscious control. No one wants to 'give' their spouse an alcohol problem."

The study's findings are an important contribution to a burgeoning area of research on social genetic effects, or the effects of a social partner's genetic makeup, Salvatore said. Conclusions from previous studies of social genetic effects were limited by the fact that people's genotypes were correlated with their rearing environments. In other words, in prior studies it was difficult to say whether effects were attributable to the partner's genes versus how they were raised because their parents provided both their genes and their home lives.

"What we were able to do in our study was tease apart the effects of the social partner (spouse's) genes and the rearing environment," she said. "And when we did that, what we found surprised us: It's something about the spouse being raised by a parent with a drinking problem, rather than the spouse's genetic makeup, that influences a person's risk for developing an alcohol problem."

The study's findings could prove valuable when it comes to treating couples struggling with alcohol. The findings reinforce the idea that interventions for substance-use disorders should be administered at the level of a couple or the family (for those who have a partner) rather than at the individual level, Salvatore said.

This study is part of Salvatore's larger body of research that seeks to understand "how the people we love shape the way we drink."

"In the best-case scenario, spouses can be one of our first defenses against poor health--they bug us to schedule our annual exams, and they're among the first to notice if we're feeling blue or tipping too many drinks back. But spouses can also be a liability for poor health," she said. "The results from this study underscore how a spouse's experiences in his/her family of origin can be a risk factor for the development of alcohol problems."

Credit: 
Association for Psychological Science

Genetics: Romantic relationship dynamics may be in our genes

Variations in a gene called CD38, which is involved in attachment behaviour in non-human animals, may be associated with human romantic relationship dynamics in daily life, according to a study published in Scientific Reports.

Jennifer Bartz, Gentina Sadikaj, and colleagues examined data on 111 heterosexual couples (222 individuals) who reported their social behaviour - which included smiling and laughing with others, making sarcastic comments, asking others to do something or giving in - their perception of their partner's behavior, and their feelings during their interactions with one another over a 20-day period. Out of the 222 individuals 118 (65 women and 53 men) also provided genetic information.

The authors found that a variation of the CD38 gene - CD38.rs3796863 - was associated with an individual's communal behavior, such as the expression of affection, in daily interactions with their romantic partner. CD38.rs3796863 has two variants (alleles): A and C. The gene can therefore be present as three combinations, or genotypes: AA, CC and AC. The authors found that individuals with the CC genotype reported higher communal behavior than individuals with AA or AC genotypes. Those with the CC genotype were also more likely to see their partner as behaving communally and they experienced fewer negative feelings, such as worry, frustration or anger than AA or AC genotypes. Those with the CC genotype also reported higher levels of relationship adjustment, including perceptions of relationship quality and support.

The authors also observed a pattern in couples: participants' own behavior, their perception of their partner's behavior and their experience of negative feelings and relationship adjustment were equally related to their partner's genotype as to their own genotype.

The findings suggest that variations in CD38 may play a key role in behaviours and perceptions that support bonding in humans.

Credit: 
Scientific Reports

3D printing 'greener' buildings using local soil

image: Scientists have developed a method to 3D print structures using local soil.

Image: 
Aayushi Bajpayee

WASHINGTON, Aug. 20, 2020 -- The construction industry is currently facing two major challenges: the demand for sustainable infrastructure and the need to repair deteriorating buildings, bridges and roads. While concrete is the material of choice for many construction projects, it has a large carbon footprint, resulting in high waste and energy expenditure. Today, researchers report progress toward a sustainable building material made from local soil, using a 3D printer to create a load-bearing structure.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo. ACS is holding the meeting through Thursday. It features more than 6,000 presentations on a wide range of science topics.

"The environmental impact of the construction industry is an issue of growing concern," says Sarbajit Banerjee, Ph.D., the project's principal investigator. "Some researchers have turned to additive manufacturing, or building structures layer by layer, which is often done with a 3D printer. That advance has begun to transform this sector in terms of reducing waste, but the materials used in the process need to be sustainable as well."

For example, construction projects using extruded layers of concrete have highlighted the potential of additive manufacturing for building structures quickly and cheaply. However, concrete manufacturing is responsible for approximately 7% of carbon dioxide emissions according to the International Energy Agency, and cannot be recycled.

"Historically, humans used to build with locally sourced materials, such as adobe, but the move to concrete has raised many environmental issues," says Aayushi Bajpayee, a graduate student in Banerjee's lab at Texas A&M University. She is presenting the work at the meeting. "Our thought was to turn the clock back and find a way to adapt materials from our own backyards as a potential replacement for concrete."

An advantage to using local soil in construction is that the materials would not need to be manufactured and transported to the building site, reducing both costs and environmental damage. Banerjee and Bajpayee also say that additive manufacturing with soil could one day be used beyond Earth, to create settlements on the moon or even Mars.

Soil is typically classified by the layers of materials it comprises, beginning with the top organic layer where plants grow and ending at the hard bedrock of the earth's crust. Beneath the initial organic layer is clay, which gives soil its plastic, moldable character that the researchers capitalized on in their project.

The researchers began by collecting soil samples from a colleague's backyard and tailoring the material with a new environmentally friendly additive so that it would bind together and be easily extruded through the 3D printer. Because soils vary greatly by location, their aim was to have a chemistry "toolkit" that could transform any type of soil into printable building material. From there Bajpayee built small-scale test structures, cubes measuring two inches on each side, to see how the material performed when extruded into stacked layers.

The next step was to ensure that the mixture is load bearing, meaning that it will stand up to the weight of the layers but also other materials used in construction such as rebar and insulation. To help with this, the researchers strengthened the clay mixture by "zippering" the microscopic layers on its surface to prevent it from absorbing water and expanding, which would compromise the printed structure. With this method, the researchers showed that the material could hold twice as much weight as the unmodified clay mixture.

Next, the team plans to improve the soil's load-bearing capabilities in order to scale up their test structures and get as close to a replacement for concrete as possible. In addition, they are gathering data to see whether these 3D printed structures are as environmentally friendly as they envision, especially in terms of carbon footprint and recycling potential. Once they have a better picture of the chemistry, functionality and feasibility of building with local soils, they plan to further explore how this technology can be used beyond our own planet.

Credit: 
American Chemical Society

Massive, well-preserved reptile found in the belly of a prehistoric marine carnivore

image: This image shows the ichthyosaur specimen with its stomach contents visible as a block that extrudes from its body.

Image: 
Ryosuke Motani

When paleontologists digging in a quarry in southwestern China uncovered the nearly complete skeleton of a giant, dolphin-like marine reptile known as an ichthyosaur, they didn't expect to find another fossil in its stomach. This second skeleton belonged to a four-meter-long, lizard-like aquatic reptile known as a thalattosaur and is one of the longest fossils ever found in the stomach of a prehistoric marine reptile. While the researchers can't say for sure whether the thalattosaur was scavenged or preyed upon, their work could be the oldest direct evidence that Triassic marine reptiles like ichthyosaurs--previously thought to be cephalopod feeders--were apex megapredators. The findings appear August 20th in the journal iScience.

"If you look across all the similar marine reptiles that lived in the age of dinosaurs, we've actually never found something articulated like this in the stomach," says co-author Ryosuke Motani, a professor of paleobiology at the University of California, Davis. "Our ichthyosaur's stomach contents weren't etched by stomach acid, so it must have died quite soon after ingesting this food item. At first, we just didn't believe it, but after spending several years visiting the dig site and looking at the same specimens, we finally were able to swallow what we were seeing."

Because stomach contents are rarely found in marine fossils, researchers rely on tooth and jaw shapes to learn what prehistoric species may have eaten. While prehistoric apex predators are typically thought to have large teeth with sharp cutting edges, some modern predatory species like crocodiles use blunt teeth to consume large prey items with grasping force instead of cutting. Ichthyosaurs share these blunter teeth, but with no direct evidence of large prey consumption in these prehistoric marine reptiles, scientists believed that they fed on small prey like cephalopods.

However, the discovery of the giant thalattosaur in the stomach of the ichthyosaur found by Motani, Da-Yong Jiang, a paleontologist at Peking University in China, and their team suggests that this was not the case. "Now, we can seriously consider that they were eating big animals, even when they had grasping teeth," says Motani. "It's been suggested before that maybe a cutting edge was not crucial, and our discovery really supports that. It's pretty clear that this animal could process this large food item using blunt teeth."

While the researchers now know that the ichthyosaur could eat animals as large as the thalattosaur, they don't know if it killed this individual, or simply scavenged it. "Nobody was there filming it," says Motani. However, there is reason to believe this was not a case of scavenging: modern marine decomposition studies suggest that if left to decay, the thalattosaur's limbs would disintegrate and detach before the tail. Instead, the researchers found the opposite in these fossils. The thalattosaur's limbs were at least partially attached to its body in the stomach, while a disconnected tail was found many yards away, leading the researchers to believe it was ripped off and left behind by a predator like the ichthyosaur.

Whether or not the ichthyosaur killed its last meal, the fossil provides the oldest direct evidence that these giant marine reptiles consumed animals larger than humans. "We now have a really solid articulated fossil in the stomach of a marine reptile for the first time," Motani says. "Before, we guessed that they must have eaten these big things, but now, we can say for sure that they did eat large animals. This also suggests that megapredation was probably more common than we previously thought."

The team is still excavating the site where the pair of fossils were found, which has now been turned into a museum. "We've been digging in that particular quarry for more than ten years now, and still, new things are coming out," says Motani. "At this point, it's beyond our initial expectations, and we'll just have to see what we'll discover next."

Credit: 
Cell Press

Ichthyosaur's last meal is evidence of triassic megapredation

image: The stomach of this 240-million year old fossil ichthyosaur contains the mid-section of another marine reptile that in life would have been only slight smaller. It's the first direct evidence of ancient megapredation -- one large animal eating another.

Image: 
Da-Yong Jiang, et al, iScience

Some 240 million years ago, a dolphin-like ichthyosaur ripped to pieces and swallowed another marine reptile only a little smaller than itself. Then it almost immediately died and was fossilized, preserving the first evidence of megapredation, or a large animal preying on another large animal. The fossil, discovered in 2010 in southwestern China, is described in a paper published Aug. 20 in the journal iScience.

The ichthyosaurs were a group of marine reptiles that appeared in the oceans after the Permian mass extinction, about 250 million years ago. They had fish-like bodies similar to modern tuna, but breathed air like dolphins and whales. Like modern orca or great white sharks, they may have been apex predators of their ecosystems, but until recently there has been little direct evidence of this.

When a specimen of the ichthyosaur Guizhouichthyosaurus was discovered in Guizhou province, China in 2010, researchers noticed a large bulge of other bones within the animal's abdomen. On examination, they identified the smaller bones as belonging to another marine reptile, Xinpusaurus xingyiensis, which belonged to a group called thalattosaurs. Xinpusaurus was more lizard-like in appearance than an ichthyosaur, with four paddling limbs.

"We have never found articulated remains of a large reptile in the stomach of gigantic predators from the age of dinosaurs, such as marine reptiles and dinosaurs," said Ryosuke Motani, professor of earth and planetary sciences at the University of California, Davis, and coauthor on the paper. "We always guessed from tooth shape and jaw design that these predators must have fed on large prey but now we have direct evidence that they did."

The Guizhouichthyosaurus was almost five meters (15 feet) long, while the researchers calculate its prey was about four meters (12 feet) long, although thalattosaurs had skinnier bodies than ichythyosaurs. The predator's last meal appears to be the middle section of the thalattosaur, from its front to back limbs. Interestingly, a fossil of what appears to be the tail section of the animal was found nearby.

Predators that feed on large animals are often assumed to have large teeth adapted for slicing up prey. Guizhouichthyosaurus had relatively small, peg-like teeth, which were thought to be adapted for grasping soft prey such as the squid-like animals abundant in the oceans at the time. However, it's clear that you don't need slicing teeth to be a megapredator, Motani said. Guizhouichthyosaurus probably used its teeth to grip the prey, perhaps breaking the spine with the force of its bite, then ripped or tore the prey apart. Modern apex predators such as orca, leopard seals and crocodiles use a similar strategy.

Credit: 
University of California - Davis