Culture

Irvine, Calif., - Physical evidence found in caves in Laos helps tell a story about a connection between the end of the Green Sahara - when once heavily vegetated Northern Africa became a hyper-arid landscape - and a previously unknown megadrought that crippled Southeast Asia 4,000 to 5,000 years ago.

In a paper published today in Nature Communications, scientists at the University of California, Irvine, the University of Pennsylvania, William Paterson University of New Jersey and other international institutions explain how this major climate transformation led to a shift in human settlement patterns in Southeast Asia, which is now inhabited by more than 600 million people.

"In this study, we provide the first proof for a strong link between the end of the Green Sahara and Southeast Asian monsoon failure during the mid- to late Holocene period," said co-author Kathleen Johnson, UCI associate professor of Earth system science. "Our high-resolution and well-dated record suggests a strong connection between Northern Africa and mainland Southeast Asia during this time."

To create a paleoclimate record for the study, Johnson and other researchers gathered stalagmite samples from caves in Northern Laos. In her UCI laboratory, they measured the geochemical properties of the oxygen and carbon isotopes, carbon-14, and trace metals found in the specimens. This helped them verify the occurrence of the drought and extrapolate its impacts on the region.

Johnson said they combined data from the analysis of these stalagmite-derived proxies with a series of idealized climate model simulations - conducted by co-author Francesco Pausata of the University of Quebec in Montreal - in which Saharan vegetation and dust concentrations were altered in a way that permitted them to investigate the ocean-atmosphere feedbacks and teleconnections associated with such an abrupt shift in precipitation.

The modeling experiments suggested that reduced plant growth in the Sahara led to increased airborne dust that acted to cool the Indian Ocean and shift the Walker circulation pattern eastward, causing it to behave in ways similar to modern-day El Niño events. This, ultimately, led to a large reduction in monsoon moisture across Southeast Asia that lasted more than 1,000 years, according to Johnson.

Anthropologists and archaeologists have previously studied the effects of the demise of the Green Sahara, also known as the African humid period, on population centers closer to Western Asia and North Africa, noting the collapse of the Akkadian Empire of Mesopotamia, the de-urbanization of the Indus Civilization (near present-day Pakistan and India) and the spread of pastoralism along the Nile River.

But the link to the origin of the Southeast Asia megadrought and lifestyle pattern shifts in the region had not been previously investigated, according to lead author Michael Griffiths, professor of environmental science at William Paterson University of New Jersey.

"Archaeologists and anthropologists have been studying this event for decades now, in terms of societal adaptations and upheavals, but its exact cause has eluded the scientific community," said Griffiths, who was a National Oceanic and Atmospheric Administration-supported postdoctoral scholar in Johnson's lab and has collaborated with her on this research topic for more than 10 years.

"Results from this work provide a novel and convincing explanation for the origin of the Southeast Asia megadrought and could help us better understand, to varying degrees, the observed societal shifts across many parts of the tropics and extra-tropics," he said.

The researchers suggest that the centuries-long megadrought corresponds to the "missing millennia" in Southeast Asia between 4,000 and 6,000 years ago, a time characterized by a noticeable lack of archaeological evidence in interior Southeast Asia compared to earlier and later portions of the Holocene.

They propose that the mid-Holocene megadrought may have been an impetus for mass population movements and the adoption of new, more resilient subsistence strategies - and that it should now be considered as a possible driver for the inception of Neolithic farming in mainland Southeast Asia.

"This is outstanding evidence for the type of climate change that must have affected society, what plants were available, what animals were available," said co-author Joyce White, adjunct professor of anthropology at the University of Pennsylvania. "All of life had to adjust to this very different climate. From an archaeological point of view, this really is a game changer in how we try to understand or reconstruct the middle Holocene period."

Physical evidence found in caves in Laos helps tell a story about a connection between the end of the Green Sahara, when once heavily vegetated Northern Africa became a hyper-arid landscape, and a previously unknown megadrought that crippled Southeast Asia 4,000 to 5,000 years ago.

In a paper published in Nature Communications, scientists at the University of California, Irvine, University of Pennsylvania, William Paterson University of New Jersey, and other international institutions explain how this major climate transformation led to a shift in human settlement patterns in Southeast Asia, which is now inhabited by more than 600 million people.

"In this study, we provide the first proof for a strong link between the end of the Green Sahara and Southeast Asian monsoon failure during the mid- to late Holocene period," said co-author Kathleen Johnson, UCI associate professor of Earth system science. "Our high-resolution and well-dated record suggests a strong connection between Northern Africa and mainland Southeast Asia during this time."

To create a paleoclimate record for the study, Johnson and other researchers gathered stalagmite samples from caves in Northern Laos. In her UCI laboratory, they measured the geochemical properties of the oxygen and carbon isotopes, carbon-14, and trace metals found in the specimens. This helped them verify the occurrence of the drought and extrapolate its impacts on the region.

Johnson said they combined data from the analysis of these stalagmite-derived proxies with a series of idealized climate model simulations--conducted by co-author Francesco Pausata of the University of Quebec in Montreal--in which Saharan vegetation and dust concentrations were altered in a way that permitted them to investigate the ocean-atmosphere feedbacks and teleconnections associated with such an abrupt shift in precipitation.

The modeling experiments suggested that reduced plant growth in the Sahara led to increased airborne dust that acted to cool the Indian Ocean and shift the Walker circulation pattern eastward, causing it to behave in ways similar to modern-day El Niño events. This, ultimately, led to a large reduction in monsoon moisture across Southeast Asia that lasted more than 1,000 years, according to Johnson.

Anthropologists and archaeologists have previously studied the effects of the demise of the Green Sahara, also known as the African humid period, on population centers closer to Western Asia and North Africa, noting the collapse of the Akkadian Empire of Mesopotamia, the de-urbanization of the Indus Civilization (near present-day Pakistan and India) and the spread of pastoralism along the Nile River.

But the link to the origin of the Southeast Asia megadrought and lifestyle pattern shifts in the region had not been previously investigated, according to lead author Michael Griffiths, professor of environmental science at William Paterson University of New Jersey.

"Archaeologists and anthropologists have been studying this event for decades now, in terms of societal adaptations and upheavals, but its exact cause has eluded the scientific community," said Griffiths, who was a National Oceanic and Atmospheric Administration-supported postdoctoral scholar in Johnson's lab and has collaborated with her on this research topic for more than 10 years.

"Results from this work provide a novel and convincing explanation for the origin of the Southeast Asia megadrought and could help us better understand, to varying degrees, the observed societal shifts across many parts of the tropics and extra-tropics," he said.

The researchers suggest that the centuries-long megadrought corresponds to the "missing millennia" in Southeast Asia between 4,000 and 6,000 years ago, a time characterized by a noticeable lack of archaeological evidence in interior Southeast Asia compared to earlier and later portions of the Holocene.

They propose that the mid-Holocene megadrought may have been an impetus for mass population movements and the adoption of new, more resilient subsistence strategies, and that it should now be considered as a possible driver for the inception of Neolithic farming in mainland Southeast Asia.

"This is outstanding evidence for the type of climate change that must have affected society, what plants were available, what animals were available," said co-author Joyce White, adjunct professor of anthropology at the University of Pennsylvania. "All of life had to adjust to this very different climate. From an archaeological point of view, this really is a game changer in how we try to understand or reconstruct the middle Holocene period."

A team of scientists at the Nagoya University Institute of Transformative Bio-Molecules (WPI-ITbM) have developed a method for visualizing microtubule dynamics and cell membrane protein endocytosis in living plant cells, an important step forward in plant cell biology.

SNAP-tag visualization of in vivo protein dynamics, a method which binds dyes to proteins to allow fluorescent imaging, has made a wide range of contributions to medical and biological study, for example in cancer research. However, live cell imaging using SNAP-tag with synthetic dyes in plant science has been impossible, as synthetic dyes are unable to reach the target proteins due to the presence of the cell wall in plant cells.

In this study, the research team demonstrated that it was possible to perform live cell imaging using SNAP-tag even in plants, using three types of synthetic dyes which bond to the SNAP-tag to mark microtubules, part of the cytoskeleton. They were able to use a particular dye that does not permeate the cell membrane and fluoresces only when it bonds with SNAP-tag to exclusively mark the auxin transporters in the cell membrane, visualizing the process of membrane proteins being taken into the cell (endocytosis) after they had been marked. Thus, they were able to clearly differentiate between transporter proteins which had been newly synthesized inside the cell and those taken into the cell by endocytosis.
They then used tobacco cells to find out which of 31 different dyes were able to enter the cell. Interestingly, it was found that 23 out of these 31 were taken into the tobacco cells, that the majority of them could be used with SNAP-tag to mark cytosolic components in plant cells, and that those which could not permeate the cell membrane could be used to mark membrane proteins outside the cell.

This study provides a new technique for the fluorescent marking of proteins in plant cells, and represent an important step forward in plant cell biology research. It is expected to find use in superresolution imaging using extremely light stable markers, and techniques for determining place- and time-specific pH and Ca2+ levels.

Women are underrepresented in the field of academic surgery, but women surgeons are earning a disproportionate share of research grants from the National Institutes of Health, a new study has found.

Women make up 19% of surgery faculty at academic health systems but held 26.4% of prestigious "R01" grants in place at surgery departments as of October 2018, the researchers found.

"Female surgeon-scientists are underrepresented within academic surgery, but hold a greater than anticipated proportion of NIH funding," said researcher Shayna L. Showalter, MD, a breast surgical oncologist at UVA Health and the UVA Cancer Center. "This means that female surgeon-scientists are a crucial component of future surgical research."

Women in Surgery

Showalter and colleagues queried the number of grants from surgery departments throughout the country to determine the percentage of R01 grants held by women. They identified 212 grants held by 159 principal investigators. Of those 159 investigators, 42 were women, holding a total of 49 R01 grants. "Female surgeon scientists are doing impressive work and have been able to succeed in a very competitive research environment," Showalter said.

Diving deeper, the researchers determined that women were more likely than men to be first-time grant recipients. More than 73% of women were first-time recipients, compared with 54.8% of men. "Within the research community, we are potentially moving away from the tradition of awarding funding to longstanding, proven researchers," Showalter said. "Females in this study were twice as likely to be first-time grant recipients. I hope that the focus continues to be on awarding funding to a diverse group of surgeon-scientists."

Women who held R01 grants were more likely to be part of a department with a female chair or that is more than 30 percent female, the researchers determined. They also found that women had fewer research articles published in scientific journals than did their male colleagues. "This finding may be related to the number of first-time grants and is consistent with previous studies that have demonstrated that women in academic surgery have fewer publication in general than men,' Showalter said.

The researchers encouraged surgery departments to nurture and promote female faculty, and to advocate for women in leadership positions. Strong mentorship programs are important, Showalter said.

"Currently, there are a number of accomplished female surgeon-scientists, and I am confident that many more will play crucial roles in the future of surgical research," she said. "As a community within academia, we need to support and promote a diverse faculty."

Solar flares emit sudden, strong bursts of electromagnetic radiation from the Sun's surface and its atmosphere, and eject plasma and energetic particles into inter-planetary space. Since large solar flares can cause severe space weather disturbances affecting Earth, to mitigate their impact their occurrence needs to be predicted. However, as the onset mechanism of solar flares is unclear, most flare prediction methods so far have relied on empirical methods.

The research team led by Professor Kanya Kusano (Director of the Institute for Space-Earth Environmental Research, Nagoya University) recently succeeded in developing the first physics-based model that can accurately predict imminent large solar flares. The work was published in the journal Science on July 31, 2020.

The new method of flare prediction, called the kappa scheme, is based on the theory of "double-arc instability," that is a magnetohydrodynamic (MHD) instability triggered by magnetic reconnection. The researchers assumed that a small-scale reconnection of magnetic field lines can form a double-arc (m-shape) magnetic field and trigger the onset of a solar flare. The kappa -scheme can predict how a small magnetic reconnection triggers a large flare and how a large solar flare can occur.

The predictive model was tested on about 200 active regions during solar cycle 24 from 2008 to 2019 using data obtained by NASA's Solar Dynamics Observatory (SDO) satellite. It was demonstrated that with few exceptions, the kappa-scheme predicts most imminent solar flares, as well as the precise location they will emerge from. The researchers also discovered that a new parameter - the "magnetic twist flux density" close to a magnetic polarity inversion line on the solar surface - determines when and where solar flares probably occur and how large they are likely to be.

Previous flare prediction methods have relied on empirical relations in which the predictions of the previous day tend to continue into the next day even if flare activity changes. In contrast, the kappa-scheme predicts large solar flares through a physics-based approach regardless of previous flare activity. While it takes a lot more work to implement the scheme in real-time operational forecasting, this study shows that the physics-based approach may open a new direction for flare prediction research.

Editor's Note: The paper, Asymmetric remote C–H borylation of aliphatic amides and esters with a modular iridium catalyst, was published in the journal Science, and will be withdrawn at 14.00 EDT on 28 April 2022. The retraction is under embargo until that time.

A new catalyst design enables unprecedented control over the modification of fatty acid derivatives that opens the door to creating useful substances in a green and efficient manner.

Hokkaido University WPI-ICReDD researchers developed a modular catalyst that can accurately modify fatty acid derivatives in a hitherto inaccessible position. This enables the efficient production of valuable compounds from a renewable bioresource, whereas before we had to either rely on petroleum-derived resources or use complicated and costly methods.

Many pharmaceuticals and plastics consist of a backbone that is essentially a chain of carbon atoms with modifications within their hydrocarbon framework. For their production, fatty acids are attractive raw material because they are easily accessible, renewable natural resources that consist of a chain of carbon atoms attached to a functional group called "carboxyl group." However, our ability to modify these chains has so far been limited to carbon atoms only one or two atoms away from the carboxyl group. Professor Masaya Sawamura of Hokkaido University's Institute for Chemical Reaction Design and Discovery (WPI-ICReDD) explains, "The chemical materials obtained in this way are limited to those with fairly simple structures, and in order to synthesize useful compounds, multi-step processes are necessary."

Building upon previous studies, Sawamura's group constructed a catalyst that consists of an iridium atom at its core and various modules that ensure that a fatty acid derivative -- fatty acid amide or ester in this case -- is precisely positioned in such a way that the C-H bond located three carbons away from the carboxyl group is modified. Moreover, while every C-H bond in a fatty acid derivative can be modified in two ways, giving compounds that are mirror images of one another, the catalyst developed by the team produces only one of the two possible products, which is an important attribute especially for drug development. To increase the breadth of possible modifications further, the researchers try to use different modules in their catalyst to change the way the substrate is positioned in the catalyst to allow different modifications.

In their article published in Science, the team demonstrated that their approach works with various substrates and can produce a large range of useful derivatives. In addition, they used quantum chemical calculations to investigate the precise structure and function of their catalyst driving the observed reactivity and selectivity. The results confirmed that the catalyst has a deep pocket that binds the substrate through interactions between one of its subunits and the carbonyl group of the substrate, and keeps it in place to facilitate the specific reaction -- a feature analogous to natural enzymes.

"The modular catalyst allowed the site-selective modification of fatty acid amides and esters, some of which are bioactive compounds. This simple, modular, and broadly applicable catalytic system allows the introduction of structural and chemical complexity to the hydrocarbon chain of readily available feedstock chemicals," says Ronald Reyes of the research team. Central to the success of these endeavors is a combination of experiments and computation. Sawamura says, "The accumulation of experimental knowledge is a source of great inspiration, but with the support of computer chemistry we can bring this to fruition in the near future."

In a pair of studies, researchers report the discovery and molecular pharmacology of stable, synthetic STING (stimulator of interferon genes) agonists that induce anticancer immune responses in mice. Combined, both studies' results represent progress towards clinically viable STING agonists for future cancer drugs and immunotherapeutic strategies. Activation of the innate STING immune pathway by natural agonists has been demonstrated to play an important role in antitumor immunity, which has made them an attractive target for use in cancer therapies. It's suggested that the administration of synthetic agonists of the STING pathway could be used to trigger de novo anticancer immune responses that can control tumor growth or enhance the outcome of cancer treatments like PD-1 blockade immunotherapy. However, the development of STING agonists for drug development has been challenging and largely limited by the inherent instability of the molecules involved. Here, Emily Chin and colleagues and Bo-Sheng Pan and colleagues, respectively, report on the discovery of stable STING agonists that show antitumor activity in preclinical cancer models. Chin et al. describe SR-717 - a stable, non-nucleotide small molecule STING agonist that functions similarly to the natural STING ligand cGAMP. According to these authors, SR-717 demonstrated robust anti-tumor activities in a mouse model of melanoma. Building on these findings, Pan et al. developed an agonist capable of pharmacologically activating the STING immune pathway through an orally administered drug. When tested in mouse models, the authors found that it was able to induce tumor regression and improve checkpoint blockade therapy. "Non-nucleotide small-molecule STING agonists that can be administered systemically may represent an attractive approach for targeting this pathway and have the potential to transform the therapeutic landscape once optimized," write Thomas Gajewski and Emily Higgs in a related Perspective.

Published in the highly prestigious journal Science, a new study has shed light on a cellular process that occurs in the retinas of people with diabetic retinopathy. This discovery could lead to the development of a treatment for this serious complication of diabetes. The research was led by Dr. Przemyslaw (Mike) Sapieha and Dr. François Binet in collaboration with Dr. Frédérick Antoine Mallette and Dr. Flavio Rezende of the Centre de recherche de l'Hôpital Maisonneuve-Rosemont (CR-HMR), which is part of the Centre intégré universitaire de santé et de services sociaux de l'Est-de-l'Île-de-Montréal, and Dr. Jean-Sébastien Joyal of the CHU Sainte-Justine Research Centre, affiliated with Université de Montréal and also with Dr. Jean-François Côté of the Montreal Clinical Research Institute (IRCM).

Diabetic retinopathy is characterized by vascular degeneration and later the formation of abnormal blood vessels in the retina. This vascular proliferation compromises the nerve cells that carry information from the eyes to the brain.

The study demonstrates that to stop abnormal vascular proliferation, blood vessels apply a series of molecular "brakes" that become activated in a way similar to an accelerated version of natural cellular aging. Collectively, these mechanisms culminate in a process called cellular senescence, which eventually causes tissue scarring in the retina.

When in senescence mode, blood vessels produce inflammatory molecules that become targets of immune cells called neutrophils. Although thought to be the immune system's first responders, the study shows that neutrophils arrive in the retina later on to help clean and remodel damaged blood vessels. They do this through an unconventional cellular mechanism of releasing neutrophil extracellular traps (or NETS) made up of their own DNA onto diseased blood vessels.

More broadly, the results of this study imply that the destruction of senescent blood vessels leads to beneficial vascular remodeling. The study therefore provides insight into the general function of endothelial cells and how they predispose older populations to complications such as myocardial infarction, atherosclerosis and strokes.

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. 

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.

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.

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.

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.

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.

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.