Culture

Residents of U.S. counties with more social connections (measured as Facebook friends) to China or Italy - the first countries to report major COVID-19 outbreaks - were more likely to adhere to social distancing restrictions at the onset of the pandemic, according to a new study. The findings suggest that social networks supplied pandemic-related information that significantly influenced individual behavior. However, social ties also could have negative effects on pandemic-related behavior. For instance, areas within the U.S. with more connections to counties with low education levels, high proportions of 2016 Trump voters, and high fractions of people who deny the existence of climate change experienced less adherence to mobility restrictions during the early pandemic. Previous research suggests online social connections may act as warning systems during natural disasters and can impact personal health decisions by spreading both facts and misinformation. To explore the role of these connections in the context of COVID-19-era social distancing, Ben Charoenwong and colleagues measured social connectedness between U.S. counties and foreign countries using aggregated, anonymized data from Facebook's Social Connectedness Index. The researchers combined this data with anonymized, county-level mobile phone location data that served as a proxy for adherence to social distancing measures between February 1 and March 30, 2020. They found that a one-standard-deviation increase in social connections with China or Italy correlated with a nearly 50% increase in the effectiveness of mobility restrictions. The authors also conclude that differences in how effectively Democrats and Republicans adhere to social distancing arise from discrepancies in the information they receive (facilitated by their social connections) rather than due to biases in how they interpret that information. "This finding has important policy implications, as it suggests changes in the information environment can boost the effectiveness of non-pharmaceutical interventions," the authors write.

LA JOLLA, CA--Through intricate experiments designed to account for sex-specific differences, scientists at Scripps Research have collaborated to zero in on certain changes in the brain that may be responsible for driving alcohol abuse among people with post-traumatic stress disorder, or PTSD.

In studies with rodents, researchers found that males and females exhibit their own distinct symptoms and brain features of PTSD and alcohol use disorder. Such differences are not typically accounted for in laboratory-based studies yet could lead to more successful clinical treatments.

The findings, published in Molecular Psychiatry, also present a new model for identifying biomarkers that may indicate a person with PTSD is more likely to develop alcohol use disorder.

"Having PTSD significantly increases the risk of developing alcohol use disorder, as individuals use alcohol to cope with stress and anxiety. Yet the underlying biology of comorbid disorders is generally not well understood," says Dean Kirson, PhD, a postdoctoral fellow in neurophysiology in the lab of professor Marisa Roberto, PhD, and a co-lead author with Michael Steinman, PhD. "We hope our new knowledge of sex-specific changes in the brain will help propel the development of more targeted treatments."

About 7 percent to 8 percent of the country's population will have PTSD at some point in their life, according to the U.S. Department of Veterans Affairs. Causes include combat exposure, physical abuse, an accident or other forms of trauma. Alcohol abuse disorder is also common, affecting some 15 million people in the United States. Those with stress and anxiety disorders such as PTSD are not only more likely to abuse alcohol, but also have increased alcohol withdrawal symptoms and relapse risk.

"Most people know or will know someone struggling with one or both of these disorders and may try to help them. However, there are very few effective treatments currently," Roberto says. "Both are complex disorders that affect similar brain circuitry. My lab has been studying addiction and stress separately, so here we teamed up with the Zorrilla lab to apply a novel translationally-relevant behavioral model to examine what changes occur when these disorders are comorbid."

The joint study between Roberto and Eric Zorrilla, PhD--who are co-senior authors--examined behavior, sleep patterns, inflammatory immune responses and levels of a neurotransmitter known as GABA (short for gamma-Aminobutyric acid), which lowers anxiety and increases feelings of relaxation and is a common feature of alcohol dependence.

For both male and female rats, traumatic stress and alcohol exacerbated other behaviors common in PTSD, such as social avoidance startle reactions and defensive behavior. Those who were identified as "drinking-vulnerable" prior to trauma most strongly showed avoidance of trauma-reminiscent places.

However, the scientists noted key differences in how males and females behave following trauma and saw markedly different patterns of GABA signaling. For example, males showed increased GABA receptor function, while females showed increased GABA release.

"This may be important because there is growing awareness that medicines could potentially have different levels of effectiveness in male and female patients and understanding the biology that explains why these differences exist could improve outcomes," Steinman says.

The team also found that males exhibited an immune-based biomarker--small proteins known as cytokines, which are secreted by immune cells--that determined vulnerability to alcohol use disorder. The females did not.

"We identified profiles of specific cytokines, many not previously linked to stress behaviors, that strongly related to poor drinking outcomes," says Zorilla, associate professor

In the Department of Molecular Medicine. "These may be important clinically or even mechanistically, but they were unique to males, so we have work ahead of us to find similar biomarkers for females."

The Roberto and Zorrilla labs plan to conduct additional research into the mechanisms behind the biological changes they observed and test which brain systems can be targeted to treat both PTSD and alcohol abuse.

"We also plan to further investigate the role of the immune system in these disorders," Roberto says. "These distinct biomarkers may aid in targeted treatment."

LA JOLLA, CA--A team led by scientists at Scripps Research has developed a theoretical approach that could ease the process of making highly complex, compact molecules.

Such molecules are often found in plants and other organisms, and many are considered desirable starting points for developing potential new drugs. But they also tend to be highly challenging for chemists to construct and modify in the lab--a process called synthesis.

The team used computer modeling and a theoretical framework centered on the concept of "information density" to illuminate chemistry principles underlying their landmark 2019 synthesis of the molecule bilobalide, which is produced in the leaves of the ginkgo tree, Ginkgo biloba. Bilobalide is a particularly complex and compact molecule that has shown promise as a potential neurological or psychiatric drug.

The scientists believe that the theoretical fruits of their new study, published in the Journal of the American Chemical Society, will enable chemists to devise more efficient syntheses of such challenging natural molecules--potentially opening up a new realm of powerfully bioactive compounds for development into medicines and other products.

"When we initially achieved our synthesis of bilobalide, we were essentially following our intuition, but in this new study we dug down to understand how the chemistry actually works and developed principles that we think can be applied to other challenges in organic synthesis," says Ryan Shenvi, PhD, a professor of chemistry at Scripps Research and the senior author of the study.

Creating a valuable natural compound

Bilobalide--which evolved in the ginkgo tree, likely to protect its leaves from insects--blocks an insect nerve-cell receptor called RDL. The fact that the molecule kills insects yet seems quite safe in mammals and dissipates quickly in the environment has attracted interest for safe crop protection.

Bilobalide holds strong promise for medicinal use, with evidence that it's relatively safe for humans. It blocks human brain-cell receptors called GABAA receptors, which are evolutionary cousins of insect RDL receptors. An intriguing 2007 study found that the compound could reverse cognitive and memory deficits in mice with a neurological condition modeling human Down syndrome, while other studies have suggested it may protect brain cells from certain kinds of harm.

Although natural bilobalide is synthesized by specialized enzymes in the ginkgo tree's cells, chemists would like to be able to make it in the lab with organic chemistry techniques. In this way, they could obtain large quantities of the compound and modify it to explore and optimize its properties.

But the synthesis of bilobalide has always been a major challenge for scientists, because the molecule packs a relatively complex set of atoms--including eight reactive oxygens--into an odd and highly compact chemical structure. If they could overcome that challenge, chemists would have a way to make molecules of potentially enormous value.

"When you have complexity that is condensed to that extent, you start to see interesting emergent properties," Shenvi says.

'Information density' brings deep understanding

In the study, Shenvi and his colleagues evaluated their 11-step synthesis of bilobalide, achieved in 2019, as well as two longer bilobalide syntheses that had been published previously.

With the help of computational modeling from collaborator Kendall Houk, PhD, the Saul Winstein Distinguished Research Chair in Organic Chemistry at UCLA, and a formal theory of "molecular information content" published in 2016 by German researcher Thomas Böttcher, they developed a concept of "information density"--essentially, complexity divided by molecular volume--and used that to analyze the bilobalide syntheses.

Their analysis showed that bilobalide, even compared with other naturally derived, compact and biologically active molecules, has a very high information density, and that its information content comes principally from its oxygen atoms and asymmetric carbon backbone.

The work revealed that the Shenvi lab's synthesis of bilobalide was efficient due to fragment coupling--merging already-complex oxygen-containing molecules--and then making careful modifications to overcome the unusual emergent properties of the system.

The chemistry principles the team developed make sense of their bilobalide synthesis and its greater efficiency over prior syntheses, but are also applicable to many other unsolved problems involving natural-molecule synthesis, the researchers say.

As part of the work, co-author Stefano Forli, PhD, wrote a computer script in the Python coding language to automate the calculation of molecular information, which can be otherwise laborious, at the rate of more than 100,000 molecules per minute. (The script is available for download.) Forli is assistant professor in Scripps Research's Department of Integrative Structural and Computational Biology.

Collaborating investigator Marisa Roberto, PhD, professor in the Department of Molecular Medicine at Scripps Research, studied the activity of bilobalide and another information-dense molecule, jiadifenolide, which Shenvi's team also recently synthesized. In rodent studies, she found that both bilobalide and jiadifenolide showed promise as relatively potent and safe GABAA blockers, suggesting the potential for being translated into drugs for psychiatric conditions involving abnormal GABAA activity.

"The GABA system is dramatically altered in neuropsychiatric disorders such as alcoholism and other forms of addiction, for which one or both of these compounds might one day prove useful," Roberto says.

BOSTON - For the first time, researchers have successfully created airway basal stem cells in vitro from induced pluripotent stem cells by reprogramming blood cells taken from patients. Given that airway basal cells are defined as stem cells of the airways because they can regenerate the airway epithelium in response to injury, this study may help accelerate research on diseases impacting the airway, including COVID-19, influenza, asthma and cystic fibrosis. Led by researchers at the Center for Regenerative Medicine at Boston Medical Center and Boston University (CReM), in collaboration with The University of Texas Health Science Center at Houston (UTHealth), these findings represent a critical first step towards airway regeneration, which will advance the field of regenerative medicine as it relates to airway and lung diseases.

Published in Cell Stem Cell, the novel study outlines how to efficiently generate and purify large quantities of airway basal stem cells using patient samples. This allows for the development of individual, disease-specific airway basal stem cells in a lab that can be used to develop disease models, which may ultimately lead to drug development and a platform in which targeted drug approaches can be tested. The study's findings and cells will be shared freely given the CReM's "Open Source Biology" philosophy, or sharing of information and findings that will help advance science across the globe.

"Simply put, we have developed a way to reproduce patient-specific airway basal cells in the lab, with the ultimate goal of being able to regenerate the airway for patients with airway diseases," said Finn Hawkins, MB, BCh, a pulmonologist and physician-scientist at Boston Medical Center, principal investigator in the CReM and the Pulmonary Center and the study's first author.

"These results could lead to a better understanding, and therefore treatments for, a variety of airway diseases," said Shingo Suzuki, PhD, co-first author and post-doctoral researcher at UTHealth. For example, cystic fibrosis is caused by a genetic mutation that is present in all of the airway cells. "If we could make pluripotent stem cells using a sample from a patient who has cystic fibrosis, correct the mutation and replace the defective airway cells with corrected airway basal cells that are otherwise genetically identical, we might eventually be able to cure the disease, and other diseases in the future using this same technology," added Hawkins.

Induced pluripotent stem cells are the master stem cells that can produce any cell or tissue in the human body. They are created by reprogramming a human sample, such as a drop of blood, into a population of cells that are similar to embryonic stem cells, including the ability to form different cell types within organs. For this study, the researchers established methods to generate an airway stem cell population, basal cells in the laboratory. These are an important cell type in human airways that maintain the lining of cells in the airway, including the cells the make mucus and those that propel the mucus upwards and out of the lungs.

The researchers first engineered induced pluripotent stem cells with a genetic sequence encoding a fluorescent protein that would allow them to visualize, track and purify basal cells if present. Then, the researchers turned to studies of the embryo and prior work in this field to determine how basal form as the lungs develop. By manipulating induced pluripotent stem cells with a series of steps aimed to simulate what happens during lung development the researchers successfully generated cells that were highly similar to human airway basal cells in terms of their appearance, the genes they expressed and most importantly, their ability to both proliferate and form the other cell types of the airway. The cells, termed ibasal cells, were able to regenerate an airway in vivo using a rodent trachea model.

The resulting ibasal cells, made from patients with a variety of lung diseases, were also able to model the airway diseases affecting those patients, including the mucus metaplasia that is characteristic of asthmatic airways, the chloride channel dysfunction that causes cystic fibrosis, and the defects in beating of the cilia that causes the disease primary ciliary dyskinesia. This approach will enable future opportunities to study these genetic changes, and how to reverse them in order to cure the disease in humans. From a practical perspective, ibasal cells grow well in special culture conditions in a lab, allowing them to be made in large numbers, and patient specific basal cells can be grown, frozen for future work, and shared with the broader research community.

"We demonstrated the potential of these ibasal cells to model both human development and disease, providing evidence of their capacity to regenerate airway epithelium," said Hawkins, who is also an assistant professor of medicine at Boston University School of Medicine. "We expect this will be a significant breakthrough and will contribute to new insights and treatment options for airway diseases, as our results have overcome several important hurdles currently limiting progress in the field."

A new method for verifying a widely held but unproven theoretical explanation of the formation of stars and planets has been proposed by researchers at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL). The method grows from simulation of the Princeton Magnetorotational Instability (MRI) Experiment, a unique laboratory device that aims to demonstrate the MRI process that is believed to have filled the cosmos with celestial bodies.

Cosmic dust

The novel device, designed to duplicate the process that causes swirling clouds of cosmic dust and plasma to collapse into stars and planets, consists of two fluid-filled concentric cylinders that rotate at different speeds. The device seeks to replicate the instabilities that are thought to cause the swirling clouds to gradually shed what is called their angular momentum and collapse into the growing bodies that they orbit. Such momentum keeps the Earth and other planets firmly within their orbits.

"In our simulations we can actually see the MRI develop in experiments," said Himawan Winarto, a graduate student in the Princeton Program in Plasma Physics at PPPL and lead author of a paper in Physical Review E interest in the subject began as an intern in the University of Tokyo-Princeton University Partnership on Plasma Physics while an undergraduate at Princeton University.

The suggested system would measure the strength of the radial, or circular, magnetic field that the rotating inner cylinder generates in experiments. Since the strength of the field correlates strongly with expected turbulent instabilities, the measurements could help pinpoint the source of the turbulence.

"Our overall objective is to show the world that we've unambiguously seen the MRI effect in the lab," said physicist Erik Gilson, one of Himawan's mentors on the project and a coauthor of the paper. "What Himawan is proposing is a new way to look at our measurements to get at the essence of MRI."

Surprising results

The simulations have shown some surprising results. While MRI is normally observable only at a sufficiently high rate of cylinder rotation, the new findings indicate that instabilities can likely be seen well before the upper limit of the experimental rotation rate is reached. "That means speeds much closer to the rates we are running now," Winarto said, "and projects to the rotational speed that we should aim for to see MRI."

A key challenge to spotting the source of MRI is the existence of other effects that can act like MRI but are not in fact the process. Prominent among these deceptive effects are what are called Rayleigh instabilities that break up fluids into smaller packets, and Ekman circulation that alters the profile of fluid flow. The new simulations clearly indicate "that MRI, rather than Ekman circulation or Rayleigh instability, dominates the fluid behavior in the region where MRI is expected," Winarto said.

The findings thus shed new light on the growth of stars and planets that populate the universe. "Simulations are very useful to point you in the right direction to help interpret some of the diagnostic results of experiments," Gilson said. "What we see from these results is that the signals for MRI look like they should be able to be seen more easily in experiments than we had previously thought."

The CRISPR Journal announces the publication of its October 2020 issue. The Journal is dedicated to validating and publishing outstanding research and commentary on all aspects of CRISPR and gene editing, including CRISPR biology, technology, and genome editing, and commentary and debate of key policy, regulatory, and ethical issues affecting the field. The Journal, led by Editor-in-Chief Rodolphe Barrangou, PhD (North Carolina State University) and Executive Editor Dr. Kevin Davies, is published bimonthly in print and online. Visit The CRISPR Journal website for more information.

This press release is copyright Mary Ann Liebert, Inc. Its use is granted only for journalists and news media receiving it directly from The CRISPR Journal. For full-text copies of articles or to arrange interviews with Dr. Barrangou, Dr. Davies, authors, or members of the editorial board, contact Kathryn Ryan at the Publisher.

1. Heritable Human Genome Editing: The Community Responds
In September 2020, a major report -- Heritable Human Genome Editing (HHGE) -- was published by the National Academies of Sciences and the UK's Royal Society. The report, triggered by the outrage that accompanied the news of the birth of genetically edited "CRISPR babies" in 2018 -- outlined a narrow translational pathway for the safe, responsible use of human embryo editing.

In this multi-author Perspective, The CRISPR Journal invited 50 experts from the world of genetics, CRISPR, bioethics, law and other areas to share their personal reactions to the HHGE report. Three dozen offered candid comments, which have been collated into this Perspective. Among the experts offering their reactions are Nobel laureate Jennifer Doudna, Art Caplan, George Church, Eric Topol, Bob Cook-Deegan, Laura Hercher, Kiran Musunuru, Hank Greely, David Liu, and Feng Zhang. While many applaud the findings of the HHGE commission, several recurring reservations were documented, including lack of ethical considerations, societal consensus, health disparities, and regulatory questions.

Contact: Kevin Davies (The CRISPR Journal)

2. Global Regulation and Policy Landscape of HHGE
In an original research article, Marcy Darnovsky, Francoise Baylis, and colleagues present the most comprehensive survey to date of global laws and regulations regarding hereditary human genome editing (HHGE). The authors surveyed 106 countries, gathering policy documents from 96 of them pertaining to regulations or guidelines for the use of genome editing on early-stage human embryos (or gametes).

Most countries do not have policies that specifically address the use of genetically modified in vitro embryos in laboratory research. 23 countries prohibit this research while 11 permit it. Meanwhile, the authors found that 75 of the 96 countries prohibit the use of heritable genome editing (five countries provide certain exceptions). No country explicitly permits HHGE.

Contact: Marcy Darnovsky (Center for Genetics and Society, Berkeley CA) and Francoise Baylis (Dalhousie University, Nova Scotia, Canada)

3. A Pathway for HHGE: An Interview with Dame Kay Davies
Last month, the National Academies/Royal Society commission on Heritable Human Genome Editing (HHGE), co-chaired by two eminent geneticists, Rockefeller University president Rick Lifton and University of Oxford professor Dame Kay Davies, issued its long-awaited report on the path forward for HHGE.

In an exclusive interview in this issue of The CRISPR Journal, commission co-chair Dame Kay Davies offers a glimpse behind the scenes as she discusses how the commission's report was produced. She summarizes the chief recommendations and addresses some of the chief regulatory and ethical concerns that have been raised. (The full interview can be heard as Episode 17 of Guidepost, The CRISPR Journal's flagship podcast series.)

Contact: Kay E. Davies (University of Oxford)

MIAMI--As the world enters a next wave of the ongoing COVID-19 pandemic, we are aware now more than ever of the importance of a healthy immune system to protect ourselves from disease. This is not only true for humans but corals too, which are in an ongoing battle to ward off deadly diseases spreading on a reef.

A new study led by researchers at the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science looked at the immune system of elkhorn coral (Acropora palmata), an important reef-building coral in the Caribbean, to better understand its response to diseases such as white band disease and rapid tissue loss.

In the experiment, healthy corals were grafted to diseased ones. After one week, the corals were analyzed to study the coral's overall gene expression in response to disease, if they exhibited an immune response, and whether there were different signatures of gene expression for corals that didn't show signs of disease transmission. The researchers found that A. palmata has a core immune response to disease regardless of the type of disease, indicating that this particular coral species mounts an immune response to disease exposure despite differences in the disease type and virulence.

"Our results show that elkhorn coral is not immunocompromised but instead is actually actively trying to fight off disease," said Nikki Traylor-Knowles, an assistant professor of marine biology and ecology at the UM Rosenstiel School and senior author of the study. "This gives me hope that the corals are fighting back with their immune system."

Based upon these findings, the researchers suggest that corals that did not get disease may have tougher epithelia, a protective layer of cells covering external surfaces of their body. And, that the symbiotic dinoflagellate, Symbiodiniaceae, that live inside corals did not have differences in gene expression in response to disease, but over the course of the two-year study did develop differences.

Coral disease is considered one of the major causes of coral mortality and disease outbreaks are expected to increase in frequency and severity due to climate change and other man-made stressors. The Caribbean branching coral Acropora palmata which has already seen an 80 percent decrease on reefs primarily due to disease, which has resulted in them being classified as threatened under the US Endangered Species Act.

"These corals are keystone species for Florida reefs, so understanding that their immune systems are active is an important component that can be useful for protecting reefs," said Traylor-Knowles.

Plant biology researchers at the University of Illinois and computer scientists at the University of California Irvine have developed a new method of fossil pollen identification through the combination of super-resolution microscopy and machine learning. The team, led by Dr. Surangi Punyasena and Ms. Ingrid Romero (associate professor and graduate student in Plant Biology, respectively), developed and trained three convolutional neural network models to identify fossil pollen specimens from an unknown group of legumes.

"The global fossil pollen record is one of the most abundant terrestrial records that we have," said Punyasena. "It's the record that preserves the history of environmental and ecosystem change for the last 470 million years." The pollen record is crucial for understanding how plant species evolved and dispersed globally. By reconstructing how different ecosystems and species have changed through time, we can better understand current plant relationships and better inform conservation and climate mitigation efforts.

However, correctly measuring and identifying the morphological features of a pollen grain can be incredibly difficult. "Much of the palynological record doesn't have biological identifications associated with it," explained Punyasena. "Many of the types that we know from deeper time (beyond the last 100 thousand years or so) are groups for which we don't have a definitive sense of their identity. The effort needed to classify these types has just been too great."

Traditional methods such as scanning electron and transmission electron microscopy destroy the sample and are very labor- and time-intensive. Airyscan, by comparison, is a light microscopy method that can see below the diffraction limit of light and can be used to non-destructively collect cross-sectional images from inside and outside of the pollen grain. "This method is very useful for samples that are not abundant," said Romero. "You can mount the grains on a slide and image them efficiently without damaging the sample."

This new approach allows researchers to train machine classification models using pollen from living plants and then confirm their fossil relatives, iteratively learning from each identification to differentiate among specimens that closely resemble one another. This allowed the team to recognize genera within a larger morphological grouping of fossil legume pollen for the first time. The trained models classified fossil specimens from western Africa and northern South America dating back to the Paleocene (66-56 million years ago), Eocene (56-34 million years ago) and Miocene (23-5.3 million years ago). The most accurate model used a combination of images from both the exterior and interior of the pollen grain and was able to correctly identify samples with 90.3% accuracy.

These results suggest that Airyscan microscopy and machine learning methods could not only aid in identification of unknown specimens, but also help to constrain the time of a plant group's origin or extinction. With more information about the relationships and distribution of pollen samples in deep time, researchers can better pinpoint when and where evolutionary changes occurred.

"We have seen a huge improvement in imaging capabilities and the power of computer vision algorithms. We have gotten to the point where these algorithms can interpret complex images in a very efficient and intelligent way, giving us usable identifications. That is the key difference and innovation of these models - it's the ability to train a system on pristine modern taxa and then use that system to identify unknown and often physically distorted fossil types," said Punyasena. "This approach replicates and extends the abilities of the human analyst."

When Dr. Stephen Smith of Seattle Children's Research Institute came down with muscle aches, gastrointestinal distress and a sudden loss of smell in late February, he suspected he had COVID-19. The testing criteria had yet to be expanded to include individuals with Smith's symptoms and so he did what many scientists with his expertise would do: he developed a way to test himself.

The fruits of his curiosity, now published in The Journal of Infectious Diseases, offer a reliable way to quantify whether an individual has neutralizing antibodies that could prevent the novel coronavirus from infecting cells using a method that is more broadly applicable than those currently available.

"If you think you've had COVID-19 and go to the doctor, they can test your blood and tell you whether or not you have antibodies to COVID-19, but that doesn't tell you whether your antibodies are any good at functionally blocking the virus from binding to cells," Smith said. "There are tests on the market now that can tell you that, but they are expensive and take a long time to get results. We wanted to develop a way to give you additional information about your immune status without all the barriers that make it difficult to use in a community setting."

The newly developed diagnostic could have a range of potential commercial applications from broad community testing to assessing vaccine responses and screening for convalescent plasmas that have particularly high levels of neutralizing antibodies as a potential treatment.

Cell-free test looks at protein interactions

The novel coronavirus enters cells when the viral spike protein binds to the ACE2 protein on the surface of human cells. Neutralizing antibodies that block this binding are thought to contribute to immunity to the virus in people who recover from COVID-19.

Smith applied a technique called immunoprecipitation detected by flow cytometry (IP-FCM) to study the interactions between the proteins and to look for evidence that antibodies were inhibiting the interaction and blocking the virus from binding to cells. Instead of relying on live cells and viruses like other available blood tests, IP-FCM uses recombinant - or lab-made - proteins and instruments commonly available in commercial serological labs.

"Other tests that provide insight into immunity work by taking antibodies from your blood and mixing them together with a virus and then exposing that mixture to live cells. Three days later they can determine immunity based on whether your blood prevented the viruses from infecting the cells or not," Smith said. "Our cell-free test can provide that same information overnight."

Collaborative science launches innovative study

Smith is among a small group of scientists in the U.S. who have pioneered IP-FCM to study the interactions between proteins. His lab in Seattle Children's Center for Integrative Brain Research uses IP-FCM to uncover new treatments for autism by studying the more than 100 genetic variations known to contribute to the condition.
To apply his expertise to the current pandemic, Smith collaborated with Drs. Lisa Frenkel and Whitney Harrington from the research institute's Center for Global Infectious Global Disease Research who are following a community cohort of Seattle Children's employees who were never hospitalized and had recovered from mild to moderate COVID-19. The researchers hope by tracking their recovery and taking blood samples over time as part of the Seattle Children's Recovered SARS2 Cohort study they can shed light on the immune responses to the novel coronavirus.

Funding in part by Seattle Children's COVID-19 Research Fund helped Smith design and launch the study.

Using IP-FCM, Smith tested the blood samples from 24 cohort participants. The test showed that 92% of the participants had antibodies to the novel coronavirus at an average of a little over a month post-infection. Results were validated with 30 control samples.

"Not only did the participants have antibodies, but our test also showed that their antibodies were pretty effective at neutralizing the binding between the spike protein and the cell's receptor," he said. "It's consistent with other studies from cell-based tests showing that people who get COVID do make neutralizing antibodies."

Interestingly, when researchers looked at the test results against other data gathered from the cohort, they found that those who mounted a fever had higher levels of antibodies. The research team also plans to retest the samples to see how antibody levels change over time.

"It's going to be very important to look at people over a longer time period to track their antibody levels and whether or not they get re-infected," Smith said. "Until we do those studies, we really don't know how these clinical measures of antibody neutralization relate to susceptibility in the real world."

Identifying new drug candidates for COVID-19

In addition to exploring opportunities to commercialize the diagnostic, Smith and his team are now using the test to rapidly screen thousands of approved drugs that could potentially interfere with the binding between ACE2 and the spike protein.

Lab manager, Edward Gniffke, and Stanford University undergraduate and summer intern, Kaleb Tsegay, helped run the initial screen that could potentially identify drugs capable of preventing or treating COVID-19.

"We already have some compounds that look like they are inhibiting, which is pretty exciting," Smith said. "This first line screen will help us pinpoint the most promising agents for further tests."

CAMBRIDGE, MA -- People with amyotrophic lateral sclerosis (ALS) suffer from a gradual decline in their ability to control their muscles. As a result, they often lose the ability to speak, making it difficult to communicate with others.

A team of MIT researchers has now designed a stretchable, skin-like device that can be attached to a patient's face and can measure small movements such as a twitch or a smile. Using this approach, patients could communicate a variety of sentiments, such as "I love you" or "I'm hungry," with small movements that are measured and interpreted by the device.

The researchers hope that their new device would allow patients to communicate in a more natural way, without having to deal with bulky equipment. The wearable sensor is thin and can be camouflaged with makeup to match any skin tone, making it unobtrusive.

"Not only are our devices malleable, soft, disposable, and light, they're also visually invisible," says Canan Dagdeviren, the LG Electronics Career Development Assistant Professor of Media Arts and Sciences at MIT and the leader of the research team. "You can camouflage it and nobody would think that you have something on your skin."

The researchers tested the initial version of their device in two ALS patients (one female and one male, for gender balance) and showed that it could accurately distinguish three different facial expressions -- smile, open mouth, and pursed lips.

MIT graduate student Farita Tasnim and former research scientist Tao Sun are the lead authors of the study, which appears today in Nature Biomedical Engineering. Other MIT authors are undergraduate Rachel McIntosh, postdoc Dana Solav, and research scientist Lin Zhang. Yuandong Gu of the A*STAR Institute of Microelectronics in Singapore and Nikta Amiri, Mostafa Tavakkoli Anbarani, and M. Amin Karami of the University of Buffalo are also authors.

A skin-like sensor

Dagdeviren's lab, the Conformable Decoders group, specializes in developing conformable (flexible and stretchable) electronic devices that can adhere to the body for a variety of medical applications. She became interested in working on ways to help patients with neuromuscular disorders communicate after meeting Stephen Hawking in 2016, when the world-renowned physicist visited Harvard University and Dagdeviren was a junior fellow in Harvard's Society of Fellows.

Hawking, who passed away in 2018, suffered from a slow-progressing form of ALS. He was able to communicate using an infrared sensor that could detect twitches of his cheek, which moved a cursor across rows and columns of letters. While effective, this process could be time-consuming and required bulky equipment.

Other ALS patients use similar devices that measure the electrical activity of the nerves that control the facial muscles. However, this approach also requires cumbersome equipment, and it is not always accurate.

"These devices are very hard, planar, and boxy, and reliability is a big issue. You may not get consistent results, even from the same patients within the same day," Dagdeviren says.

Most ALS patients also eventually lose the ability to control their limbs, so typing is not a viable strategy to help them communicate. The MIT team set out to design a wearable interface that patients could use to communicate in a more natural way, without the bulky equipment required by current technologies.

The device they created consists of four piezoelectric sensors embedded in a thin silicone film. The sensors, which are made of aluminum nitride, can detect mechanical deformation of the skin and convert it into an electric voltage that can be easily measured. All of these components are easy to mass-produce, so the researchers estimate that each device would cost around $10.

The researchers used a process called digital imaging correlation on healthy volunteers to help them select the most useful locations to place the sensor. They painted a random black-and-white speckle pattern on the face and then took many images of the area with multiple cameras as the subjects performed facial motions such as smiling, twitching the cheek, or mouthing the shape of certain letters. The images were processed by software that analyzes how the small dots move in relation to each other, to determine the amount of strain experienced in a single area.

"We had subjects doing different motions, and we created strain maps of each part of the face," McIntosh says. "Then we looked at our strain maps and determined where on the face we were seeing a correct strain level for our device, and determined that that was an appropriate place to put the device for our trials."

The researchers also used the measurements of skin deformations to train a machine-learning algorithm to distinguish between a smile, open mouth, and pursed lips. Using this algorithm, they tested the devices with two ALS patients, and were able to achieve about 75 percent accuracy in distinguishing between these different movements. The accuracy rate in healthy subjects was 87 percent.

Enhanced communication

Based on these detectable facial movements, a library of phrases or words could be created to correspond to different combinations of movements, the researchers say.

"We can create customizable messages based on the movements that you can do," Dagdeviren says. "You can technically create thousands of messages that right now no other technology is available to do. It all depends on your library configuration, which can be designed for a particular patient or group of patients."

The information from the sensor is sent to a handheld processing unit, which analyzes it using the algorithm that the researchers trained to distinguish between facial movements. In the current prototype, this unit is wired to the sensor, but the connection could also be made wireless for easier use, the researchers say.

The researchers have filed for a patent on this technology and they now plan to test it with additional patients. In addition to helping patients communicate, the device could also be used to track the progression of a patient's disease, or to measure whether treatments they are receiving are having any effect, the researchers say.

"There are a lot of clinical trials that are testing whether or not a particular treatment is effective for reversing ALS," Tasnim says. "Instead of just relying on the patients to report that they feel better or they feel stronger, this device could give a quantitative measure to track the effectiveness."

'Foreign disinformation' social media campaigns are linked to falling vaccination rates, reveals an international time trends analysis, published in the online journal BMJ Global Health.

Every 1 point increase in effort is tied to an average 2% drop in annual coverage around the globe, and a 15% increase in the number of negative tweets about vaccination, shows the study, which forms part of a BMJ Collection on Democracy and Health published for the World Health Summit this weekend.

Last year, the World Health Organization (WHO) listed vaccine hesitancy--reluctance or refusal to be vaccinated because of safety concerns---as one of the top 10 threats to world health.

While vaccine hesitancy isn't new, the proliferation of 'anti-vaxx' messaging on social media is of particular public health concern, given that vaccination is seen as a key route out of the current coronavirus pandemic, say the researchers.

Deliberate 'disinformation' campaigns by foreign agencies on social media also have their part to play, they add.

To gauge the impact of social media use and foreign disinformation campaigns on vaccine hesitancy around the world, the researchers analysed two different dimensions of social media activity for up to 190 countries.

These were: the public use of Twitter to organise action/resistance; and the amount of tweets expressing negative sentiments about vaccines.

They also drew on national survey data about public attitudes to vaccination safety and annual vaccination rates for the 10 most commonly reported vaccine doses between 2008 and 2018.

They used recognised analytical tools to measure sentiment (Polyglot Python Library); public use of social media to organise (Digital Society Project or DSP); foreign sources of disinformation (Varieties of Democracy Institute expert network + DSP); public attitudes to vaccine safety (2019 Wellcome Global Monitor).

They also logged measures of GDP (gross domestic product) per head of the population for each country and levels of internet usage.

Analysis of all the data revealed that the prevalence of foreign disinformation activity was "highly statistically and substantively significant" in predicting a drop in average vaccination rates.

A one-point shift upwards in the five-point disinformation scale was associated with an average fall in the annual vaccination rate of 2 percentage points, and a cumulative drop of 12 percentage points across the decade.

A belief that vaccines are inherently unsafe was associated with organisation of action/resistance on social media: and the more organisation on social media, the greater was the level of belief that vaccines are unsafe.

Foreign disinformation was also associated with negative social media activity about vaccination, boosting the number of negative vaccine tweets by 15%, on average.

While the study is unique, it wasn't able to specify the particulars of foreign disinformation campaigns or the prevalence of anti-vacccination propaganda, the researchers acknowledge.

What's more, Twitter isn't used in every country, and the survey data were only available at one point in time.

Nevertheless, write the researchers: "Foreign disinformation campaigns are robustly associated with declines in [average] vaccination rates. The use of social media to organise offline action is highly associated with an increase in public belief in vaccines being unsafe.

"Both of these findings suggest that combating disinformation and misinformation regarding vaccines online is critical to reversing the growth in vaccine hesitancy around the world."

They add: "These findings are especially salient in the context of the COVID-19 pandemic, given that the vaccines under development will require deployment globally to billions of people in the next year."

Public outreach and education campaigns will, of course, be needed, but they won't be enough by themselves to counter the tide of mistrust, they emphasise.

"First, governments must mandate that social media companies are responsible for taking down anti-vaccination content (whether originating from genuine domestic actors or foreign propaganda operations)," they advise.

"Second, foreign disinformation campaigns should be addressed at their source. A preponderance of such campaigns amplifying anti-vaccination content originate from within Russia or via pseudo-state actors informally associated with Russia," they warn.

None of this will be easy, they acknowledge, because it means reconciling the principles of free speech with the policing of social media for "damaging falsehoods," and persuading Russia to adopt a ceasefire on internet information warfare in the interests of the health of its own people.

But they conclude: "We urge policy makers to take the time before a COVID-19 vaccine is available for mass distribution as an opportunity for action against social media factors contributing to vaccine hesitancy."

Politicians are unlikely to be punished or rewarded for their failures or successes in managing the coronavirus pandemic at the next election, suggests an analysis of survey data from the US, the UK and India, published in the online journal BMJ Global Health.

This is despite the fact that most survey participants think health is a key policy area and that their government is to blame for the spread of COVID-19, shows the study, which forms part of a BMJ Collection on Democracy and Health published for the World Health Summit this weekend.

Health is often politicised, but it's not clear if public health issues influence public opinion and if these opinions might translate into voting behaviour.

The researchers reasoned that because it is global in scope and the focus of intense media interest, the COVID-19 pandemic therefore offers a unique opportunity to observe the interplay between public opinion and electoral politics.

How political leaders and parties have handled the pandemic has been front and centre of news coverage, suggesting that if public health matters to voting intentions, COVID-19 would seem to be a perfect storm, say the researchers.

To explore this further, they ran surveys on the health and economic impacts of the pandemic in the US, UK, and India during mid April to early June, recruiting nearly 3000 participants, half of whom came from the US.

The format of the survey involved revealing key facts about either the economic impact of the pandemic or the health impact (2 'treatment' groups), or revealing no key facts (comparison group).

Respondents were then asked questions designed to uncover attitudes towards their government, including its leader, and potential voting intentions if an election were held that day. They were also asked if they held their government responsible for the spread of COVID-19.

The economic facts covered the scale of job losses, overall shrinkage of the economy, and the impact on the stock market in each of the three countries. The health facts covered the numbers of projected hospital admissions, including the need for intensive/critical care, and the numbers of deaths in each of the countries, emphasising the lack of a cure or effective vaccine for COVID-19.

The researchers expected that compared with respondents in the comparison group, those in the two 'treatment' groups would either favour or disfavour the incumbent government and blame it for the pandemic.

But that's not what the responses indicated. More than 85% of respondents agreed that health was a key policy area for which their government had some responsibility (90%+ agree).

Yet while more than half the respondents thought their government was to blame for the spread of the pandemic, those given key facts about the pandemic were no more likely to favour or disfavour the incumbent government, or blame it for the pandemic, than those in the comparison group---what is known as a 'null' result.

The researchers acknowledge that they recruited many fewer people than they had hoped in the UK, and the survey platform they used is biased towards young men in all countries and, in the case of India, relatively more educated men, so unlikely to be completely nationally representative.

The surveys were also carried out some time before elections were expected--years in the case of the UK and India.

But they write: "the null findings contained in this study suggest that politicians are unlikely to be punished or rewarded for their failures or successes in managing COVID?19 in the next election."

They are tempted to conclude that public health issues have little influence on voter preferences in most election cycles. "It is not clear, for example, that the depression in life expectancies in the US, the continuing underperformance of the NHS in the UK, and the low?level of public sector health expenditure in India has had much impact on elections in those countries," they say.

"The urgency with which the COVID?19 pandemic has ripped through social, economic and political landscapes may challenge these complacencies - but only if [people en masse] make connections between the state of public health and what public officials can do," they suggest.

"If public health is politically inconsequential, this also raises questions about the impact of political institutions on health outcomes," they add.

Movement in animals is complex, especially in human beings. A variety of neurons coordinate the activity and inactivity of our muscles, and without that coordination we'd fall flat on our face when we went for a walk.

Scientists have known for quite some time how motor neurons in the spinal cord that activate muscles are organized to generate more forceful output, to transition from walking to jogging to running, for example. Little is known, however, about how spinal inhibitory interneurons work to inhibit, or silence, other neurons and related muscle groups in coordination with the active muscle groups across changing speeds.

Now a Northwestern University research team has discovered in a study of zebrafish that there is a very orderly relationship between when these critical inhibitory neurons are born, their participation in different speeds of movement and what part of a motor neuron they innervate. As a result of this compartmental setup, the amounts of inhibition received by the motor neurons are tuned to different speeds of movement.

Zebrafish is a model organism whose spinal cord works in a fashion similar to our own. Leaning more about the undulating movement of the swimming fish will allow scientists to better understand how humans walk.

The study will be published Oct. 23 by the journal Science.

"A better understanding of how circuits in the spinal cord are organized to coordinate movements puts us in a better position to repair things when damaged or diseased," said David McLean, corresponding author of the study.

"The fact that we see this pattern in the spinal cord, a relatively primitive part of the nervous system, and in fish, a relatively primitive vertebrate, means that nervous systems made use of this compartmental scheme to regulate activity much earlier than we would have expected," he said. "It's a bit like discovering parts for a combustion engine during an archaeological dig."

McLean is an associate professor of neurobiology in the Weinberg College of Arts and Sciences. He studies the development and functional organization of motor networks. With his research into how these networks control the direction and speed of movements, McLean hopes to reveal broad principles that help explain disorders impacting our capacity to move, such as Parkinson's disease, epilepsy and spinal injury.

"As neuroscientists, our job is to make sense of the enormous complexity we find in the nervous system that generates behavior," McLean said. "One way we do that is to look for patterns that give us a sense that there is an underlying logic -- an algorithm that bridges species and is useful in other parts of the brain. This, I think, is one such pattern."

In their study, McLean and his team used a number of cutting-edge approaches, including using lasers and fluorescent proteins to light up individual neurons and their connections in the transparent fish. They also used electrophysiology in genetically modified fish to characterize function in intact, behaving animals.

The researchers found that inhibitory neurons born first are active during the fastest movements and are most effective at silencing motor output by innervating motor neuron axons, closest to where activity is generated. Next to develop are interneurons active at intermediate speeds that strongly inhibit motor neuron cell bodies, followed by those active at slow speeds that weakly inhibit dendrites.

Collectively, the arrangement of inhibitory inputs in different structural compartments simplifies the process of ensuring appropriate patterns of motor output at different speeds, McLean said, since different cell types can provide a stronger or weaker 'veto' over motor output depending on when they are active.

"This compartmental pattern exists in other animals and brain regions, but using zebrafish we discovered clear functional consequences by watching the circuits develop, similar to understanding how a car works by following the assembly line," said Sandeep Kishore, first author of the study and a research associate in McLean's lab.

During early development of the zebrafish, inhibitory networks controlling the most forceful movements are the first to become functional, followed by those controlling more subtle, controlled movements.

"This makes some sense when you consider human development, where our first actions are kicking movements in the womb," McLean said. "Only later do we require and acquire finer motor skills."

CLEVELAND--More than 103,000 rental units spread across the city proper are potentially vulnerable to lead contamination because they were built before 1978 when lead paint was outlawed. According to a new study from Case Western Reserve University's Center on Urban Poverty and Community Development at the Jack, Joseph and Morton Mandel School of Applied Social Sciences, over one-third of these units are in poor condition and of very low market value. This can present the dual challenge of requiring potentially costly repairs in buildings where there is little equity to leverage financing, and results in potential risk of lead poisoning to children who may live in them.

Using a variety of public records--including assessed market value, sales, foreclosure and tax history, code violations, building permits and rental registry data--the researchers examined every rental property in the city from 2016-18 on factors related to the likelihood that the property could have lead-safety problems. Property owners were categorized according to whether they were companies or individuals, the number and types of properties they held and the property values and conditions represented in their portfolios.

"The issue is that the majority of families with young children in Cleveland rent homes in the private rental market," said Claudia Coulton, the study's co-author, a Distinguished University Professor and co-director of the poverty center. "Improving these properties--and working with these property owners-- is a key element in moving toward a lead-safe Cleveland."

"The majority of the city's rental housing stock carries a significant risk of lead exposure to children because of age, deferred maintenance and low-market value, so understanding the rental landscape is crucial," said Rob Fischer, an associate professor at the Mandel School and study co-author.

Key findings:

Single-family homes make up most of the city's rental properties, accounting for nearly half of all rental units. Another 24% of properties are two-family homes; 21% are small buildings (with three to 20 units); and 12% are large buildings (with more than 20 units).

Nearly two-thirds of Cleveland's rental properties are maintained in above average or good condition and have average market values, but the remainder are of relatively low value and in rather poor condition.

Among Cleveland landlords in 2018, more than 80% were listed as individual owners, owned only one property in the city of Cleveland and either lived or had a business address within Cuyahoga County. A significant proportion of the landlords (43%) had property that was classified as being in "bad condition" and/or of "very low market value" (29%).

Based on a combination over a dozen landlord characteristics, researchers divided the city's landlords into three categories: Type 1 were owners of single- or two-family homes in good condition and of average or above-average market value; Type 2 landlords owned mostly doubles in bad condition with low market value; and Type 3 landlords were larger operators, often corporate, holding properties of varying sizes and condition. These categories inform how best to engage and support different landlords.

Partnering with Lead Safe Cleveland Coalition, the research helps inform the continued implementation of the Lead Safe Home Fund, a first-of-its-kind, public-private partnership aimed at assisting landlords and tenants with accessing the resources they need to make housing lead safe throughout Cleveland, Fischer said.

The Lead Safe Home Fund will provide property owners and families with effective and equitable support for home repair and lead poisoning prevention. The Fund is structured to be flexible and nimble, with a five-year, $99.4 million target budget. CHN Housing Partners, a lender and the region's largest provider of affordable housing, will administer the home loans and grants.

"Our role is to help property owners--especially those 'mom-and-pop' landlords--improve the quality of the units they rent and get their Lead Safe Certification," said Kevin J. Nowak, executive director of CHN Housing Partners. "This research helps us better understand their assets and challenges. We are tailoring our grants, loans and incentives to meet property owners where they are, so that they can access the resources they need in a comprehensive, straight-forward way.

Regulators have failed to properly address patient safety on discharge from hospital in England, leaving the physical wellbeing and dignity of patients continuously at risk at a time when they should be returning safely home, finds new research.

The research, 'Leaving hospital: A step too far for risk-based regulation?' investigates the reasons for the lack of effective regulations from a legal standpoint. It was published in the journal, Medical Law Review* and was funded by the National Institute for Health Research Greater Manchester Patient Safety Translational Research Centre (GM PSTRC) which is a partnership between The University of Manchester and Salford Royal hospital.

Victoria Moore, who led the research, is from the centre's Safer Care Systems and Transitions theme, and said: "Being discharged from hospital can be a dangerous time for patients, but this is an area that regulators haven't recognised as a group and as such haven't paid much attention to. This leaves patients vulnerable. My research investigates why this is the case. The answer lies in the regulatory approach that dominates regulation within the NHS."

Risk-based regulation is the regulatory approach underpinning health and social care regulations in England. To be successful, this approach requires the risk to patient safety to be appropriately identified, fully understood and prioritised by all regulators involved.

Victoria continued: "Within healthcare regulation in England there are a number of regulators, so it is virtually impossible for all of them to have a unified understanding of the risk posed by discharge. This has resulted in a lack of action by any one regulator."

The research identifies that in hospital discharge, there are three main weaknesses in risk-based regulation and these have been created by the sheer number of regulators involved.

The first is when identifying risk, as regulators don't possess a complete overview of all relevant information. This is because of the limited information-sharing mechanisms between the regulators. Therefore, judgements have to be made about what information to share and with which regulator. This is problematic given that successful risk-based regulation is heavily dependent upon the availability of sufficient information to identify risks and inform decision-making.

The number of statutory regulators and the limited nature of information-sharing leads to a second important weakness; it's virtually impossible for all regulators to have a unified understanding of the risks posed by discharge from hospital. Risks will be understood based on the nature of information available, which will vary due to the number of regulators involved.

Finally, the research explains that successful risk-based regulation relies on being able to correctly prioritise risk. This can only happen if regulators have gathered enough information and all understand and agree the regulatory aims.

Victoria concludes: "The combination of the three weaknesses I've identified in my research means the risk posed to the safety of patients on discharge from hospital is neither uniformly recognised by the statutory regulators within the English NHS, nor sufficiently addressed. Professional regulators in particular appear to have a poor awareness of the risk and their role in addressing it. Until regulators can accurately identify this risk, build a unified understanding of its causes and consequences, and prioritise it appropriately, this unacceptable status quo will remain."

The Director of the Greater Manchester PSTRC, Prof Stephen Campbell states that "we know discharge from hospital can be a key patient safety issue and regulation needs reliable and attributable information. This research helps identify key areas for improvement especially the need for a unified understanding of the risk posed by discharge and information-sharing".