Culture

The value of diagnostic testing for SARS-CoV-2: When, whom, what and how often to test?

Washington, DC - March 27, 2020 - As we enter the second quarter of the COVID-19 pandemic, with testing for SARS-CoV-2 increasingly available (though still limited and slow in some areas), clinicians and public health officials are faced with new questions and challenges regarding testing for this novel virus. Since SARS-CoV-2 is a new virus, there is little evidence to fall back on for test utilization and diagnostic stewardship. New research published in mBio, an open-access journal of the American Society for Microbiology, addresses the potential uses of two main types of tests.

ASM convened a summit of coronavirus experts on Monday, March 23rd, who summarized the value and potential uses of two types of tests for SARS-CoV-2, nucleic acid amplification tests for viral RNA and antibody detection tests. The authors, including ASM CEO Stefano Bertuzzi and ASM President Robin Patel, also spoke at a press conference the following day and offered recommendations and limitations for both types of tests.

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American Society for Microbiology

German scientists identify microbe that could help degrade polyurethane-based plastics

There may be a small answer to one of the biggest problems on the planet.

German researchers report in the journal Frontiers in Microbiology that they have identified and characterized a strain of bacteria capable of degrading some of the chemical building blocks of polyurethane.

"The bacteria can use these compounds as a sole source of carbon, nitrogen and energy," said Dr. Hermann J. Heipieper, a senior scientist at the Helmholtz Centre for Environmental Research-UFZ in Leipzig, Germany and co-author of the new paper. "This finding represents an important step in being able to reuse hard-to-recycle PU products."

In 2015, polyurethane products alone accounted for 3.5 million tons of the plastics produced in Europe. Polyurethane is used in everything from refrigerators and buildings to footwear and furniture to numerous other applications that can leverage its lightweight, insulating and flexible properties.

Unfortunately, polyurethane is difficult and energy-intensive to recycle or destroy as most of these kinds of plastics are thermosetting polymers that do not melt when heated. The waste mostly ends up in landfills where it releases a number of toxic chemicals, some of which are carcinogenic.

The use of microorganisms like bacteria and fungi to break down oil-based plastics is an ongoing area of research. However, few studies have addressed biodegradation of polyurethanes like the current paper.

The team out of Germany managed to isolate a bacterium, Pseudomonas sp. TDA1, from a site rich in brittle plastic waste that shows promise in attacking some of the chemical bonds that make up polyurethane plastics.

The researchers performed a genomic analysis to identify the degradation pathways at work. They made preliminary discoveries about the factors that help the microbe metabolize certain chemical compounds in plastic for energy. They also conducted other analyses and experiments to understand the bacterium's capabilities.

This particular strain is part of a group of bacteria that are well-known for their tolerance of toxic organic compounds and other forms of stress, according to Dr. Christian Eberlein with the Helmholtz Centre for Environmental Research-UFZ. He is a co-author on the paper who coordinated and supervised the work.

"That trait is also named solvent-tolerance and is one form of extremophilic microorganisms," he said.

The research is part of a European Union scientific program dubbed P4SB (From Plastic waste to Plastic value using Pseudomonas putida Synthetic Biology), which is attempting to find useful microorganisms that can bioconvert oil-based plastics into fully biodegradable ones. As the name implies, the project has focused on a bacterium known as Pseudomonas putida.

In addition to polyurethane, the P4SB consortium, which includes the Helmholtz Centre for Environmental Research-UFZ, is also testing the efficacy of microbes to degrade plastics made of polyethylene terephthalate (PET), which is widely used in plastic water bottles.

Heipieper said that the first step of any future research on Pseudomonas sp. TDA1 will be to identify the genes that code for the extracellular enzymes that are capable of breaking down certain chemical compounds in polyester-based polyurethanes. Extracellular enzymes, also called exoenzymes, are proteins secreted outside of a cell that cause a biochemical reaction.

However, there is no immediate plan to engineer these or other enzymes using synthetic biology techniques for bioplastic production. That could involve, for instance, genetically converting the bacteria into mini-factories capable of transforming oil-based chemical compounds into biodegradable ones for planet-friendly plastics.

Heipieper said more "fundamental knowledge" like the one gathered in the current study is needed before scientists can make that technological and commercial leap.

One small step at a time.

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Frontiers

A new way to study HIV's impact on the brain

Though many negative repercussions of human immunodeficiency virus infection can be mitigated with the use of antiretroviral therapy (ART), one area where medical advances haven't made as much progress is in the reduction of cognitive impacts. Half of HIV patients have HIV-associated neurocognitive disorders (HAND), which can manifest in a variety of ways, from forgetfulness and confusion to behavior changes and motor deficiencies.

To better understand the mechanisms underlying HAND, researchers from Penn's School of Dental Medicine and Perelman School of Medicine and from the Children's Hospital of Philadelphia (CHOP) brought together their complementary expertise to create a laboratory model system using three of the types of brain cells thought to be involved. Led by doctoral student Sean Ryan, who was co-mentored by Kelly Jordan-Sciutto of Penn Dental Medicine and Stewart Anderson of CHOP and Penn Medicine, the model recapitulates important features of how HIV infection and ART affect the brain.

"Frankly the models we generally use in the HIV field have a lot of weaknesses," says Jordan-Sciutto, co-corresponding author on the paper, which appears in the journal Stem Cell Reports. "The power of this system is it allows us to look at the interaction between different cell types of human origin in a way that is more relevant to patients than other models."

In addition to studying HIV, members of the team plan to use the same model to shed light on the neurological mechanisms that underlie other conditions, such as schizophrenia, Alzheimer's, and even normal aging.

"We're collaborating with a variety of colleagues to use this system to study Alzheimer's disease as well as schizophrenia," says Anderson, co-corresponding author on the paper. "We have the components in a dish that we know are interacting in these diseases, and this gives us a new mix-and-match way to understand how certain cells are contributing to neuronal damage."

Indeed, the impetus to create the model grew not out of HIV research but work that Ryan was pursuing in Anderson's lab on schizophrenia.

"We had been looking at the role of microglia, the resident immune cells of the central nervous system," says Ryan, first author on the work. "We wanted to see if we could see the mechanistic changes that occur with microglia in schizophrenia."

To do so, Ryan and Anderson were interested in using human-induced pluripotent stem cells--adult cells that are reprogrammed to resemble embryonic stem cells--which can be coaxed into differentiating into a variety of different cell types.

But schizophrenia is a complicated disease with a variety of contributing genetic and environmental factors and a broad spectrum of presentations. Rather than looking at something complex, they sought to apply their new system to a disease that likewise causes neurological damage but does so in a more dramatic way and in which microglia are also implicated: HIV/AIDS infection.

They reached out to Jordan-Sciutto, who has deep experience investigating the mechanisms of HAND and was eager for the opportunity to develop a model superior to those currently available. Together, the scientists identified the three cell types they were most interested in studying: neurons, astrocytes, and microglia.

Neurons aren't directly infected by HIV but are known to be damaged during infection. Meanwhile astrocytes are believed to interact with neurons, causing damage by sending pro-inflammatory factors into the spaces between cells, called synapses. And microglia, which are responsible for maintaining a healthy environment in the absence of disease, are seen to expand and contribute to inflammation during HIV infection.

After nailing the technical challenge of creating this tractable model in which each cell type is generated independently and then mixed together, the team used it to probe how HIV infection and ART impact the cells, both alone and in combination.

"A lot of people are taking PreEP [pre-exposure prophylaxis] if they're in a situation where their risk of contracting HIV is heightened," says Ryan. "Just as we want to understand the cognitive impacts of HIV, we also want to see whether these drugs alone are impacting the brain health of otherwise healthy people."

The researchers looked at RNA expression in their cultures to get a sense of what proteins and signaling pathways were becoming activated in each scenario. During infection, they saw inflammatory pathways that had previously been implicated in HIV in earlier research. When they introduced the antiretroviral drug EFZ, which is not in common use in the United States but remains a frontline therapy in many other areas of the world, with an infection, the activity of most of these pathways was reduced.

"But this scenario involved its own unique response," says Ryan. Certain pathways associated with inflammation and damage remained despite the introduction of EFZ.

"EFZ treatment of the tri-cultures that included HIV-infected microglia reduces inflammation by around 70%," Ryan says. Interestingly, EFZ by itself also triggered inflammation, though to a lesser extent than infection.

"It seems a combination of infection and ART is creating its own unique response that is different from the sum of its parts," Ryan says. "Knowing what pathways are still active due to ART could help us appropriately target additional therapies so patients don't develop HAND."

Many features of infection seen in the three-cell culture mirror what is known from HIV infection and ART treatment in people, giving the researchers confidence in the reliability of their model.

"Just looking at the microglia," says Anderson, "we see in our system that they are taking on both of their normal roles in keeping key signaling systems balanced during their normal state and activating and causing damage when they're fighting infection. We're able to model normality and abnormality in a way we haven't been able to before."

For Jordan-Sciutto, the new system "is really going to change the way my lab operates going into the future." She's hopeful many other HIV scientists will take it up to further their studies as she also explores more aspects of HIV's impact on the brain, such as how it navigates through the blood-brain barrier that normally protects the central nervous system from inflammation and infection.

The study authors give credit to the collaborative environment at Penn for this cross-disciplinary project. "Tentacles of this project extend from CHOP to the dental school to the vet school to the medical school," says Anderson. "Penn is a very special place where people seem to be more likely to share their technologies around and let other people work with and develop them. This project is a great example of that."

Kelly L. Jordan-Sciutto is vice chair and professor in the Department of Basic and Translational Sciences in Penn's School of Dental Medicine, associate dean of graduate education, and director of biomedical graduate studies at the Perelman School of Medicine.

Credit: 
University of Pennsylvania

Double-walled nanotubes have electro-optical advantages

image: Rice University theorists have calculated flexoelectric effects in double-walled carbon nanotubes. The electrical potential (P) of atoms on either side of a graphene sheet (top) are identical, but not when the sheet is curved into a nanotube. Double-walled nanotubes (bottom) show unique effects as band gaps in inner and outer tubes are staggered.

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Yakobson Research Group/Rice University

HOUSTON - (March 27, 2020) - One nanotube could be great for electronics applications, but there's new evidence that two could be tops.

Rice University engineers already knew that size matters when using single-walled carbon nanotubes for their electrical properties. But until now, nobody had studied how electrons act when confronted with the Russian doll-like structure of multiwalled tubes.

The Rice lab of materials theorist Boris Yakobson has now calculated the impact of curvature of semiconducting double-wall carbon nanotubes on their flexoelectric voltage, a measure of electrical imbalance between the nanotube's inner and outer walls.

This affects how suitable nested nanotube pairs may be for nanoelectronics applications, especially photovoltaics.

The theoretical research by Yakobson's Brown School of Engineering group appears in the American Chemical Society journal Nano Letters.

In an 2002 study, Yakobson and his Rice colleagues had revealed how charge transfer, the difference between positive and negative poles that allows voltage to exist between one and the other, scales linearly to the curvature of the nanotube wall. The width of the tube dictates curvature, and the lab found that the thinner the nanotube (and thus larger the curvature), the greater the potential voltage.

When carbon atoms form flat graphene, the charge density of the atoms on either side of the plane are identical, Yakobson said. Curving the graphene sheet into a tube breaks that symmetry, changing the balance.

That creates a flexoelectric local dipole in the direction of, and proportional to, the curvature, according to the researchers, who noted that the flexoelectricity of 2D carbon "is a remarkable but also fairly subtle effect."

But more than one wall greatly complicates the balance, altering the distribution of electrons. In double-walled nanotubes, the curvature of the inner and outer tubes differ, giving each a distinct band gap. Additionally, the models showed the flexoelectric voltage of the outer wall shifts the band gap of the inner wall, creating a staggered band alignment in the nested system.

"The novelty is that the inserted tube, the 'baby' (inside) matryoshka has all of its quantum energy levels shifted because of the voltage created by exterior nanotube," Yakobson said. The interplay of different curvatures, he said, causes a straddling-to-staggered band gap transition that takes place at an estimated critical diameter of about 2.4 nanometers.

"This is a huge advantage for solar cells, essentially a prerequisite for separating positive and negative charges to create a current," Yakobson said. "When light is absorbed, an electron always jumps from the top of an occupied valence band (leaving a 'plus' hole behind) to the lowest state of empty conductance band.

"But in a staggered configuration they happen to be in different tubes, or layers," he said. "The 'plus' and 'minus' get separated between the tubes and can flow away by generating current in a circuit."

The team's calculations also showed that modifying the nanotubes' surfaces with either positive or negative atoms could create "substantial voltages of either sign" up to three volts. "Although functionalization could strongly perturb the electronic properties of nanotubes, it may be a very powerful way of inducing voltage for certain applications," the researchers wrote.

The team suggested its findings may apply to other types of nanotubes, including boron nitride and molybdenum disulfide, on their own or as hybrids with carbon nanotubes.

Credit: 
Rice University

Lessons from the Spanish flu: Early restrictions lowered disease, mortality rates

MAYWOOD, IL--Large events are cancelled, restaurants and non-essential businesses are closed, and in many states, residents have been asked to shelter in place, all to limit the spread and impact of the COVID-19 virus. But are strict and early isolation and other preventative mandates really effective in minimizing the spread and impact of a disease outbreak?

Stefan E. Pambuccian, MD, a Loyola Medicine cytologist, surgical pathologist and professor and vice chair of the Department of Pathology and Laboratory Medicine at Loyola University Chicago Stritch School of Medicine, has reviewed published data and research from three papers dating back to the 1918-19 Spanish flu pandemic, which infected one-fifth to one-third of the world's population and killed 50 million people.

According to the data and analysis, cities that adopted early, broad isolation and prevention measures--closing of schools and churches, banning of mass gatherings, mandated mask wearing, case isolation and disinfection/hygiene measures--had lower disease and mortality rates. These cities included San Francisco, St. Louis, Milwaukee and Kansas City, which collectively had 30% to 50% lower disease and mortality rates than cities that enacted fewer and later restrictions. One analysis showed that these cities also had greater delays in reaching peak mortality, and the duration of these measures correlated with a reduced total mortality burden.

"The stricter the isolation policies, the lower the mortality rate," says Dr. Pambuccian. He studied the Spanish flu, including prevention measures and outcomes, to help develop standards for staffing and safety in the cytology lab, where infectious diseases like the COVID-19 virus are diagnosed and studied at the cellular level. His broader article appeared online this week in the Journal of the American Society of Cytopathology.

Like today, not everyone in 1918 and 1919 thought the strict measures were appropriate or effective at the time.

An estimated 675,000 people died in the U.S. from the Spanish flu, "and there was skepticism that these policies were actually working," says Dr. Pambuccian. "But they obviously did make a difference."

In 1918, the world was still at war "with overcrowded barracks," and much of the U.S. lived with "poverty, poor nutrition, poor hygiene, household/community-level crowding, and a lack of preparation of the population and decision makers due to cognitive inertia and poor medical and insufficient nursing care," says Dr. Pambuccian.

"Although the world is a much different place than it was 100 years ago, the efficacy of the measures instituted during the 1918-19 pandemic gives us hope that the current measures will also limit the impact of the COVID-19 pandemic."

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Loyola Medicine

Copper boosts pig growth, and now we know why

image: Research from the University of Illinois explains why copper enhances feed conversion rates in pigs.

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University of Illinois College of Agricultural, Consumer and Environmental Sciences

URBANA, Ill. - Pigs have better feed conversion rates with copper in their diets, but until now, scientists didn't fully understand why. Existing research from the University of Illinois shows copper doesn't change fat and energy absorption from the diet. Instead, according to new research, the element seems to enhance pigs' ability to utilize fat after absorption, resulting in increased energy utilization of the entire diet.

"Our results indicate copper hydroxychloride is enhancing metabolism of fat, and that's how the pigs get more energy. And that, we believe, can explain why pigs have better feed conversion rates when we feed this copper source in the diets," says Hans H. Stein, professor in the Department of Animal Sciences at Illinois and co-author of a new study in the Journal of Animal Science.

In the study, Stein and his collaborators fed pigs one of two diets. Both primarily contained corn, soybean meal, and distillers dried grains with solubles, but one diet (a control) contained only 20 milligrams of copper chloride per kilogram. The experimental diet was identical, except it also contained 150 milligrams of copper hydroxychloride per kilogram.

Pigs consuming the experimental diet experienced greater average daily gain and gain-to-feed ratio, representing better feed conversion and economic savings for producers.

Stein's previous work showed fat and energy digestibility didn't change with inclusion of similar rates of copper hydroxychloride. So, to really understand copper's effects on post-absorptive fat metabolism, the researchers evaluated gene expression in tissue samples from the pigs.

"We saw greater expression of genes involved in lipid metabolism and lipid utilization in the liver, adipose tissue, and to a lesser degree in the muscle," Stein says. "This indicates that dietary copper may affect signaling pathways associated with lipid metabolism by improving the uptake, transport, and utilization of fatty acids."

Copper's ability to boost feed conversion rates is welcome news with agencies regulating antibiotics as growth promoters.

But copper isn't necessarily a perfect workaround.

In Europe, Stein says, environmental concerns prompt copper regulation in waste streams. That's why understanding copper's role in pig nutrition is so important. If less copper or a different form with a smaller environmental footprint could fulfill the same biological function, producers could continue to benefit while also protecting the environment.

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University of Illinois College of Agricultural, Consumer and Environmental Sciences

COVID-19 alert: Heart and kidney patients should keep taking their medicines

As the COVID-19 pandemic unfolds, inaccurate medical information has flooded social media and other channels. One potentially lethal example is that patients who take renin-angiotensin system (RAS) blockers, particularly angiotensin II type 1 receptor blockers (ARBs), may be more susceptible to the virus.

However, in an article published in the American Heart Association journal Hypertension, Murray Epstein, M.D., emeritus professor of medicine at the University of Miami Miller School of Medicine, and colleagues warn there is little credible or consistent evidence to back up this concern. Equally important, foregoing these important medications would dramatically increase health risks for hundreds of millions of patients with hypertension, congestive heart failure, and chronic kidney disease.

"The only thing we can conclude definitively, based on all the known data, is that there is no credible evidence whatsoever that ARBs enhance susceptibility to COVID," said Dr. Epstein, who edits the only medical textbook that focuses exclusively on ARBs.*

In the article "Renin-angiotensin system (RAS) blockers and the COVID-19 pandemic: at present there is no evidence to abandon RAS blockers," Dr. Epstein and coauthors Jan Danser, Ph.D., of Erasmus Medical Center in Rotterdam, and Daniel Batlle, M.D., at Northwestern University, carefully reviewed the available data to determine whether ARBs pose any significant risk.

They note the concern originated from reports that the angiotensin-converting enzyme 2 (ACE 2) protein receptor may enable viral entry into cells. Amplified by various media, this led some patients to discontinue their medications - either on their own or based on advice from a physician.

However, the evidence that ARBs may increase COVID-19 risk is inconsistent, at best. Though some studies have shown ARBs increase ACE 2 activity in animal models, it must be emphasized that the results have been inconsistent.

"People are making an unadvised leap," said Dr. Epstein. "The logic goes that, if it enhances penetrability, it enhances susceptibility to the disease, but that's a dangerous conclusion. What investigators have found varies widely, depending on the organ studied, the experimental animal model and the ARB being used in the study. In summary, there is a complete lack of consistency."

While these is no credible evidence that ARBs increase COVID-19 risk, Dr. Epstein notes there are clear dangers for patients who stop taking their medications. ARBs are prescribed for high blood pressure, congestive heart failure, kidney disease and other conditions. Widespread discontinuation of ARBs and ACE inhibitors could cause destabilization of blood pressure control and decompensation of heart failure patients, leading to sharp increases in heart attacks and strokes and a worsening of kidney failure.

"This would be a double tragedy, because it would be happening precisely at a time when our hospital and ICU resources are stressed to the limit," said Dr. Epstein. "It will further tax our medical facilities and hospitals, and it will be truly tragic."

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University of Miami Miller School of Medicine

A lifesaving reason to have more women on boards: ensuring consumer safety

In a study published online yesterday focused on the medical products industry - which includes medical devices, pharmaceuticals and biologics - a group of researchers found that, compared to firms with all-male boards, firms with female directors announced high-severity product recalls 28 days sooner. This is a 35% reduction in the time between when a firm was first made aware of the defect and when the firm decided to recall the defective product.

The study, from faculty at Lehigh University, University of Notre Dame, Indiana University and Auburn University, is the first to examine the impact of female board representation on operations management, specifically in product recall decision-making. It was published in Manufacturing and Service Operations Management.

According to co-author Corinne Post, a professor of management at Lehigh University, the U.S. Food and Drug Administration (FDA) classifies recalls into three categories of severity: class 1 (high severity), class 2 (moderate severity), and class 3 (low severity). A class 1, high-severity recall is one where the product defects are the most serious, even life-threatening. "For the types of recalls classified as high-severity, how quickly they are recalled can truly be a matter of life or death," says Post.

The researchers found that the number of women on boards also had an impact on the high-severity recall outcomes. When boards had just one female director, seriously defective products were not recalled more quickly than with all-male boards. It was only when there were at least two female directors on the board that the timeliness of severe product recalls increased.

"When there were three female directors, the recall decision moved along even faster," adds Post.

The authors write that low-severity, or "...class 3 recalls, which are associated with nonharmful issues such as labeling or packaging nonconformities, have significant discretion in whether or not they are ever initiated by firms and represent an ideal context to examine how changes in board gender composition influences the firm's tendency to either take accountability for, or overlook, product quality problems that contain significant initiation discretion."

The researchers report that for low severity recalls, for which executives have much greater discretion than high-severity ones, boards with female directors announced 120% more recalls, compared to boards that had no female directors. That is equivalent to 12 additional recalls per firm.

"In this case, the addition of just one female director caused a change in how these decisions were made," says Post. "The number of recalls of this type announced continue to increase as firms add each additional female director."

The team notes that more research is needed to determine why the presence of women on boards is associated with such different product recall decisions. Though they assert that underlying the link between board composition and product recalls is an understanding that boards are established specifically to set the tone for how managers make critical firm decisions.

"We hypothesize that boards with more women might set a tone for stricter abidance by FDA rules and may also have higher aversion to risk when it comes to possible product harm," says Post. "Boards that include women may also be more responsive to a diverse set of stakeholders, including at-risk customers."

The study entitled, "The Influence of Female Directors on Product Recall Decisions," was published online today in Manufacturing and Service Operations Management. (Co-authors: Kaitlin D. Wowak, University of Notre Dame; George P. Ball, Indiana University; and, David J. Ketchen Jr., Auburn University.)

A tale of two product recall approaches

To arrive at their results, Post and her colleagues analyzed data obtained through a Freedom of Information Act (FOIA) request, as well as recall timing data provided by a senior FDA leader. In total, they analyzed 4,271 medical product recalls from 2002 to 2013 across 92 FDA-regulated, publicly traded firms. In addition to their empirical research, the team interviewed two managers: a VP of quality and a director of manufacturing, at two FDA-regulated Fortune 500 medical product firms?both involved with monitoring quality issues. When a product quality issue arises, usually a recall committee is formed. Committee findings are shared with the board, which provides feedback.

"In other words," the authors write, "boards do not make the recall decisions, but instead they set the tone and expectations for how managers are to make these decisions."

The paper provides a glimpse into how the process unfolds at one firm, where the default position is to recall in the absence of compelling reasons not to: "The VP of quality mentioned that at her firm, the recall decision focuses keenly on customer harm and that managerial recall committees are only allowed three days to prove that a recall is not warranted once a product quality issue comes to their attention. If unable to do so in three days, a recall is initiated. The default at this firm is to recall and to do so quickly. This expectation for quick and deliberate action prioritizing customer safety was established by the firm's board. In fact, it is the female directors on the board at this firm who are particularly concerned with customer safety."

By contrast, the researchers write that the manufacturing director they spoke with indicated that at his firm the default position is to err toward inaction unless the committee finds evidence that makes a recall the only viable option:

"There, managerial recall committees have the burden of proving that a recall is absolutely necessary and if unable to do so, no recall is initiated. Recall committees can take as long as they deem appropriate and the deliberations center on cost-benefit analyses more than customer safety. This cost-benefit prioritization is driven by the board. In this firm, the male directors often inquire about who is going to be fired and how quickly they will be fired following a recall announcement."

A call to action for greater board diversity

"Our data analysis combined with the information gleaned from our interviews, show that there is a difference in very real and important consumer safety outcomes between firms who have added more women to their boards and those who have not," says Post.

CEOs and ESG (environmental, social and governance) analysts may be especially interested in these results, adds Post, as they seek to understand how board diversity might correlate with socially responsible corporate decision-making.

"My colleagues and I join with recent calls for all directors and all boards to look beyond the bottom-line," says Post. "Being responsive to their firm's stakeholders, especially when defects in their products may harm or kill, is not only good business but could save lives."

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Lehigh University

Triple-threat genetic toolkit aids with eco-friendly chemical production

image: University of Illinois at Urbana-Champaign Department of Chemical and Biomolecular Engineering scientists (from left) William L. Lyon, Mingfeng Cao, Zia Fatma, and Huimin Zhao developed genetic tools to produce valuable bioproducts from low pH-tolerant yeast strain.

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Center for Advanced Bioenergy and Biofuels Innovation (CABBI)

Researchers have developed a triad of innovative tools to engineer low-pH-tolerant yeast Issatchenkia orientalis for production of valuable bioproducts from renewable biomass.

A paper published in Metabolic Engineering outlines the study's three-pronged approach and its importance to the field of sustainable chemical production.

The team was led by Mingfeng Cao, a Research Scientist in the University of Illinois at Urbana-Champaign's Department of Chemical and Biomolecular Engineering (ChBE). Cao works in ChBE Professor Huimin Zhao's lab at the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy-funded Bioenergy Research Center (BRC). CABBI Postdoctoral Researcher Zia Fatma, also in Zhao's lab, is a coauthor of the study.

In an effort to decrease dependence on nonrenewable fossil fuels, scientists are exploring methods of producing valuable products from renewable biomass using organisms such as yeast. Generating economically competitive quantities of these products involves metabolic engineering -- editing cells' genetic blueprint to produce greater quantities of desired substances.

Scientists previously engineered the conventional yeast Saccharomyces cerevisiae in this manner. A commonly used production host, S. cerevisiae's conduciveness to genetic manipulation makes it a prime candidate for metabolic engineering.

"In addition to conventional yeasts, we're discovering that nonconventional yeasts can prove to be just as high-performing," Cao said. "The more organisms we can engineer for valuable compound production, the more opportunities we will have in order to make chemical production economically and environmentally sustainable."

The study by Cao and Zhao focuses on the yeast strain I. orientalis, notable for its ability to thrive in low-pH environments. Scientists believe that this tolerance for extreme acidity positions I. orientalis as a robust organic acid producer.

Until now, the viability of I. orientalis for chemical production has remained less explored due to a shortage of genetic manipulation strategies. CABBI scientists remedied this knowledge gap by inventing three key tools.

Previously, the research team had identified a genetic tool involving plasmids, DNA molecules necessary for genetic manipulation and reproduction. To edit an organism's genome, plasmids must be able to replicate stably. The team proved that an autonomously replicating DNA sequence (ARS) from Saccharomyces cerevisiae can be used to stabilize plasmid replication in I. orientalis, but only to an extent; on its own, the addition is insufficient.

Achieving stability and making I. orientalis receptive to CRISPR/CAS9 gene editing systems requires that the ARS is augmented with a functional centromere (CEN), the portion of a DNA sequence responsible for stabilizing cell division. The first novel genetic tool identified in this study is a functional CEN sequence in the I. orientalis genome. Because a CEN-ARS pairing is necessary for stable plasmid division, this discovery facilitates genetic engineering of I. orientalis for high-value, high-quantity compound production.

In addition to isolating a CEN sequence in I. orientalis, the research team identified constitutive promoters and terminators (components of a DNA strand that influence the way in which genes are expressed).

Finely tuned genetic expression -- directly resulting from terminator and promoter behavior -- is key to optimizing an organism for chemical production. By characterizing strong terminators and promoters in I. orientalis, researchers can engineer the particular expressions necessary to produce chemicals at high levels.

The third tool CABBI researchers developed is a fast and efficient in vivo (meaning "within a living organism") DNA assembly method to construct a biochemical pathway in I. orientalis.

For processes in I. orientalis to be high-yielding and economically viable, cellular pathways -- chains of actions and reactions within a cell that cause a desired product or response -- must often be engineered.

Taking a xylose utilization pathway originally designed for S. cerevisiae as an example, the research team used an in vivo DNA assembly method to introduce one such synthetic pathway in I. orientalis. As a result, I. orientalis could use xylose as a sole carbon source.

Though not fully optimized, this example demonstrated that a more sophisticated in vivo assembly method can be adopted for efficient construction of reliable biosynthetic pathways within I. orientalis, ultimately driving toward valuable compound production.

In conclusion, this study generated a robust set of three novel genetic tools to facilitate increased expression of target genes and aid in manufacturing of bioproducts such as organic acids from the yeast I. orientalis.

Credit: 
University of Illinois at Urbana-Champaign Institute for Sustainability, Energy, and Environment

A plant-based diet helps to prevent and manage asthma, according to new review

WASHINGTON--A plant-based diet can help prevent and manage asthma, while dairy products and high-fat foods raise the risk, according to a new review published in Nutrition Reviews.

Asthma is a common chronic condition in which the airways become narrow and inflamed--sometimes leading to difficulty with breathing, coughing, wheezing, and shortness of breath.

"Asthma is a condition that affects more than 25 million Americans, and unfortunately it can make people more vulnerable in the COVID-19 outbreak," says study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee. "This research offers hope that dietary changes could be helpful."

Researchers with the Physicians Committee for Responsible Medicine examined the evidence related to diet and asthma and found that certain foods--including fruits, vegetables, whole grains, and other high-fiber foods--can be beneficial, while others--such as dairy products and foods high in saturated fat--can be harmful.

The review authors highlight a study finding that when compared to a control group, asthma patients who consumed a plant-based diet for eight weeks experienced a greater reduction in use of asthma medication and less severe, less frequent symptoms. In another study, asthma patients adopted a plant-based diet for a year and saw improvements in vital capacity--a measure of the volume of air patients can expel--and other measures.

The authors suggest that a plant-based diet is beneficial because it has been shown to reduce systemic inflammation, which can exacerbate asthma. Plant-based diets are also high in fiber, which has been positively associated with improvements in lung function. The researchers also highlight the antioxidants and flavonoids found in plant foods, which may have a protective effect.

The review also finds that dairy consumption can raise the risk for asthma and worsen symptoms. One 2015 study found that children who consumed the most dairy had higher odds of developing asthma, compared with the children consuming the least. In another study, children with asthma were placed in either a control group, where they made no dietary changes, or in an experimental group where they eliminated dairy and eggs for eight weeks. After eliminating dairy, the experimental group experienced a 22% improvement in peak expiratory flow rate--a measure of how fast the children were able to exhale--while children in the control group experienced a 0.6% decrease.

High fat intake, consumption of saturated fat, and low fiber intake were also associated with airway inflammation and worsened lung function in asthma patients.

"This groundbreaking research shows that filling our plates with plant-based foods--and avoiding dairy products and other high-fat foods--can be a powerful tool for preventing and managing asthma," says Dr. Kahleova.

During the COVID-19 pandemic, the Centers for Disease Control and Prevention urges those with asthma to have a plan in place--including stocking up on supplies, taking asthma medication as needed, avoiding crowds, and practicing good hygiene.

Credit: 
Physicians Committee for Responsible Medicine

UK local authorities not ready for the number of deaths from Covid-19

image: UK local authorities not ready for the number of deaths from Covid-19, according to new research
The situation could lead to a bottleneck in burials and cremations, mortuaries filled beyond capacity and the possibility of mass graves.

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University of Huddersfield

UNIVERSITY of Huddersfield experts have made stark warnings about the impact of coronavirus on local authorities. A major increase in mortality rates and staff absences will mean a struggle to issue death certificates, leading to a bottleneck in burials and cremations, with mortuaries filled beyond capacity.

Even if fatality rates are at the lower end of expectations - one percent of virus victims - it is highly likely that death and bereavement services will be overwhelmed, according to newly-published research by Dr Julia Meaton, Dr Anna Williams and researcher Helen-Marie Kruger.

They have drawn on a wide range of data that includes the experience of previous pandemics and analysed the readiness of a local authority in England - anonymised in the article - in order to appraise the scale of the challenge.

The article is titled Pandemic Continuity Planning; will coronavirus test local authority business plans? and is published by the online journal Emergency Management Review.

The findings are based on research carried out in 2019, examining the potential impact of a flu pandemic, but the authors have updated and adapted their facts and figures so that conclusions and recommendations are of immediate relevance. They provide tables and figures that were up-to-date at the point of publication.

"The personal tragedy and loss will be unquantifiable," write the University trio, adding however that the focus of their paper is on how authorities will manage excess deaths. For example, burial and cremation services could be beyond capacity four or five weeks into the outbreak.

Limited cemetery and body storage space will also be a major problem, with mass graves a possibility, although this would be highly controversial and would upset and anger many communities, state the authors.

They have examined the role of coroners and analysed the continuity plans drawn up by local authorities in the event of a pandemic, finding a number of flaws.

In making recommendations, the authors state that both registration and bereavement services know the death toll will increase during a pandemic but are unsure of the actual figures to plan for.

"Underestimating the mortality rate could reduce the effectiveness of business continuity plans, whereas knowing what to expect will focus attention on the resources required. An option would be to have an escalating business continuity plan, where the service prepares for a worst-case scenario, which can then be scaled back depending on the anticipated mortality rate."

Recommendations include the possibility of ring-fencing employees so that during periods of severe staff shortfalls their availability will be guaranteed.

Technological innovations could include an online death registration service that would speed up the process, although with insufficient safeguards it could be open to misuse.

The authors conclude: "The focus has been on the operational implications for a local authority service but the issues this paper raises are primarily about people and how we, as a society, treat our citizens in life and in death. In a pandemic situation, there is likely to be a necessary change to the 'business as usual' death and bereavement management services. How humanely these are managed is hugely important for those affected at the time of crisis and the humanity of the government's response will reflect the nature and values of our society, and will be judged accordingly".

Credit: 
University of Huddersfield

Cardiovascular implications of fatal outcomes of patients with COVID-19

What The Study Did: Evaluating the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).

Authors: Zhibing Lu, M.D., and Xinghuan Wang, M.D., of  Zhongnan Hospital of Wuhan University in China, are the corresponding authors.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamacardio.2020.1017)

Editor's Note: The article includes funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Cardiac involvement in a patient with COVID-19

What The Study Did: A description of the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms.

Authors: Marco Metra, M.D., of the Institute of Cardiology in Brescia, Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamacardio.2020.1096)

Editor's Note: The article includes conflict of interest disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Potential effects of coronaviruses on the cardiovascular system

What The Study Did: An overview of the basics of coronaviruses, with a focus on coronavirus disease 2019 (COVID-19) along with their effects on the cardiovascular system.

Authors: Mohammad Madjid, M.D., M.S., of the University of Texas Health Science Center at Houston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamacardio.2020.1286)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Credit: 
JAMA Network

Why does your cotton towel get stiff after natural drying?

image: A cotton bundle after natural drying became stiff as if glued (left), whereas the one dried by forced drainage in a washing machine together with physical agitation such as shaking remained flexible (right). (J. Surfact Deterg (2016), 19, 183)

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J. Surfact Deterg (2016), 19, 183

The remaining "bound water" on cotton surfaces cross-link single fibers of cotton, causing hardening after natural drying, according to a new study conducted by Kao Corporation and Hokkaido University. This provides new insight into unique water behaviors on material surfaces and helps us develop better cleaning technologies.

Cotton towels often become stiff when washed without fabric softener and naturally dried, but the mechanism behind it has remained a mystery. In previous studies, the research groups at Kao Corporation suggested the involvement of bound water -- a special type of water that exhibits unique properties on the surface of materials -- for the hardening. The group proposed a theoretical model in which the bound water that remains on the surface of cotton causes cross-linking between single fibers through a process called capillary adhesion.

In the current study published in The Journal of Physical Chemistry C, the research group reports direct observations of the bound water on cotton surfaces, providing strong evidence for Kao's model. Joined by Ken-ichiro Murata of Hokkaido University, the group employed special analytical techniques called atomic force microscopy (AFM) and AFM-based infrared spectroscopy (AFM-IR) to investigate the bound water on cotton surfaces at the molecular level.

The AFM observations indicated the existence of a viscous substance on the cotton surface that is not cellulose, the major component of cotton. This strongly suggested viscous bound water is present there causing capillary adhesion -- a phenomenon in which liquid sandwiched between solid surfaces causes adhesion of them. In the following experiments, the AFM-IR spectra of naturally dried cotton surfaces showed two-peaks that indicate the existence of water. On the other hand, no peaks were observed after completely removing water on the cotton surface. Furthermore, the spectra, showing two clear peaks, suggested that the bound water takes two different states at the air-water interface and the water-cotton interface, respectively.

"The experiments clarified that bound water is evident on cotton surfaces and contributes to certain dynamic properties such as stiffness mediated by capillary adhesion. Also, the bound water itself manifested a unique hydrogen bonding state different from that of ordinary water," said Ken-ichiro Murata of Hokkaido University. Takako Igarashi of Kao Corporation added, "It has been thought that fabric softeners reduce friction between cotton fibers. However, our results showing the involvement of bound water in the hardening of cotton provide new insight into how fabric softeners work and can help us develop better agents, formulations and systems."

Credit: 
Hokkaido University