Culture

Readability of public health information on COVID-19 from governments, international agencies

What The Study Did: The readability of information about COVID-19 was evaluated on websites of public health agencies and governments of 15 countries.

Authors: Joseph P. Dexter, Ph.D., of Dartmouth College in Hanover, New Hampshire, 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/jamanetworkopen.2020.18033)

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

Credit: 
JAMA Network

Assessing SARS-CoV-2 transmission on an international flight

What The Study Did: This case series describes SARS-CoV-2 transmission on an international commercial airline flight and among a tourist group.

Authors: Sandra Ciesek, M.D., of Goethe University Frankfurt am Main, Germany, 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/jamanetworkopen.2020.18044)

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

Credit: 
JAMA Network

100 cool worlds found near the sun

image: Artist's impression of one of this study's superlative discoveries, the oldest known wide-separation white dwarf plus cold brown dwarf pair. The small white orb represents the white dwarf (the remnant of a long-dead Sun-like star), while the brown/orange foreground object is the newly discovered brown dwarf companion. This faint brown dwarf was previously overlooked until it was spotted by citizen scientists because it lies right within the plane of the Milky Way.

Image: 
NOIRLab/NSF/AURA/P. Marenfeld; acknowledgement: William Pendrill

Maunakea, Hawaii - How complete is our census of the Sun's closest neighbors? Astronomers and a team of data-sleuthing volunteers participating in Backyard Worlds: Planet 9, a citizen science project, have discovered roughly 100 cool worlds near the Sun - objects more massive than planets but lighter than stars, known as brown dwarfs.

With the help of W. M. Keck Observatory on Maunakea in Hawaii, the research team found several of these newly discovered worlds are among the very coolest known, with a few approaching the temperature of Earth -- cool enough to harbor water clouds.

The study will be published in the August 20, 2020 issue of the Astrophysical Journal and is available in preprint format on arXiv.org.

Discovering and characterizing astronomical objects near the Sun is fundamental to our understanding of our place in, and the history of, the universe. Yet astronomers are still unearthing new residents of the solar neighborhood. The new Backyard Worlds discovery bridges a previously empty gap in the range of low-temperature brown dwarfs, identifying a long-sought missing link within the brown dwarf population.

"These cool worlds offer the opportunity for new insights into the formation and atmospheres of planets beyond the solar system," said lead author Aaron Meisner from the National Science Foundation's NOIRLab. "This collection of cool brown dwarfs also allows us to accurately estimate the number of free-floating worlds roaming interstellar space near the Sun.

To identify several of the faintest and coolest of the newly discovered brown dwarfs, UC San Diego's Professor of Physics Adam Burgasser and researchers from the Cool Star Lab used Keck Observatory's sensitive Near-Infrared Echellette Spectrometer, or NIRES, instrument.

"We used the NIRES spectra to measure the temperature and gases present in their atmospheres. Each spectrum is essentially a fingerprint that allows us to distinguish a cool brown dwarf from other kinds of stars," said Burgasser, a co-author of the study.

Follow-up observations using NASA's Spitzer Space Telescope, Mont Megantic Observatory, and Las Campanas Observatory also contributed to the brown dwarf temperature estimates.

Brown dwarfs lie somewhere between the most massive planets and the smallest stars. Lacking the mass needed to sustain nuclear reactions in their core, brown dwarfs are sometimes referred to as "failed stars." Their low mass, low temperature, and lack of internal nuclear reactions make them extremely faint -- and therefore extremely difficult to detect. Because of this, when searching for the very coolest brown dwarfs, astronomers can only hope to detect such objects relatively close to the Sun.

To help find our Sun's coldest, nearest neighbors, astronomers with the Backyard Worlds project turned to a worldwide network of more than 100,000 citizen scientists. These volunteers diligently inspect trillions of pixels of telescope images to identify the subtle movements of nearby brown dwarfs and planets. Despite the advances of machine learning and supercomputers, there's still no substitute for the human eye when it comes to finding faint, moving objects.

Backyard Worlds volunteers have already discovered more than 1,500 stars and brown dwarfs near the Sun; this new discovery represents about 100 of the coldest in that sample. Meisner says this is a record for any citizen science program, and 20 of the citizen scientists are listed as co-authors of the study.

The availability of decades of astronomical catalogs through NOIRLab's Astro Data Lab helped make the discoveries possible.

"The technical burden of downloading billion-object astronomical catalogs is typically insurmountable for individual investigators - including most professional astronomers," said Meisner. "Thankfully, the Astro Data Lab's open and accessible web portal allowed Backyard Worlds citizen scientists to easily query massive catalogs for brown dwarf candidates."

Data sets from NASA's WISE satellite as well as archival observations from telescopes at Cerro Tololo Inter-American Observatory and Kitt Peak National Observatory were also key to these brown dwarf discoveries.

"It's exciting these could be spotted first by a citizen scientist," said Meisner. "The Backyard Worlds discoveries show that members of the public can play an important role in reshaping our scientific understanding of our solar neighborhood."

Credit: 
W. M. Keck Observatory

Federal and state websites flunk COVID-19 reading-level review

image: Info written at a higher grade level than recommended can place greater demands on the reader and cause people to miss key public health information.

Image: 
Richard Clark/Dartmouth College

HANOVER, N.H. - August 18, 2020 - Information about COVID-19 offered by the U.S. Centers for Disease Control and Prevention, the White House, and state health departments failed to meet recommendations for communicating with the public, according to a Dartmouth study.

The review of written web content during the onset of COVID-19 demonstrates that official information about the virus might have been too complex for a general audience. On average, government sources communicated about three grades higher than the reading level recommended by existing guidelines for clear communication.

The research, which also analyzed international health web pages, appears as a research letter in JAMA Network Open, a medical journal published by the American Medical Association.

"How public health information is presented can influence understanding of medical recommendations," said Joseph Dexter, a fellow at Dartmouth's Neukom Institute for Computational Science and senior author on the study. "During a pandemic it is vital that potentially lifesaving guidance be accessible to all audiences."

The U.S. Plain Writing Act of 2010 requires that "federal agencies use clear government communication that the public can understand and use." The CDC, the American Medical Association and the National Institutes of Health all recommend that medical information for the public should be written at no higher than an eighth-grade reading level.

After studying 137 web pages from federal and state sources, the team found that communications about COVID-19 averaged just over an 11th-grade reading level.

According to the study, information shared by the CDC and other U.S. sources during the onset of COVID-19 exceeded recommendations on the number of words in a sentence, word size, and the use of difficult terms related to public health.

Even though states are not required to follow the federal regulations, they might still benefit from complying with the guidelines. All 50 U.S. states provided information above the eighth-grade level. Nine of the 10 states with the highest illiteracy rates had websites written above a 10th-grade level.

Previous research has found that only 12 percent of American adults exhibit proficient health literacy.

"The differences between eighth-grade and 11th-grade reading levels are crucial. Text written at a higher grade level can place greater demands on the reader and cause people to miss key information," said Dexter.

According to the study, exceeding readability standards may have a greater effect on vulnerable communities with lower health literacy, potentially worsening the impacts of the pandemic.

"Information about COVID-19 can be complex, contradictory, and sometimes false. It is important that members of the public be able to use public health recommendations from trustworthy sources and not have to turn to less reliable outlets," said Dexter.

To assess the readability of information related to COVID-19, the research team analyzed web sites during the critical beginning stages of the pandemic in early April. Pages consulted were meant for general audiences and included lists of frequently asked questions and fact sheets.

Beyond the U.S., the study reviewed 18 international websites, including three public health agencies and 15 official government sites.

Almost all of the international pages scored above the eighth-grade level by five different assessments. All of the pages, including those from the World Health Organization, exceeded the U.S. national eighth-grade guideline by at least one measure.

"WHO coordinates a major effort to redirect anyone searching for information about COVID-19 to reliable sources," said Vishala Mishra, a co-author of the paper and a researcher at Madras Medical College. "Therefore, it becomes especially relevant for governments and health agencies, such as WHO and CDC, to provide more accessible health information that matches the public's health literacy."

Web pages containing COVID-19 information were judged using standard readability formulas that estimate text difficulty based on features such as word and sentence length. The reading level predictions of these formulas were assessed against health literacy guidelines based on federal regulations.

Credit: 
Dartmouth College

Smartphones are lowering student's grades, study finds

The ease of finding information on the internet is hurting students' long-term retention and resulting in lower grades on exams, according to a Rutgers University-New Brunswick study.

The study, published in the journal Educational Psychology, found that smartphones seem to be the culprit. Students who received higher homework but lower exam scores -- a half to a full letter grade lower on exams -- were more likely to get their homework answers from the internet or another source rather than coming up with the answer themselves.

"When a student does homework by looking up the answers, they usually find the correct answer, resulting in a high score on the assignment," said lead author Arnold Glass, a professor of psychology at Rutgers-New Brunswick's School of Arts and Sciences. "However, when students do that, they rapidly forget both the question and answer. Consequently, they transform homework from what has been, until now, a useful exercise into a meaningless ritual that does not help in preparing for exams."

The research also found that while 14 percent of students scored lower on exams than homework in 2008, that number jumped to 55 percent in 2017 as the use of smartphones for homework has become more common.

Glass says when students read a homework question, they should think about it, generate the answer on their own and commit to that answer.

"If the student does this first and then finds the correct answer online, the student is likely to remember the answer, which will have a significant long-term effect on subsequent exam performance," said Glass, whose goal was to determine when a student knows a particular fact, whether they remember it and can generalize it.

The study included 2,433 Rutgers-New Brunswick students in 11 different lecture courses. Over the 11-year period more than 232 different questions were created.

Working with co-author and graduate student Mengxue Kang, Glass and Kang's study is a part of an ongoing project to use technology to monitor academic performance and to assess the effects of new instructional technologies, like smartphones and the Internet, on how students perform in school.

Credit: 
Rutgers University

Evolution in real-time: How bacteria adapt to their hosts

image: Parachlamydia are widespread in the environment where they live in amoebae. The bacteria serve as a model system for studying the evolution of infectivity. The image shows two amoeba cells in pink that are infected with Parachlamydia (yellow/blue).

Image: 
© Patrick Arthofer

In the environment, they are often found inside unicellular organisms. A research team led by Matthias Horn at the Centre for Microbiology and Environmental Systems Science at the University of Vienna has made use of laboratory experiments to gain a better understanding of how these bacteria adapt to their host cell over time. This is due to changes in the genome and in gene expression. The study has been published in PNAS.

In the laboratory of the Center for Microbiology and Environmental Systems Science at the University of Vienna, so-called "Parachlamydia" was observed after a period of 14 months of evolution inside its unicellular host. Parachlamydia is a genus of environmental chlamydiae that is found in water or soil. In contrast to their human-pathogenic relatives, they are not infectious for humans. They live in unicellular organisms and are dependent on nutrients from their hosts. Therefore, over the course of time they have perfected mechanisms to invade host cells and reproduce inside them.

Theoretical predictions confirmed in the laboratory

Parachlamydia serves as a model system to study the adaptation of host-dependent bacteria in the laboratory. The evolutionary experiment carried out for this purpose involved over 500 generations of bacteria, which corresponds to a period of about 15,000 years in human time-frame.

To verify theoretical predictions on the development of infectivity, the bacteria were kept in the laboratory under two different experimental conditions. In one part of the experiment, the bacteria were dependent on frequent infection of new host cells in order to survive. In the other part, they were able to multiply permanently within one and the same host cell. "Our results reveal that if the bacteria are able to remain within one host cell and ensure that they continue to live in the daughter cells of the host when the host cell divides, their infectivity does not change. However, bacteria become increasingly infectious when they have to move from one host cell to another host cell in order to survive." explains Paul Herrera, first author of the study.

Adaptation of the bacteria at the molecular level

The researchers went one step further in their experiments. They examined the genes of the bacteria at the beginning of the evolutionary process and compared them with the genes after 500 generations of evolution. They found that the genes of the two groups of bacteria differed significantly at 1,161 sites.

However, this genetic information alone was not sufficient to explain the differences in infectivity. Only the subsequent analysis of gene expression - i.e. the use of the almost 2,500 genes during infection - revealed that the infectious bacteria, which have to switch between host cells, showed changes in the expression of genes crucial for the infection mechanism and for certain metabolic pathways that are important for survival outside the host cells.

"The transmission pathway plays a crucial role in the development of infectivity in host-dependent bacteria. The observed increase in infectivity is based on a variety of genetic differences and major changes in gene expression. These modifications result in the host cells becoming more easily infected and give the bacteria a better chance to survive outside the host cell," summarises Matthias Horn.

Credit: 
University of Vienna

Huddersfield research predicted anti-COVID steroid benefits

image: Huddersfield researchers publish study that found that dexamethasone could reduce death rates in hospitalised COVID-19 patients early in the pandemic.

Image: 
University of Huddersfield

A study from early in the global coronavirus pandemic that evidenced the benefits of using steroids to combat COVID-19 in severely ill patients could have saved lives, according to the University of Huddersfield researchers involved.

Dr Hamid Merchant and Dr Syed Shahzad Hasan assessed the results of using corticosteroid such as dexamethasone on hospitalised COVID-19 patients with acute respiratory distress syndrome (ARDS) on respiratory support. By mid-April they had found that the proportion of COVID-19 patients who died in the steroid group was significantly lower compared to those who did not receive corticosteroids, at 28 per cent compared to 69 per cent. Their research has now been published in the Expert Review of Respiratory Medicine following a lengthy period of scrutiny and peer review.

The Huddersfield academics' work highlights the issues involved in scrutinising scientific evidence, as well as costs involved in research and the UK's preference for evidence-based practice. Oxford University's RECOVERY trial came to similar conclusions as the Huddersfield researchers in mid-June, leading to the UK government's decision that dexamethasone could be made available to patients, a move subsequently taken around the world.

The World Health Organisation (WHO) had, early in the pandemic, recommended that steroids should not be used to combat CoViD-19 due to perceived risk of delayed coronavirus clearance. Despite warnings from WHO, various global bodies acknowledged the mortality benefits of using steroids on COVID-19 patients with ARDS, such as the National Health Commission & State Administration of Traditional Chinese Medicine (NHC), Surviving Sepsis Campaign (SSC), and the National Institute of Health (NIH).

"What this shows is that providing evidence is not cheap," says Dr Merchant. "It comes at a very high cost; it not only costs time and money but may even cost precious lives. The background of the pandemic highlights this, it's something that we have known for years but unfortunately has been thrown into sharp relief by coronavirus," he adds.

"There is always a dilemma of the risks versus the benefits of evidence-based practice in a medical emergency," says Dr Hasan. "The WHO advice confused a lot of people and many countries stayed away from using steroids due to risks of diminishing immune response."

Dr Merchant adds that, "The benefits of using steroids outweighs the risks. There is a risk that the immune system may go down and there is a possibility of delayed viral clearance from the body, but this is a risk worth taking if it saves lives."

Their work has now been published in the Expert Review of Respiratory Medicine following peer review. The other authors in the study included Toby Capstick, a consultant pharmacist on respiratory medicine at Leeds Teaching Hospitals NHS Trust, Syed Tabish Zaidi, Associate Professor in Pharmacy at the University of Leeds, Chia Siang Know, a clinical pharmacist from Malaysia, Faizan Mazhar, a researcher from Italy and Raees Ahmed, a consultant pulmonologist in Texas, USA.

The UK was among countries that steered away from using steroids until confirmed by a randomised controlled trial, but those that did not found using steroids helped to keep death rates from COVID-19 relatively low.

The UK is now using its stockpile of 200,000 doses of dexamethasone.

Credit: 
University of Huddersfield

New landmine detection method to reduce false alarm rates

image: The technology can be easily transported to conflict areas via Army unmanned ground vehicles such as the TALON from QinetiQ North America.

Image: 
US Army

RESEARCH TRIANGLE PARK, N.C. -- Landmines pose a serious threat in conflict areas, yet modern detection systems struggle to discriminate between explosives and clutter. A project funded by the Army developed a new method for landmine identification that will greatly reduce false alarm rates.

Fewer false alarms will significantly reduce the cost of humanitarian landmine clearance operations and provide greater road mobility by avoiding unnecessary route detours. With this new technology, landmines can be detected without digging.

Vadum, Inc., North Carolina State University, the Georgia Institute of Technology and the Army Research Office, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, collaborated to develop what's known as the Vibration-ENhanced Underground Sensing system, or VENUS.

"New concepts are rare in the area of landmine detection," said Dr. James Harvey, program manager, ARO. "This advance has the potential to be a game changer."

The Night Vision and Electronic Sensors Directorate of the U.S. Army CCDC C5ISR Center supported the research as a part of an Army Small Business Technology Transfer award managed by ARO.

Most conventional landmine detectors are based on detecting the electromagnetic signature of the mine itself, which can easily be confused with other buried metal objects or wet or magnetic soil patches.

With this new technology, published in the proceedings of the 2020 SPIE Defense & Commercial Sensing Conference, the small metal parts inside the landmine are stimulated to vibrate using a pulsed magnetic field.

Most other buried objects don't respond to the magnetic pulse and those that do have very different vibrational characteristics. The vibrations are detected by a unique high dynamic range vibrometer that can distinguish closely-spaced low-frequency vibrations.

"This new capability resulted from combining exciting results from several previous ambitious research projects and is an outstanding example of the transition from university basic research to new military and commercial technology capabilities," said Professor Michael Steer, a NC State research partner. "The mathematical algorithms behind the detection depend on understanding the details of the interaction of magnetic fields, radar pulses, and vibrating components within the landmine as well as with the properties of various soil and clutter objects. Advancing university physical models and analysis continue to support the improvement of the detection algorithms."

The Army awarded the research team an additional two-year Phase II STTR contract to mature its unique technology.

As part of that award, the research team will work to miniature and ruggedize the detection device for reliable outdoor testing at an Army range. The researchers also will collect data from real landmines in a variety of soil conditions and demonstrate the performance of the technology in demanding and stressing field conditions.

"Because conventional metal detectors and ground penetrating radar rely on similar same fields, it should eventually be possible to upgrade conventional systems with VENUS technology to maximize detection capability," said Dr. Josh Wetherington, principal Vadum researcher.

Credit: 
U.S. Army Research Laboratory

Study shows how a single gene drives aggression in wild songbird

image: White-throated sparrows come in two different morphs, the white-striped (left) and the tan-striped (right). The morphs have both different plumage and behaviors, making these wild songbirds a good model organism for the genetic basis of behavior.

Image: 
Photo by Jennifer Merritt

A new study shows how differentiation of a single gene changes behavior in a wild songbird, determining whether the white-throated sparrow displays more, or less, aggression. The Proceedings of the National Academy of Sciences (PNAS) published the research, led by neuroscientists at Emory University.

The researchers singled out an estrogen receptor from a complex of more than 1,000 genes known as a "supergene," or genetic material inherited together as a block. The work provides a rare look at how genomic divergence can lead to behavioral divergence in a vertebrate.

"Evolution has tinkered with the DNA sequence of a gene of this songbird, and we demonstrated that those little changes affect both the expression of the gene and the bird's behavior," says Emory graduate student Jennifer Merritt, first author of the paper.

Merritt is a PhD candidate in the lab of Donna Maney, senior author of the paper and an Emory professor of psychology.

"White-throated sparrows are common backyard birds found through most of North America," Merritt says. "What's remarkable about them is that they occur in two different morphs that have not only different plumage, but also different strategies for maximizing reproductive output. Both types of differences are caused by genetic differentiation of only one region of a single chromosome, and we know exactly where it is."

At some point during the evolution of a species, a chromosome can break and flip. This process, called an inversion, isolates the genes that are trapped inside, producing a supergene. In some cases, supergenes have led to distinct morphs within a single species -- individuals with the supergene and those without it.

In the case of the white-throated sparrows, the white-striped morph sports bright yellow, black and white stripes on its crown while the tan-striped morph has more muted, tan and grayish stripes. The white-striped birds, which all possess at least one copy of the rearranged chromosome, tend to be more aggressive and less parental than the tan-striped birds, which do not have the rearranged chromosome.

"Scientists have hypothesized for 100 years that inversions are important for the evolution of some of the complex behaviors that we see in nature," Maney says. "But inversions are challenging to understand because, when they turn into supergenes, all of the genes are inherited together. We already knew a lot about the natural history of the white-throated sparrow, as well as the biological mechanisms underlying its aggression. Using that knowledge, we were able to finally show the evolutionary role of a supergene at the molecular level."

The current paper builds on previous work by the Maney lab, a leader in connecting gene sequence with behavior in free-living animals. In 2014, the lab identified a hormone receptor --estrogen receptor alpha (ER-alpha) -- that appeared connected to the differences in the sparrows' aggression and parenting behaviors in the wild. The white-striped birds express this receptor at much higher levels than the tan-striped birds, and the more the expression, the more aggressive the bird.

"For this paper, we wanted to follow the genetic variation of ER-alpha all the way up to where it's expressed in the brain, and then to behavior, to see if we could trace the behavioral variation to variation in this one gene," Merritt says.

The birds sing to establish a territory. The rate at which they sing gives a measure of their level of aggression, along with the frequency at which they charge, or "attack," animals encroaching on what they consider their territory.

In field studies of white-throated sparrows in their natural habitat, the researchers showed that the more a bird expresses the supergene version of the estrogen receptor, the more vigorously it defends its territory.

The researchers then moved beyond the correlational work by taking an experimental approach. White-throated sparrows in the lab were given a substance to block expression of the ER-alpha gene and their aggression levels were measured. The results showed that when expression of that one gene was blocked, the aggression of the white-striped birds went down so they behaved like the tan-striped ones.

"We believe this is the first demonstration of how a single gene within a supergene drives changes in a social behavior in a wild vertebrate," Merritt says. She gives an analogy for the challenge involved: "Imagine each of the genes within a supergene as tributaries converging into a river, the behavior. And then taking a sample of water from the river and determining which tributary the sample came from."

The Maney lab is continuing to investigate a suite of other neuroendocrine genes captured by the chromosome rearrangement in the white-throated sparrow that are thought to be important players in the regulation of social behavior.

Credit: 
Emory Health Sciences

New 'nanopores' technique offers proof-of-concept of earlier, safer tumor detection

image: Specific detection of Point-Mutation-Position using biological nanopore

Image: 
Ryuji Kawano, TUAT

In recent years, a non-invasive biopsy method called liquid biopsy has shown promise as a potential alternative to tissue biopsy, currently the gold standard in cancer detection and diagnosis. A tissue biopsy sample--traditionally collected through a surgical procedure that may require general anesthesia, accompanied by the risk of complications that may occur from any surgery, from pain through to infection and pneumonia --is typically tested for specific genetic variations, also referred to as mutations, which may offer information on a clear optimal treatment for that cancer.

Liquid biopsies, on the other hand, identify the presence of tumor DNA fragments or cells circulating in bodily fluids like blood, urine or saliva - called circulating tumor DNA (ctDNA) - and spares patients from unnecessary harm. Unfortunately, the minute amount of ctDNA in bodily fluids and their short-lived nature remain a challenge for real-life applications.

But biotech researchers at the Tokyo University of Agriculture and Technology (TUAT) have developed a nanopore technique which, in laboratory tests, has shown potential to offer a powerful, quick-and-easy tool for mutation detection.

The findings are published on Aug 9th, 2020, in the peer-reviewed journal Small Methods published by Wiley-VCH.

Nanopore measurements, a third-generation genetic sequencing technology, passes a DNA molecule through a nano-scale hole, or 'pore.' As it transits the pore, the DNA nucleotide bases (adenine [A], cytosine [C], guanine [G], or thymine [T]) cause changes in electrical charge that are specific to each of those bases and which can be catalogued, much like passing sand through a series of sifters. Nanopore tech can also sense the translocation, or exchange of genetic material, of short DNA strands via a blocking of the electric current when the pore is open. In both cases, second-generation measurement run times last anywhere from 4-9 days. But nanopore measurements occur in real time.

The rapid and cheap nanopore technique is often used for whole genome sequencing, but its use for ctDNA analysis remains underdeveloped. Nanopore sequencing is skilled in long read-lengths (>10,000-50,000 nt). Sequencing ctDNA (~150 bp) needs earlier stage processing like giving multiple copies of the original ctDNA to stretch targets. While attempts at approaches using nanopore tech for directly ctDNA detection have been made, and are able to recognize the presence or absence of a single genetic mutation, so far, they have been unable to recognize the position of this mutation.

The TUAT method, based on statistical analysis of the length of time it takes for the genetic code to unzip, and of the blocking of the current, allowing both the presence and position of a mutation to be identified. It has so far only been used on short strips of genetic material, or oligonucleotides, not in real-world liquid biopsies.

"This is still at the proof-of-concept stage, but it is exciting not just because it could permit earlier detection," said Ryuji Kawano, one of the two engineers responsible for devising the new method, "but the technique could be used to assess the degree of metastasis [cancer growth] to how well anticancer drugs are working."

The researchers now hope to work with medical institutions to verify and catalog the location of mutations in ctDNA from a many different cancers in order to develop this method as a simple diagnostic method for a wide range of occurrences of the disease.

Credit: 
Tokyo University of Agriculture and Technology

Ageing heart cells offer clues to susceptibility of older people to severe COVID-19

Genes that play an important role in allowing SARS-CoV-2 to invade heart cells become more active with age, according to research published today in the Journal of Molecular and Cellular Cardiology. The findings could help explain why age is major risk factor for dying from COVID-19, with people over 70 years at greatest risk, and why the disease can cause heart complications in severe cases, including heart failure and inflammation of the heart.

"When this novel coronavirus first emerged, we expected it to be primarily a respiratory illness, as the virus usually takes hold first in the lungs," said Professor Anthony Davenport from the Department of Medicine. "But as the pandemic has progressed, we've seen more and more COVID-19 patients - particularly older patients - affected by heart problems. This suggests that the virus is capable of invading and damaging heart cells and that something changes as we age to make this possible."

Professor Davenport led an international team of researchers from the University of Cambridge, Maastricht University, KU Leuven and Karolinska Institute to investigate the link between COVID-19 and heart failure. The researchers examined cells known as cardiomyocytes to see how susceptible they were to infection by the coronavirus. Cardiomyocytes make up the heart muscle and are able to contract and relax, enabling the heart to pump blood around the body. Damage to these cells can affect the ability of the heart muscles to perform, leading to heart failure

To cause damage, the virus must first enter the cell. SARS-CoV-2 is a coronavirus - spherical in shape with 'spike' proteins on its surface, which it uses to gain entry. The spike protein binds to ACE2, a protein receptor found on the surface of certain cells. The virus is also able to hijack other proteins and enzymes, including TMPRSS2 and Cathepsins B and L to gain entry.

The researchers compared cardiomyocytes from five young (19-25 year old) males and five older (63-78 year old) males and found that the genes that give the body instructions to make these proteins were all significantly more active in cardiomyocytes from the older males. This suggests that there is likely to be an increase in the corresponding proteins in aged cardiomyocytes.

"As we age, the cells of our heart muscles produce more of the proteins needed by the coronavirus to break into our cells," said Dr Emma Robinson from Maastricht University and KU Leuven. "This makes these cells more vulnerable to damage by the virus and could be one reason why age is a major risk factor in patients infected with SARS-CoV-2."

Some of the proteins encoded by the genes can be inhibited by existing medicines. For example, the anti-inflammatory drug camostat inhibits TMPRSS2 and has been shown to block SARS-CoV-2 entry in cells grown in the laboratory. The study also suggests new targets for medicines that could be developed such as compounds blocking binding of the virus to ACE2 that may be beneficial in protecting the heart.

"The more we learn about the virus and its ability to hijack our cells, the better placed we are to block it, either with existing drugs or by developing new treatments," said Professor Davenport.

Credit: 
University of Cambridge

Pothole repair made eco-friendly using grit from wastewater treatment

image: Researchers are turning grit from wastewater (left) into a ceramic mortar that can be used as pothole filler (right).

Image: 
Zhongzhe Liu

WASHINGTON, Aug. 18, 2020 -- Potholes are aggravating to drive over, and they can cause billions of dollars of damage every year to automobile wheels, tires and suspensions. Currently, road crews fill in these holes with hydrocarbon-containing asphalt, but that material can leach out, polluting the environment. Now, scientists report a brand-new way to repair roads that's also eco-friendly -- by using a remnant of wastewater treatment called grit that's usually disposed of in landfills.

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

"We had an idea to divert wastewater grit from landfills and turn it into a marketable product," says Zhongzhe Liu, Ph.D., who is presenting the work. "We formulated it into a ceramic mortar that could be used as a patch for pothole repair." The substance, known as grit assisted patch (GAP), is ultimately safer for the environment than hydrocarbon-based asphalt.

But grit, a heavy, unbiodegradable solid, requires processing to become GAP. First, wastewater containing sewage, food scraps and other waste is processed at treatment plants. The result is clean water that is released into waterways, but also solids from the preliminary treatment that are mostly sand and gravel, and this is referred to as grit. Because grit contains pathogens and impurities that make it unsuitable for direct recycling, it is usually taken to a landfill and buried.

Liu, who is at California State University-Bakersfield, and his collaborators were looking for ways to make grit useful, perhaps as a road material. They decided to incorporate it into a chemically bonded phosphate ceramic (CBPC). CBPCs are routinely used to treat hazardous or radioactive waste for disposal, but no one had used this yet on wastewater products.

Because a CBPC contains ingredients that would inactivate microbes, the researchers thought this could be a good way to kill pathogens and end up with a material that could be safely applied to roads. "In the first step of making a CBPC, we mix the wet grit with calcium oxide and magnesium oxide, which form an alkaline grit slurry that prevents the proliferation of pathogens," Liu says. "The second step is to add a weak acid, potassium dihydrogen phosphate, into the pathogen-minimized alkaline slurry to form the grit-CBPC mortar."

Conventional asphalt patch contains bitumen, a sticky, black residue left over after petroleum distillation. The conventional patch contains polycyclic aromatic hydrocarbons (known as PAHs) that are a risk to human health. A grit-formulated patch eliminates this environmental concern because its matrix is composed of calcium and magnesium oxides that are not toxic to people.

So far, the researchers have analyzed GAP performance in the lab, showing it has a compressive strength comparable to asphalt pavement, and they believe its longevity will be superior to that of asphalt-based patches. The group has filed a patent for GAP based on these initial findings. In the meantime, they are working on improving GAP's compressive strength even further, so it could potentially be used for other applications, such as building wheel stops at the end of parking spots.

The next step for getting GAP on the market as a pothole patch is to evaluate its bond strength when in contact with existing pavement and its durability when exposed to environmental extremes. The team is currently working on demonstration-scale experiments to field test GAP on an operational roadway with regular traffic. If necessary, they will explore additives to further improve the mechanical properties and durability of the new material. In addition, they plan to conduct a side-by-side comparison of GAP and conventional patch to gain a thorough understanding of the advantages it provides in terms of carbon footprint and economic benefit.

Credit: 
American Chemical Society

Novel method of heat conduction could be a game changer for server farms and aircraft

image: Lab member Mojtaba Edalatpour shows the thermal diode developed by Boreyko's team.

Image: 
Virginia Tech

Jonathan Boreyko, an associate professor in mechanical engineering, has developed an aircraft thermal management technology that stands ready for adaptation into other areas.

The research was published in Advanced Functional Materials on Aug. 18, 2020.

Boreyko was the recipient of a Young Investigator Research Program award in 2016, given by the Air Force Office of Scientific Research. This award funded the development of planar bridging-droplet thermal diodes, a novel approach to thermal management. Boreyko's research has shown this new approach to be both highly efficient and extremely versatile.

"We are hopeful that the one-way heat transfer of our bridging-droplet diode will enable the smart thermal management of electronics, aircraft, and spacecraft," said Boreyko.

Diodes are a special kind of device that allow heat to conduct in only one direction by use of engineered materials. For management of heat, diodes are attractive because they enable the dumping of heat entering one side, while resisting heat on the opposite side. In the case of aircraft (the focus of Boreyko's funding), heat is absorbed from an overheated plane, but resisted from the outside environment.

Boreyko's team created a diode using two copper plates in a sealed environment, separated by a microscopic gap. The first plate is engineered with a wick structure to hold water, while the opposite plate is coated with a water-repelling (hydrophobic) layer. The water on the wicking surface receives heat, causing evaporation into steam. As the steam moves across the narrow gap, it cools and condenses into dew droplets on the hydrophobic side. These dew droplets grow large enough to "bridge" the gap and get sucked back into the wick, starting the process again.

If the source of heat were instead applied the hydrophobic side, no steam can be produced because the water remains trapped in the wick. This is why the device can only conduct heat in one direction.

What does this look like in practice? An object producing heat, like a CPU chip, overheats if this heat is not continually removed. Boreyko's invention is affixed to this heat source. Generated heat is transferred through the conducting plate, into the water. Water turns to steam and moves away from the source of the heat. The hydrophobic, nonconducting side prevents heat from entering via the air or other heat sources that may be near, allowing the diode to manage the heat only from its main subject.

Boreyko's team measured a nearly 100-fold increase in heat conduction when the wicked side was heated, compared to the hydrophobic side. This is a significant improvement to existing thermal diodes. According to Boreyko, current diodes are either not very effective, only conducting a few times more heat in one direction, or require gravity. This new bridging-droplet thermal diode can be used upright, sideways, or even upside-down, and would even work in space where gravity is negligible.

Credit: 
Virginia Tech

New gene therapy approach eliminates at least 90% latent herpes simplex virus 1

image: A computer-generated image of a meganuclease (center), an antibody (left) and the gene-editing enzyme CRISPR-Cas9 (right). The light-colored ladder-like structures in the meganuclease and Cas9 images are the double helices of DNA in the genes they each target.

Image: 
Abigail Lambert / Stoddard Lab at Fred Hutch

Infectious disease researchers at Fred Hutchinson Cancer Research Center have used a gene editing approach to remove latent herpes simplex virus 1, or HSV-1, also known as oral herpes. In animal models, the findings show at least a 90 percent decrease in the latent virus, enough researchers expect that it will keep the infection from coming back.

The study, published August 18 in Nature Communications, used two sets of genetic scissors to damage the virus's DNA, fine-tuned the delivery vehicle to the infected cells, and targeted the nerve pathways that connect the neck with the face and reach the tissue where the virus lies dormant in individuals with the infection.

"This is the first time that scientists have been able to go in and actually eliminate most of the herpes in a body," said senior author Dr. Keith Jerome, professor in the Vaccine and Infectious Disease Division at Fred Hutch. "We are targeting the root cause of the infection: the infected cells where the virus lies dormant and are the seeds that give rise to repeat infections."

Most research on herpes has focused on suppressing the recurrence of painful symptoms, and Jerome said that his team is taking a completely different approach by focusing on how to cure the disease.

"The big jump here is from doing this in test tubes to doing this in an animal," said Jerome, who also leads the Virology Division at UW Medicine. "I hope this study changes the dialog around herpes research and opens up the idea that we can start thinking about cure, rather than just control of the virus."

Two-thirds of the world population under the age of 50 have HSV-1, according to the World Health Organization. The infection primarily causes cold sores and is lifelong.

In the study, the researchers used two types of genetic scissors to cut the DNA of the herpes virus. They found that when using just one pair of the scissors the virus DNA can be repaired in the infected cell. But by combining two scissors - two sets of gene-cutting proteins called meganucleases that zero in on and cut a segment of herpes DNA - the virus fell apart.

"We use a dual meganuclease that targets two sites on the virus DNA," said first author Martine Aubert, a senior staff scientist at Fred Hutch. "When there are two cuts, the cells seem to say that the virus DNA is too damaged to be repaired and other molecular players come in to remove it from the cell body."

The dual genetic scissors are introduced into the target cells by delivering the gene coding for the gene-cutting proteins with a vector, which is a harmless deactivated virus that can slip into infected cells. The researchers injected the delivery vector into a mouse model of HSV-1 infection, and it finds its way to the target cells after entering the nerve pathways.

The researchers found a 92% reduction in the virus DNA present in the superior cervical ganglia, the nerve tissue where the virus lies dormant. The reductions remained for at least a month after the treatment and is enough the researchers say to keep the virus from reactivating.

The team did other comparisons to fine-tune the gene editing approach:

- Gene cuts with meganucleases were more efficient that with CRISPR/Cas9.

- Refining the vector delivery mechanism, they found the adeno-associated virus (AAV) vector that was the most efficient at getting the gene edits to cells infected with the virus.

The researchers are pursuing a similar strategy for herpes simplex 2, which causes genital herpes. They expect it to take at least 3 years to move toward clinical trials.

"This is a curative approach for both oral and genital HSV infection," Aubert said. "I see it going into clinical trials in the near future."

Credit: 
Fred Hutchinson Cancer Center

Unraveling the initial molecular events of respiration

Respiration is a fundamental process of all living things, allowing them to produce energy, stay healthy, and survive. In cells, respiration involves what are known as "respiratory proteins", e.g. hemoglobin in the blood and myoglobin in muscles.

Respiratory proteins work by binding and releasing small molecules like oxygen, carbon monoxide etc., called ligands. They do this through their "active center", which in many respiratory proteins is a chemical structure called heme porphyrin.

Binding and releasing small molecules causes changes in the heme's molecular and electronic structure. Such a change is the transition from a planar low spin ligated porphyrin form to a domed high spin un-ligated form and vice-versa. This shift is a key step for respiration, ultimately switching hemoglobin between a "relaxed" and "tense" conformation.

Electrons spin around atoms, but also spin around themselves, and can cross over from one spin state to another. The debate about the transition from low-spin planar to a high-spin domed heme has been dominated by two schools of thought: the process is either by thermal relaxation or by a cascade among electron spin states.

Now, a team of scientists led by Majed Chergui at EPFL's School of Basic Sciences have solved the debate. The researchers detached the small molecule from the heme using short, energizing laser pulses. They then used another short, hard X-ray pulse from an X-ray free-electron laser to induce X-ray emission (XES), a very sensitive fingerprint of the spin state of molecules, which monitored the heme's changes as a function of time. They could thus determine that the passage from planar to domed and back is caused by a cascade among spin states.

The study was carried out on nitrosyl-myoglobin, which is myoglobin that has bound a nitric oxide molecule. Nitrosyl-myoglobin plays a crucial role in neurotransmission, regulation of vasodilatation, platelet aggregation, and immune responses.

"The conclusions of our work apply to all heme proteins," says Chergui. "In particular to hemoglobin in its uptake and release of oxygen when we breathe. Although this takes place at the thermal temperatures of the body, breathing is governed by electronic changes in the heme."

Credit: 
Ecole Polytechnique Fédérale de Lausanne