Culture

Swine coronavirus replicates in human cells

New research from the University of North Carolina at Chapel Hill suggests that a strain of coronavirus that has recently alarmed the swine industry may have the potential to spread to humans as well.

The coronavirus strain, known as swine acute diarrhea syndrome coronavirus (SADS-CoV), emerged from bats and has infected swine herds throughout China since it was first discovered in 2016. Outbreaks of such an illness have the potential to wreak economic havoc in many countries across the globe that rely on the pork industry.

The virus' potential threat to people was demonstrated in lab tests showing SADS-CoV efficiently replicated in human airway and intestinal cells. The findings were published Oct. 12 in PNAS.

Though it is in the same family of viruses as the betacoronavirus SARS-CoV-2, which causes the respiratory illness COVID-19 in humans, SADS-CoV is an alphacoronavirus that causes gastrointestinal illness in swine. The virus causes severe diarrhea and vomiting and has been especially deadly to young piglets.

SADS-COV is also distinct from two circulating common cold alphacoronaviruses in humans, HCoV-229E and HCoV-NL63.

"While many investigators focus on the emergent potential of the betacoronaviruses like SARS and MERS, actually the alphacoronaviruses may prove equally prominent -- if not greater -- concerns to human health, given their potential to rapidly jump between species," said Ralph Baric, professor of epidemiology at UNC-Chapel Hill Gillings School of Global Public Health.

While SADS-CoV has not been known to affect humans to-date, the COVID-19 pandemic serves as a potent reminder that many coronavirus strains found in animals have the potential to infect humans as well - an effect known as spillover.

The Baric lab worked with Caitlin Edwards, a research specialist and master of public health student at UNC-Chapel Hill, on the study which suggests humans may be susceptible to spillover of SADS-CoV.

Edwards, the study's first author, tested several types of cells by infecting them with a synthetic form of SADS-CoV to understand just how high the risk of cross-species contamination could be.

Evidence from the study indicates that a wide range of mammalian cells, including primary human lung and intestinal cells, are susceptible to infection. According to Edwards, SADS-CoV shows a higher rate of growth in intestinal cells found in the human gut, unlike SARS-CoV-2, which primarily infects lung cells.

Cross-protective herd immunity often prevents humans from contracting many coronaviruses found in animals. However, results from the testing done by Edwards and her team suggest that humans have not yet developed such immunity to SADS-CoV.

"SADS-CoV is derived from bat coronaviruses called HKU2, which is a heterogenous group of viruses with a worldwide distribution," Edwards said. "It is impossible to predict if this virus, or a closely related HKU2 bat strain, could emerge and infect human populations. However, the broad host range of SADS-CoV, coupled with an ability to replicate in primary human lung and enteric cells, demonstrates potential risk for future emergence events in human and animal populations."

In response to these findings, Edwards and colleagues tested the broad-spectrum antiviral remdesivir as a potential method of treatment for the infection.

Working with Gilead Sciences, remdesivir was developed by the Baric Lab to combat all known coronaviruses, including SADS-CoV. It is currently being used to treat COVID-19 infections in humans, including the United States president. Preliminary results from this study show that it has robust activity against SADS-CoV, though Edwards cautions that more testing is necessary on additional cell types and in animals to confirm these findings.

"Promising data with remdesivir provides a potential treatment option in the case of a human spillover event," she said. "We recommend that both swine workers and the swine population be continually monitored for indications of SADS-CoV infections to prevent outbreaks and massive economic losses."

SADS-CoV could also pose a threat to the U.S. economy, which was third in global pork production in 2019. In 2012, the U.S. pork industry was devastated by different swine coronavirus that emerged from China.

"Not surprisingly, we are currently looking for partners to investigate the potential of SADS-CoV vaccine candidates to protect swine," Baric said. "While surveillance and early separation of infected piglets from sows provide an opportunity to mitigate larger outbreaks and the potential for spillover into humans, vaccines may be key for limiting global spread and human emergence events in the future."

Credit: 
University of North Carolina at Chapel Hill

An innovative method to tune lasers toward infrared wavelengths

image: A laser optical pulse (blue) enters from the left into the hollow-core fibre filled with nitrogen gas (red molecules) and, along propagation, experiences a spectral broadening towards longer wavelengths, depicted as an orange output beam (right). This nonlinear phenomenon is caused by the Raman effect associated with the rotations of the gas molecules under the laser field, as schematically illustrated in the bottom panel.

Image: 
Riccardo Piccoli (INRS)

Researchers at Institut national de la recherche scientifique (INRS) have discovered a cost-effective way to tune the spectrum of a laser to the infrared, a band of great interest for many laser applications. They collaborated with Austrian and Russian research teams to develop this innovation, which is now the subject of a patent application. The results of their work were recently published in Optica, the flagship journal of the Optical Society (OSA).

In this field of study, many laser applications have a decisive advantage if the laser wavelength is located and possibly tunable in the infrared region. However, this is still hardly the case with current ultrafast laser technologies, and scientists need to explore various nonlinear processes to shift the emission wavelength. In particular, the Optical Parametric Amplifier (OPA) has so far been the only well-established tool to reach this infrared window. Although OPA systems offer a broad range of tunability, they are complex, often made of multiples stages, and quite expensive.

The team of Professor Luca Razzari, in collaboration with Professor Roberto Morandotti, has demonstrated that large wavelength tunability can also be achieved with a simple and much less expensive system: a hollow-core (capillary) fiber filled with nitrogen. In addition, this approach readily delivers optical pulses shorter than those of the input laser and with high spatial quality. The researchers also had the benefit of INRS expertise in this field, since the special system to stretch and hold such fibers is marketed by the startup few-cycle.

Asymmetrical spectral broadening

Usually, hollow-core fibers are filled with a monatomic gas such as argon in order to symmetrically broaden the spectrum of the laser and then recompress it into a much shorter optical pulse. The research team discovered that by using a molecular gas such as nitrogen, spectral broadening was still possible, but in an unexpected manner.

"Rather than spreading symmetrically, the spectrum was impressively shifted toward less energetic infrared wavelengths. This frequency shift is the result of the nonlinear response associated with the rotation of the gas molecules and, as such, it can be easily controlled by varying the gas pressure (i.e., the number of molecules) in the fiber," explains Dr. Riccardo Piccoli, who led the experiments in Razzari's team.

Once the beam is broadened toward the infrared, the researchers filter the output spectrum to keep only the band of interest. With this approach, energy is transferred into the near-infrared spectral range (with efficiency comparable to that of OPAs) in a pulse three times shorter than the input, without any complex apparatus or additional pulse post-compression system.

An international collaboration

To complete the research, the INRS scientists joined with Austrian and Russian colleagues. "We pooled our expertise after discovering at a conference how similar the phenomena our two groups had observed were," says Razzari.

The team of researchers based in Vienna headed by Professor Andrius Baltuska and Dr. Paolo A. Carpeggiani had a complementary strategy to that of INRS. They also used a nitrogen-filled hollow-core fiber, but rather than filtering the spectrum, they compressed it in time with mirrors capable of adjusting the phase of the broadened pulse. "In this case, the overall shift in the infrared was less extreme, but the final pulse was much shorter and more intense, perfectly suited to attosecond and strong-field physics" says Dr. Carpeggiani.

The Moscow-based team, led by Professor Aleksei Zheltikov, focused on developing a theoretical model to explain these optical phenomena. By combining these three approaches, the researchers were able to fully understand the complex underlying dynamics as well as achieve not only the extreme red shift using nitrogen, but also efficient pulse compression in the infrared range.

The international team believes the method could very well meet the increasing demand for long-wavelength ultrafast sources in laser and strong-field applications, starting with less expensive industrial-grade tunable systems based on the emerging ytterbium laser technology.

Credit: 
Institut national de la recherche scientifique - INRS

Machine learning model helps characterize compounds for drug discovery

WEST LAFAYETTE, Ind. - Tandem mass spectrometry is a powerful analytical tool used to characterize complex mixtures in drug discovery and other fields.

Now, Purdue University innovators have created a new method of applying machine learning concepts to the tandem mass spectrometry process to improve the flow of information in the development of new drugs. Their work is published in Chemical Science.

"Mass spectrometry plays an integral role in drug discovery and development," said Gaurav Chopra, an assistant professor of analytical and physical chemistry in Purdue's College of Science. "The specific implementation of bootstrapped machine learning with a small amount of positive and negative training data presented here will pave the way for becoming mainstream in day-to-day activities of automating characterization of compounds by chemists."

Chopra said there are two major problems in the field of machine learning used for chemical sciences. Methods used do not provide chemical understanding of the decisions that are made by the algorithm, and new methods are not typically used to do blind experimental tests to see if the proposed models are accurate for use in a chemical laboratory.

"We have addressed both of these items for a methodology that is isomer selective and extremely useful in chemical sciences to characterize complex mixtures, identify chemical reactions and drug metabolites, and in fields such as proteomics and metabolomics," Chopra said.

The Purdue researchers created statistically robust machine learning models to work with less training data - a technique that will be useful for drug discovery. The model looks at a common neutral reagent - called 2-methoxypropene (MOP) - and predicts how compounds will interact with MOP in a tandem mass spectrometer in order to obtain structural information for the compounds.

"This is the first time that machine learning has been coupled with diagnostic gas-phase ion-molecule reactions, and it is a very powerful combination, leading the way to completely automated mass spectrometric identification of organic compounds," said Hilkka Kenttämaa, the Frank Brown Distinguished Professor of Analytical Chemistry and Organic Chemistry. "We are now introducing many new reagents into this method."

The Purdue team introduces chemical reactivity flowcharts to facilitate chemical interpretation of the decisions made by the machine learning method that will be useful to understand and interpret the mass spectra for structural information.

Credit: 
Purdue University

Blood tests could be developed to help predict pregnancy complications new study suggests

UCLA researchers say a blood test commonly used to detect fetal genetic abnormalities may help predict complications associated with pregnancy before symptoms develop. Their preliminary study, appearing in Epigenetics, links certain cell-free DNA signatures to adverse outcomes in pregnancy, including ischemic placental disease and gestational diabetes.

The findings are the first to show that genetic material shed from the placenta into the mother's blood (circulating cell-free nucleic acids) during the first trimester of pregnancy could potentially be used to predict these potentially serious complications.

Although the analysis of genetic material in the mother's blood has been used to screen for genetic abnormalities in a pregnancy, this is the first time these specific methods have been used as a way of a more accurate prediction.

"Our research points to a promising approach that could improve outcomes for mothers and their babies using existing technologies," said Dr. Sherin Devaskar, lead author of the study and physician-in-chief of UCLA Mattel Children's Hospital and distinguished professor of pediatrics at the David Geffen School of Medicine. "If confirmed in larger studies, cell-free DNA blood tests may help identify issues in the placenta as an indicator of a healthy mother and fetus."

Researchers followed a diverse group of pregnant women between February 2017 and January 2019, testing their blood periodically throughout gestation. By the end of the study, 160 participants had given birth, with 102 maternal and 25 cord plasma samples taken along the way. They found that during the first-to-early second trimester, placenta-specific DNA increased among those women who went on to develop gestational diabetes. They also identified several differently expressed genes and were able to create a model with a predictive value for adverse pregnancy outcomes.

"The novelty of this research is being able to break down a mother's DNA and be able to hone in on the health of the placenta - something that researchers have never been able to do before," added Devaskar. "This research warrants application of automated methodologies in multi-center trials to improve future testing and screening for all women."

Credit: 
Taylor & Francis Group

Before the US general election, evidence of agreement -- and division -- on climate issues

WASHINGTON, DC--Just one month before an election in which climate change may be a key issue, new survey results show that climate change may be less politically polarizing than many might expect.

Climate Insights 2020: Partisan Divide--the fourth installment in a series of survey reports by researchers at Stanford University, Resources for the Future, and ReconMR--illustrates climate-related beliefs, attitudes, and policy preferences across the political spectrum. The survey, which polled 999 American adults from May to August 2020, identifies the issues on which political groups agree--and disagree. And although there are situations in which opinions differ along party lines, there is also bipartisan support on a number of issues related to climate change.

Topline Findings

94% of Democrats believe climate change has been happening, as do 67% of Republicans.

Majorities of Republicans (56%), Independents (77%), and Democrats (86%) believe that they have personally seen the effects of climate change.

Majorities of Republicans (53%), Independents (71%), and Democrats (96%) favor pursuing the goals of the Paris Agreement.

Majorities of all three groups think that the US government should act to deal with climate change.

43% of Democrats attach extreme personal importance to climate change, compared to 22% of Independents and 4% of Republicans.

"While some observers have claimed that climate change is a deeply partisan issue, the data show more nuance--majorities of all three groups of Americans agree on the existence, causes, and threat of climate change, as well as on various government policies that could be used to mitigate future warming," report co-author Jon Krosnick said. "And the partisan gap dividing American public opinion on this issue is smaller than it is on many other important issues facing the country."

To learn more about these findings, read the partisan divide installment of Climate Insights 2020 by Bo MacInnis, lecturer at Stanford University and PhD economist, and Jon Krosnick, social psychologist at Stanford University and RFF university fellow. The Climate Insights 2020 interactive data tool also allows users to explore the data in greater depth.

Future report installments in this series will focus on electric vehicles and a state-level breakdown. Previous installments of reports focus on overall trends, natural disasters, and climate policies.

Credit: 
Resources for the Future (RFF)

How deadly parasites 'glide' into human cells

image: Molecular structure of essential light chain protein in Plasmodium glideosome. The blue "clouds" represent electron density of the protein, with bonds between atoms indicated in yellow and water molecular indicated in red. The crystal structure at 1.5 Å phased by Sulphur-SAD was obtained using the Petra III beamline, at EMBL Hamburg.

Image: 
Samuel Pazicky/EMBL

Gliding movements to invade host cells

In biological terms, gliding refers to the type of movement during which a cell moves along a surface without changing its shape. This form of movement is unique to parasites from the phylum Apicomplexa, such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have an enormous impact on global heath. Plasmodium causes 228 million malaria infections and around 400,000 deaths per year. Toxoplasma, which infects even one third of the human population, can cause severe symptoms in some people, and is particularly dangerous during pregnancy.

Gliding enables the Apicomplexa parasites to enter and move between host cells. For example, upon entering the human body through a mosquito bite, Plasmodium glides through human skin before crossing into human blood vessels. This type of motion relies on actin and myosin, which are the same proteins that enable muscle movement in humans and other vertebrates. Myosin has a form of molecular 'legs' that 'march' along actin filaments and thereby create movement.

In Apicomplexa, myosin interacts with several other proteins, which together form a complex called the glideosome. The exact mechanism by which the glideosome works is not well understood, among other reasons because the molecular structure of most glideosome proteins are unknown. Yet understanding this mechanism could aid the development of drugs that prevent the assembly of the glideosome and thereby stop the progression of diseases such as malaria and toxoplasmosis.

Molecular stilts facilitate gliding

Scientists at EMBL Hamburg analysed the molecular structure of essential light chains (ELCs), which are glideosome proteins that bind directly to myosin. It is known that they are necessary for gliding, but their exact structure and role were unknown until now. The researchers now obtained molecular structures of ELC bound to myosin A in Toxoplasma gondii and Plasmodium falciparum using X-ray crystallography and nuclear magnetic resonance (NMR).

Their study, published in Communications Biology, shows that ELCs work like 'molecular stilts' - upon binding myosin A, the ELCs become rigid, and start to act as its lever arm. This stiffening lets myosin makes longer steps, which likely accelerates the parasite's gliding movements.

The researchers also investigated the role of calcium, a presumed gliding regulator, in the interaction between ELCs and myosin A. Surprisingly, they discovered that calcium does not influence the structure of ELCs. It does, however, increase the stability of the ELC-myosin A complex. This unexpected result shows that the glideosome architecture still hides many unknowns.

"This work has provided the first glimpse of how these organisms move around," says Matthew Bowler, an EMBL Grenoble researcher not involved in this study, who investigates Toxoplasma's strategies to control the immune system after invading cells.

"It is fascinating to see new molecular details emerge on how these parasites work outside of the host cell. The beautiful structures show how the motor that drives this motion is put together, and could provide a basis to develop new medicines to treat these diseases," continues Bowler.

Maria Bernabeu, who leads research on vascular dysfunction in cerebral malaria at the EMBL site in Barcelona, adds: "Plasmodium passage through the skin is the first stage of human infection. The advantage of targeting Plasmodium at that stage is that only about a hundred parasites are present. Understanding the parasite's gliding motility might help to develop drugs or vaccines that target Plasmodium before it multiplies."

Interdisciplinary collaboration

The work is a result of interdisciplinary collaboration between structural biologists (Löw group) and parasitologists (Gilberger group) from the European Molecular Biology Laboratory in Hamburg and Centre for Structural Systems Biology (CSSB), as well as scientists from the Bernhard Nocht Institute for Tropical Medicine, University of Hamburg and Martin-Luther-University Halle-Wittenberg. It demonstrates the potential of interdisciplinary collaborations in contributing to our understanding of biological processes and possible future strategies to combat parasitic diseases.

"Entering malaria research has been an exciting endeavour - regular exchange with experts and the interdisciplinary environment helped us to explore the field of parasitology," says Christian Löw.

Credit: 
European Molecular Biology Laboratory

Evolution: No social distancing at the beginning of life

video: Bacteria are the dominant form of life that inhabit every available environment on Earth. This includes human bodies, where they outnumber our cells and genes, and regulate our existence for good and bad. Bacteria are regularly viewed as simple single-celled organisms. As bacteria are ancient, it is also widely accepted that a bacteria-like unicellular being was the first life. However, a recent work published in Molecular Biology and Evolution by an international research team challenges these long held views.
In this study the researchers took evolutionary tools to study the growth of biofilms, the most common bacterial lifestyle characterized by the tight clustering of bacterial cells on surfaces. Surprisingly, they found that the development of bacterial biofilms is comparable to animal embryogenesis. This means that bacteria are true multicellular organisms just like we are. Considering that the oldest known fossils are bacterial biofilms, it is quite likely that the first life was also multicellular, and not a single-celled creature as considered so far, explain the researchers in their study. The video shows Bacillus growth mirroring the embryonic development.

Image: 
Dr Momir Futo, postdoctoral researcher, Laboratory of Evolutionary Genetics, Rudjer Boskovi? Institute

Bacteria are a dominant form of life that inhabit every environment on Earth. This includes human bodies, where they outnumber our cells and genes and regulate our existence for good or bad. Bacteria are regularly viewed as simple, single-celled organisms. As bacteria are ancient, it is widely accepted that a bacteria-like, unicellular being was the first life. Recent work published in 'Molecular Biology and Evolution' by an international research team challenges these views.

In this paper the researchers took evolutionary tools to study the growth of biofilms, the most common bacterial lifestyle characterized by the tight clustering of bacterial cells on surfaces. "Surprisingly, we found that the development of bacterial biofilms is comparable to animal embryogenesis. This means that bacteria are true multicellular organisms just like we are. Considering that the oldest known fossils are bacterial biofilms, it is quite likely that the first life was also multicellular, and not a single-celled creature as considered so far," explains Prof Tomislav Domazet-Lošo from the Rudjer Boskovic Institute and the Catholic University of Croatia in Zagreb who led the research.

Secret life of bacterial biofilms

Macroscopic organisms like animals and plants are never germ-free. They are always accompanied by bacteria and other microorganisms that persist on their inner and outer surfaces. Yet, these symbiotic bacteria are just a tiny fraction of the bacterial diversity that occupy every bit of the biosphere including vast subterranean habitats in the Earth's crust. In all of these sites bacterial cells are locally organized in morphologically structured clusters known as biofilms. Beside natural habitats, biofilms are also extremely important in industrial and biomedical settings where they often lead to biofouling or persistent infections that are resistant to therapies.

For some time, microbiologist have recognized that bacterial cells live a rich social life in biofilms, however it has remained obscure if these diverse interactions make a multicellular organism. "Evolutionary methods to study collective behavior of cells in animal development were at hand, but no one tried to transfer this technology from animal embryos to bacterial biofilms. Perhaps people were uncomfortable to challenge the special status of animal multicellularity, the idea that is culturally hardwired," emphasises Domazet-Lošo.

Technology translation

Previous work of Domazet-Lošo and his team was focused on evolutionary genomics and animal development. They were able to show that the evolution is mirrored in embryos, thus confirming more than 150 years old conjecture that ontogeny parallels phylogeny in animals. To reach these findings, they developed a computational approach, named genomic phylostratigraphy, that allows evolutionary dating of genes and proteins on the large scale. Now together with researchers from University of Zagreb, Chalmers University and Technical University of Denmark they further refined this tool to meet specifics of bacteria. "We generated the first phylostratigraphic maps of bacteria and this allowed us to link bacterial phenotypes in biofilms to evolutionary information," continues Domazet-Lošo.

Bacillus biofilms behave like animal embryos

In order to feed their new bioinformatic pipeline, researchers sampled biofilms of Bacillus subtilis, a model organism for biofilm research that inhabits soil as well as human gut. Using transcriptome sequencing and protein quantification they established transcript and protein expression levels for all Bacillus genes during the process of biofilm growth.

"Surprisingly, we found that evolutionary younger genes were increasingly expressed towards the later timepoints of biofilm growth. In other words, we found that Bacillus ontogeny strongly recapitulates phylogeny. So far, these patterns have been considered the signature of embryo development in complex eukaryotes." stresses Domazet-Lošo. The research team then followed the trail and looked for other features of embryogenesis in biofilms like stage-organized architecture, increased use of multicellularity genes and molecular links to morphology changes, and to their excitement they found these properties as well.

Towards the control of biofilms

These findings challenge the special status of eukaryotic multicellularity and show that bacteria are more complex than we thought. The tools developed in this study could also help in finding efficient procedures for biofilm control - a largely unsolved problem in industry and medicine.

"Our results point that a biofilm should be viewed as a multicellular individual, and not as a pile of individual cells. Like in animal embryogenesis, every developmental phase has its own peculiarities. Critical transition stages in biofilm growth could now be targeted via their stage-specific genes that we detected. This could be a game changer in treating biofilm related diseases, and in preventing industrial losses." concludes Domazet-Lošo.

Credit: 
Ruđer Bošković Institute

COVID-19 frequently causes neurological injuries

Without directly invading the brain or nerves, the virus responsible for COVID-19 causes potentially damaging neurological injuries in about one in seven infected, a new study shows. These injuries range from temporary confusion due to low body-oxygen levels, to stroke and seizures in the most serious cases, say the study authors.

Led by researchers at NYU Grossman School of Medicine, the study showed no cases of brain or nerve inflammation (meningitis or encephalitis), indicating no immediate invasion of these organs by the pandemic virus, SARS-CoV-2.

While this should reassure patients, the neurological complications of COVID-19 should be taken seriously because they dramatically raise a patient's risk of dying while still in hospital (by 38 percent), researchers say. Such adverse effects also raise a coronavirus patient's likelihood (by 28 percent) of needing long-term or rehabilitation therapy immediately after their stay in hospital.

"The results of our study showed no signs that the coronavirus directly attacks the nervous system," says study lead investigator Jennifer Frontera, MD. "The neurological complications seen in COVID-19 are predominately the secondary effects of being severely ill and suffering from low oxygen levels in the body for prolonged periods of time," says Frontera, a professor in the Department of Neurology at NYU Langone Health.

Published in the journal Neurology online Oct. 5, the study closely monitored the progress of 606 COVID-19 adult patients diagnosed with brain or other nerve-related medical conditions at any of four NYU Langone hospitals in New York City and Long Island between March 10 and May 20, when coronavirus infections were at their peak in the region.

Frontera says that ahead of the pandemic, dozens of NYU Langone neurologists and trainees had deployed across its medical centers to assist with the expectant surge of COVID-19 patients.

Early reports from Asia and Europe, where infections had spiked before rising in the United States, she says, had also "raised the alarm" about possible brain damage from coronavirus infection. Because of this, the research team was ready to look for any signs of neurological dysfunction among the thousands of patients being admitted to hospital in the spring. Among all the hospitals, 4,491 patients tested positive for COVID-19 during that time.

Among the study's other key results was that common neurological problems, such as confusion caused by chemical electrolyte imbalances, severe infection or kidney failure, usually arose within 48 hours of developing general COVID-19 symptoms, including fever, difficulty breathing, and cough.

Half of those neurologically affected were over the age of 71, which researchers say is significantly older than the other 3,885 patients with COVID-19 (at a media age of 63) who did not experience brain dysfunction. Most were men (66 percent) and white (63 percent). Frontera notes that the study results do suggest that Blacks are not at greater risk of neurological complications than other COVID-19 patients, which is "welcome news," given that Blacks are widely known to be at greater risk of death from coronavirus infection. However, she says this potentially important observation requires further investigation.

While the coronavirus is known to attack other organs, including blood vessels and the heart, researchers say its main target is the lungs, where it makes breathing difficult, starving the body of oxygen it needs to stay alive. Low levels of oxygen in the body and brain was another common neurological problem, study results showed, that could lead to confusion, coma, or permanent brain damage.

"Our study results suggest that physicians need to be more aggressive in stabilizing body oxygen levels in patients with COVID-19 as a potentially key therapy for stopping, preventing and/or possibly reversing neurological problems," says study senior investigator Steven Galetta, MD.

Credit: 
NYU Langone Health / NYU Grossman School of Medicine

Scientists release previously unseen footage showing environmental impacts of pot fishing

video: Video footage captured by scientists showed numerous species suffered damage as the pots were hauled from the seabed

Image: 
University of Plymouth

The global pot fishing industry could be having a greater impact on corals, sponges and other species found on the seabed than previously thought, according to new research.

Scientists from the University of Plymouth (UK) attached video cameras to pots used by crab and lobster fishermen off the south coast of England.

As the pots were lowered, and later recovered, they recorded any damage caused to the rocky reefs on the seabed and various ecologically important species which call them home.

The resulting footage showed that of the 18 species observed, 14 suffered damage as the pots were hauled from the seabed.

This included certain species - including pink sea fans, ross coral, Dead Man's Fingers and boring sponges - recognised as indicators of general health in the marine environment.

The findings go against previous thinking around the damage caused by pot fishing to the seabed, with research carried out until now regarding its potential impact as minimal.

Writing in Marine Environmental Research, scientists say they must now be taken into consideration by authorities and fishing communities, and that managers must balance ecology with social and economic considerations to determine what level of impact is acceptable. This is especially important where potting is occurring within MPAs.

Crustacean fisheries are a very valuable component of the UK fishing industry and are particularly important to coastal communities, with 1,342 vessels fishing with pots and traps in 2016 and the majority of them measuring under 10m and operating in inshore waters.

In 2017, total shellfish landings accounted for 38% of all those by UK vessels, with 34,100 tonnes of crab and lobster (worth almost £100million) landed into the UK. Globally, the industry is present in 48 countries which also have multi-use MPAs within their waters.

Dr Sarah Gall, Lecturer in Marine Conservation at the University of Plymouth, led the research as part of her PhD studies. She said: "This is the first study to quantify the true footprint of potting. Despite finding that areas fished with pots were characterised by species indicative of a healthy reef system, we have not seen the greater abundance, species richness and diversity we might have expected. The footage we obtained shows that 25-30% of seabed species were either damaged or dislodged by potting and we have also highlighted particular concerns about some long-lived and slow-growing species. The future management of pot fisheries will need to address these findings on a site by site basis to ensure the long term health of our rocky reef systems and the sustainability of the potting industry."

The study was carried out in partnership with fishermen operating in the Inshore Potting Agreement (IPA) area, which stretches along the South Devon coastline from Plymouth Sound to Start Point. It was funded by the Devon & Severn Inshore Fisheries and Conservation Authority and the University's own Marine Institute.

It builds on the University's extensive research into the impact of conservation initiatives such as Marine Protected Areas (MPAs), which includes a long-running monitoring programme in Lyme Bay, off the Dorset and Devon coast.

That research has previously shown that restricting the amount of inshore potting for crab and lobster within MPAs can generate a "win-win" for both fishermen and the marine environment.

Dr Emma Sheehan, Associate Professor of Marine Ecology, leads the Lyme Bay Project and is senior author on the current paper. She added: "Our ongoing work in Lyme Bay has shown that smaller fishing communities recognise the importance of preventing damage to the environment in order to secure their livelihoods in the long term. In that respect, this study is crucial because it provides the first evidence of a potentially global issue and those in the industry are integral to addressing it. Through working with conservation and coastal managers, we hope a solution could be reached where the interests of industry and the environment can be balanced."

Credit: 
University of Plymouth

Eyeglass-attached display device provides fluoroscopic guidance during spine surgery

image: A: The surgeon views the standard fluoroscopic monitor by turning the head away from the surgical field. B: The surgeon uses the smart glasses display device as an alternative method to display fluoroscopic images, and so the surgeon's focus can be maintained on the surgical field.

Image: 
Copyright 2020 AANS.

CHARLOTTESVILLE, VA (OCTOBER 13, 2020). The authors, two surgeon-researchers from Murayama Medical Center in Tokyo, tested a device that, when attached to everyday eyeglasses, can display fluoroscopic images used for surgical guidance directly to the surgeon. Without such a device, the surgeon must receive this guidance by repeatedly looking across the operating room to a video monitor. The authors found that the eyeglass display device allowed the surgeon to focus on operative tasks more efficiently and resulted in a slightly shorter length of surgery and less exposure to radiation.

Detailed findings of this study can be found in a new article, "Smart glasses display device for fluoroscopically guided minimally invasive spinal instrumentation surgery: a preliminary study," by Keitaro Matsukawa, MD, PhD, and Yoshiyuki Yato, MD, PhD, published today in the Journal of Neurosurgery: Spine.

An operating room can be a very crowded place. In addition to surgical equipment and personnel, there are numerous intraoperative support systems, including navigation systems that aid the surgeon in performing complicated surgeries. Navigation systems are particularly important when surgery is minimally invasive. However, their placement in the operating room may not be totally convenient to the surgeon.

Fluoroscopy is a form of medical imaging that produces real-time moving X-ray images that visualize a patient's bone anatomy. In minimally invasive spine surgery, in which the surgical opening is small, fluoroscopy provides the surgeon with a clear view of where and how to affix surgical screws, plates, and other spinal instrumentation.

When fluoroscopy is used, spine surgeons must turn their heads repeatedly to view both the surgical field and the fluoroscopy monitor, which normally stands several feet away from the operating table. This constant movement can be distracting for the surgeon. The authors suggest that it also may cause longer operative times and technical difficulties, and lead to potential errors. The authors hypothesized that wearing a device that displays fluoroscopic images within the surgeon's visual field during insertion and attachment of spinal instrumentation could improve the safety of minimally invasive spine surgery.

To test their hypothesis, the authors performed a pilot prospective randomized study in 20 patients who underwent posterior lumbar interbody fusion at the L5-S1 spinal level. To the authors' knowledge, this is the first study on the feasibility of using a wearable display device for fluoroscopically guided, minimally invasive, spinal instrumentation surgery. All surgeries were performed by the same surgeon and, in each case, the percutaneous pedicle screw technique was used.

In 10 cases the surgeon wore glasses with an attached device (picoLinker device, Westunitis) that wirelessly displayed real-time fluoroscopic images within the surgeon's visual field. In the other 10 cases the surgeon wore no display device, but instead frequently consulted the fluoroscopy monitor that was positioned elsewhere in the OR.

To examine whether the wearable display device improved aspects of spine surgery, the authors examined, in each group of patients, the number of times the surgeon's head turned to consult the fluoroscopic video display, the duration of the operation, and the length of time the patient and surgeon were exposed to radiation emitted by the fluoroscope.

The surgeon turned toward the fluoroscopy monitor significantly fewer times while wearing the eyeglass-attached fluoroscopic display device (means ± standard deviations: 0.1 ± 0.31 vs. 82.4 ± 32.5 times; p

After reviewing the results, the authors conclude that an eyeglass-attached fluoroscopic display device "may be a valid option to enhance the surgeon's ability to concentrate on operative tasks by improving ergonomic efficiency during surgery."

When asked about the findings of this study, the authors responded, "We believe the major advantages are 'concentration' and 'information centralization.' The smart glasses display system used as an alternative screen in front of surgeons' eyes allows them to see both the surgical field and information displayed on monitors simultaneously without moving the eyes and head. In addition to fluoroscopic images, a variety of other images, such as those obtained before surgery and those from vital sign monitors, neurophysiological monitors, computer navigation monitors, and endoscopic monitors, can be displayed on the wearable screen. The eyeglass-attached display device can be a great tool to help surgery progress smoothly and safely."

Credit: 
Journal of Neurosurgery Publishing Group

The ur-Iris likely had purple flowers, pollinated by insects for nectar

image: Selected Iris species. (A) I. atropurpurea; (B) I. bismarckiana; (C) I. fulva; (D) I. historio; (E) I. loretti; (F) I. lutescens; (G) I. mesopotamica;
(H) I. petrana; (I) I. pumila; (J) I. reticulata; (K) I. setosa; (L) I. virginica

Image: 
The authors

The genus Iris of flowering plants -- named after the Greek rainbow goddess because of the variation in flower color -- comprises over 300 species across the northern hemisphere, some of which are Vulnerable or (Critically) Endangered on the IUCN Red List of Threatened Species. Due to the poor fossil record, it is not yet known when irises first originated, but scientists believe the genus is only a few million years old, having its closest living relatives in today's southern Africa.

"We wanted to study the factors influencing and maintaining the outstanding evolutionary divergence in irises, a young but very diverse group. We were especially interested in the evolution of flower color and morphology, because these are key traits for pollinator attraction," says Dr Yuval Sapir from the School of Plant Sciences of Tel Aviv University, Israel, corresponding author of a new study in the open-access journal Frontiers in Plant Science.

Modern Iris species mostly live in (semi-)deserts or mountainous environments, although some specialize in moist or wet habitats. They are typically pollinated by insects, but a few species are visited by birds, and often capable of self-fertilization ("self-compatible"). Their flowers have three upright petals, the "standards", and three hanging sepals, the "falls". Standards and falls aren't always the same color, and can be dark purple, violet, pink, yellow, or white. Their lower parts form a pollination tunnel that contains both the stamens and styles, whose entrance may be marked by a ridge or "crest", part of the falls. Crests are thought to function as guides to lead potential pollinators to the nectar or pollen reward. Falls may also bear a raised hairy area, the "beard", with possibly similar function. Some species don't produce nectar but provide another type of reward for insects: safe shelter inside the flowers, which warm up in the morning. Such species often have a dark "spot" on the falls, which may play a role in increasing or maintaining a higher temperature inside.

Given this diversity, what might the last common ancestor of irises have looked like?

"Here we show that the ancestor of the genus Iris probably had purple flowers, with a crest and a spot on the falls. Its flowers were also likely insect-pollinated, producing nectar as a reward, and self-compatible. From this point onward, rapid evolution created divergence to hundreds of combinations of color, size, and other flower characteristics," says Dr Katarzyna Roguz, a postdoctoral scientist who led the research.

Roguz et al. created a phylogeny or evolutionary tree, based on the similarity in DNA sequence from public databases at six genes -- five from the chloroplast and one from the nucleus -- from 215 species, 10 subspecies, and two varieties of Iris. Each scored for 16 traits related to flower color, reproduction, habitat, and distribution. The phylogeny largely supported the published taxonomy of the genus Iris, divided into seven subgenera (Limniris, Iris, Hermodactyloides, Nepalensis, Pardanthopsis, Scorpiris, Xiphium), with a further division into two and six sections for the largest subgenera, Limniris and Lophiris.

The researchers show that many traits of irises are evolutionary labile -- that is, shifting back-and-forth between alternate states. For example, spots were lost and regained repeatedly, while shifts between purple versus yellow flowers were common. Beards also evolved at least three times independently. While the overwhelming majority of irises remain insect-pollinated, there have been at least two shifts towards bird pollination, followed by several reversals back to insect pollination. Other traits were shown to be more evolutionary stable, for example mating system and the ability to produce nectar, where shifts between the states were few.

"Our results suggest that pollinators are responsible, at least partially, for the evolution of Iris flower shape and that they are still playing a major role in the divergence of species in this genus. Evolution is amazing!" says Sapir.

Credit: 
Frontiers

Oncotarget: miR-708-5p targets oncogenic prostaglandin E2 production in lung cancer cell

image: miR-708 and the arachidonic acid pathway. Illustration of miR-708's relationship to the AA signaling pathway. Blue lettering indicates short-lived intermediates and mature signaling molecules within the AA pathway. Red lettering illustrates a negative correlation between miR-708 and AA-related gene's mRNA expression in LUSC patients. Green lettering illustrates a positive correlation between miR-708 and AA-related gene's mRNA expression in LUSC patient. Black lettering illustrates no significant correlation. Solid black lines indicate metabolic steps, while dotted black lines indicate eicosanoid signaling to respective receptors. (**) Represents predicted miR-708 targets from microRNA. org and miRTarBase.

Image: 
Correspondence to - Carol S. Lutz - lutzcs@njms.rutgers.edu

Volume 11, Issue 26 of Oncotarget reported that Lung cancer is of particular importance, as it is the deadliest cancer worldwide.

In this study, the authors show that high mi R-708 expression is associated with survival rates in lung squamous cell carcinoma patients. mi R-708 also represses PGE2 production by suppressing both COX-2 and mPGES-1 expression in lung cancer cells.

Moreover, mi R-708 decreases proliferation, survival, and migration of lung cancer cells, which can be partially attributed to mi R-708's inhibition of PGE2 signaling.

Lastly, they identify novel mi R-708 predicted targets and possible regulators of mi R-708 expression in lung cancer.

Collectively, these data demonstrate that dysregulated mi R-708 expression contributes to exacerbated PGE2 production, leading to an enhanced pro-tumorigenic phenotype in lung cancer cells.

Dr. Carol S. Lutz from The Department of Microbiology, Biochemistry, and Molecular Genetics at Rutgers Biomedical & Health Sciences, New Jersey Medical School, School of Graduate Studies in Newark New Jersey USA said, "Lung cancer is the most common cancer, with more than 2.09 million lung cancer cases worldwide in 2018."

More importantly, lung cancer is the deadliest cancer in the world, with more than 1.79 million lung cancer-related deaths in 2018.

Lung cancer is a collection of several distinct subtypes, with non-small cell lung cancer accounting for 85% of all lung tumors. mi R-708 also indirectly regulates the expression of genes involved in PI3K signaling, cell cycle progression, epithelial-mesenchymal transition, and cancer cell stemness.

In this study, the authors aim to decipher novel mi R-708 targets and suggest a solution to the controversy on whether mi R-708 is an oncogenic or tumor-suppressive mi RNA in lung cancer.

The Lutz Research Team concluded in their Oncotarget Research Paper that collectively, their findings suggest further study of mi R-708 in lung cancer.

The data paired with previous studies highlight a potential value for mi R-708 as a diagnostic in differentiating lung tumors, as well as a potential therapeutic intervention, particularly in lung squamous cell carcinomas.

Their work has identified novel tumor-suppressive mi R-708 functions by suppressing oncogenic PGE2 production through targeting of COX-2 and mPGES-1.

"Their work has identified novel tumor-suppressive mi R-708 functions by suppressing oncogenic PGE2 production through targeting of COX-2 and mPGES-1"

These findings could be the foundation for identifying novel mi R-708 targets, as well as regulators of mi R-708 expression in cancer.

Moreover, the study highlights the need to better understand lung cancer biology to improve the diagnosis and treatment of lung cancer, ultimately aiming to increase positive patient outcomes.

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DOI - https://doi.org/10.18632/oncotarget.27614

Full text - https://www.oncotarget.com/article/27614/text/

Correspondence to - Carol S. Lutz - lutzcs@njms.rutgers.edu

Keywords -
miR-708-5p,
miR-708,
lung cancer,
COX-2,
mPGES-1

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Journal

Oncotarget

DOI

10.18632/oncotarget.27614

Credit: 
Impact Journals LLC

Athletes don't benefit from relying on a coach for too long

BINGHAMTON, NY -- Athletes increasingly relying on a coach over the course of a season may be a sign that they aren't progressing in their development, according to new research from Binghamton University.

On the other hand, inspirational coaches will find that their athletes will become less reliant on them over time.

"Being increasingly needed by your athletes as time goes on is not a good sign," says Chou-Yu Tsai, assistant professor of management in Binghamton University's School of Management. "If your athletes no longer need your leadership and guidance as time goes on, that should be seen as a positive sign that you've helped them in their development."

Tsai, who studies leadership in a number of contexts, including athletics, worked with a research team consisting of San-Fu Kao of National Tsing Hua University and Robert Schinke of Laurentian University. They set out to discover how a coach's leadership style affected athlete evaluations of their competency over time.

The researchers evaluated how nearly 250 Division I collegiate basketball players felt about their coaches at different points over the course of a season. They focused on a coach's ability to enact transformational leadership, or the ability to develop athletes to their full potential.

"Transformational coaches empower their players in ways beyond just playing a sport. They help players develop meaning and instill pride, and encourage them to go above and beyond for the good of the team," said Tsai.

They found that coaches who enacted high transformational leadership had a decrease in perceived coaching competency by their athletes over time. In other words, the more a coach inspired a player to achieve their full potential, the less the athlete relied on their coaching.

In contrast, they found that coaches with low transformational leadership skills had an increase in perceived coaching competency by their athletes over the course of the season. This means that players may rely more on their uninspiring coaches over time.

"If you're not gaining some sort of independence from your coach, you may feel like you need that coach even more," said Tsai. "This probably isn't a good sign."

Tsai said it's important for coaches to understand how their leadership style interacts with player perceptions of them.

"Coaches may incorrectly think they did something wrong if their athletes aren't as reliant on them anymore," said Tsai. "On the contrary, our research indicates that this kind of independence is a sign that you demonstrated good leadership behaviors."

As for how to become a transformational leader, Tsai recommends that coaches focus on the personal development of their athletes.

"Transformational coaches don't want athletes to only become better players. They mentor their athletes and help them become better people as well," said Tsai.

Credit: 
Binghamton University

Examining e-cigarette use among current, former smokers

What The Study Did: National survey data were used to look at how common electronic cigarette use is among U.S. adults, if they were current or former smokers and used e-cigarettes to help quit smoking.

Authors: Margaret Mayer, Ph.D., M.P.H., of the National Institutes of Health in Bethesda, Maryland, 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.2020.20694)

Editor's Note: The article includes 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

Children's pain 'swept under the carpet for too long' - Lancet Commission

When 12-year-old Caitriona Roberts went to her doctor because she was experiencing pain and swelling in her ankle, no one knew quite what was up.

Initially written-off as 'just a sprain' which would go away, she would spend the next six months living in almost constant pain until interventions from a diligent doctor referred her to a specialist who diagnosed juvenile idiopathic arthritis - an autoimmune condition the now 28-year-old has lived with and managed ever since.

Belfast resident Caitriona is not alone in experiencing chronic pain in childhood, which typically increases during puberty. Up to 10% of young people experience disabling chronic pain into early adulthood, with conditions including arthritis, other types of musculoskeletal pain, recurrent abdominal pain, and headaches. Yet, according to the authors of a major new report released today (Tuesday 13 October 23:30), how paediatric pain is recognised, assessed and treated has gone under the radar for too long.

The findings of the Lancet Child and Adolescent Health Commission, the first of its kind ever to address the issue, suggest that much more needs to be done to help young people like Caitriona by making pain matter across society. The research was led by the Centre for Pain Research at the University of Bath, supported by Versus Arthritis and the Mayday Fund, and reflects the views and opinions of multidisciplinary medical professionals, as well as patients, including Caitriona, whose experiences fed into the work.

The report suggests that change in paediatric services over the past 40 years in terms of pain recognition, diagnosis, assessment and management is slow. The last major intervention in the field came in the 1980s when, remarkably, for the first time, it was recognised that babies experienced pain - astonishingly, up until that point, a number of routine and major operations, including for heart surgery, were carried out without anaesthetics. The report speculates that much of what we do (or fail to do) for children in pain today might come to be seen as unwise, unacceptable or unethical in the next 40 years.

In calling for four key goals - to make childhood pain matter, to make it understood, to make it visible and to make it better - the authors argue that there must be widespread recognition that too many children live with pain and that not enough is being done to support them from diagnosis through to management of long-term conditions. These goals range from 'biological' (e.g. medication) to psychological treatment / management (e.g. CBT) and to social support (e.g. better support for parents, schools and careers). Achieving these goals would transform the lives of children for the better they say.

Dr Emma Fisher, Versus Arthritis Career Development Fellow at the University of Bath, who led the work explains: "Among health-care professionals, it is easy to agree that no child should experience pain if that pain can and should be prevented, avoided, or successfully treated. In practice, however, we know there is ample evidence that children frequently experience preventable pain, and that in high-income settings, with advanced health-care systems and highly educated and regulated health professionals, children and young people experience pain that often goes unnoticed, unreported, or is not responded to, across healthcare including in the Emergency Department, post-surgical care, and in tertiary care.

"This really matters, both for those experiencing pain and those around them but also across wider society. We know that chronic pain experienced in childhood is likely to feed through to adulthood and this has long-term health and economic costs associated. This Lancet Child and Adolescent Health Commission is a call to action on funders, researchers and policymakers more broadly to sit up and listen to the fact that too many of our young people are in pain and need help."

Among its many recommendations, the Lancet Child and Adolescent Health Commission calls for an end to children experiencing pain when receiving routine vaccinations, drawing on the findings and recommendations from a seminal study published in 2015. Dr Fisher adds: "For many parents and children, a trip to the doctors for routine inoculations will be a stressful and painful experience. This does not have to be the case - we know how we can make the experience less painful for young people, but we're not doing it. This is just another example of how pain has been accepted as an everyday feature of growing up."

Professor Christopher Eccleston, Director of the Centre for Pain Research at the University of Bath, explains: "In this report we present four transformational goals: to make pain matter, be understood, visible, and better. We need to advance our understanding of pain, especially in paediatrics, and we need to translate our discovery to improve the lives of people in pain. Building on today's Lancet Child and Adolescent Health Commission, we need to find better ways to break out of our silos and work together as researchers, funders and policymakers to make quick and effective progress and ensure that young people like Caitriona have a different and better pain journey."

Caitriona agrees. She has been working with the researchers from Bath, the USA, Canada, Europe, and New Zealand on this report, adding her voice on behalf of a community of young people who are living with pain. She adds: "I think this issue has been swept under the carpet for too long. Still today, over 15 years on from my diagnosis with arthritis, I find people, including medical professionals, unaware of the condition or its effects on my day-to-day life. And when I speak to other young people, I find that sadly, very little seems to have changed in terms of how they experience pain or the support they receive.

"I was lucky. I was diagnosed by an incredible doctor - Dr Rooney - who not only identified my condition after others ignored it, but who worked with me throughout childhood and beyond. She really understood the effects of arthritis on my life, not just the physical ones but the emotional too and she helped me so much: she really deserves an award. Not everyone is as lucky, which is why the issues the report raises are so important."

Having completed two degrees from Queens and Ulster in Northern Ireland, Caitriona now works in law, alongside volunteering for Versus Arthritis helping other young people going through similar diagnoses. "Versus Arthritis were so pivotal in supporting me when I was first diagnosed that it's fantastic to be able to give back and help other young people. Working together and talking as a community we're able to share our experiences and shape interventions like this. And when you can help people in that way, well, there is no better feeling."

Zoe Chivers, Head of Services at Versus Arthritis who co-funded the Lancet Child and Adolescent Health Commission says: "People living with arthritis deal with the dismissal of their condition every day and the Commission findings detail the consequences of this for children in pain.

"Parents tell us about the struggle they have convincing their GP that their child's illness is more than growing pains; we know that the existence of specialist child rheumatology services can make the difference between walking to school or needing a wheelchair. While the focus, attention, and dedication in providing quality services to children is consistently in place for conditions like cancer it's woefully absent for childhood arthritis and chronic pain.

"As a society we need to understand that dismissal of arthritis comes at high price and that adults and children living in pain with the condition should no longer be expected to pay it."

Credit: 
University of Bath