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New COVID-19 content from Annals of Internal Medicine

Below please find link(s) to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A complete collection is available at https://annals.org/aim/pages/coronavirus-content.

1. NFL employee and player surveillance program enabled early detection of COVID-19, even among those who were asymptomatic

Free full text: https://www.acpjournals.org/doi/10.7326/M21-0319

Frequent, routine testing within the National Football League (NFL) enabled early detection of COVID-19 infection among players and employees, even among those who were asymptomatic. The study is among the first to summarize the use of daily testing for COVID-19 surveillance. A brief research report is published in Annals of Internal Medicine.

Researchers from the NFL and IQVIA studied results for more than 600,000 tests administered to over 11,600 NFL players and staff during the 2020 football season to describe results of a rigorous, large-scale COVID-19 testing and monitoring program. Testing was conducted daily using 2 reverse transcription polymerase chain reaction (RT-PCR) platforms: a transcription mediated amplification platform, and an antigen point-of-care. Test results were reported as "positive," "negative," "presumptive positive," or "inconclusive." Cycle thresholds (Cts), which can approximate viral load, were reported where possible. In addition to routine testing, the Program included ongoing player and staff education, physical distancing and masking requirements, environmental disinfection, and contact tracing protocols to decrease risk for transmission.

That data showed that overall, frequent RT-PCR surveillance allowed for detection of new infections, including those early in the clinical course and patients who were not experiencing symptoms at the time of testing. Quantitative values proved useful for understanding test results, with Ct values signaling early infection. The researchers noted that antigen POC testing was unable to reliably rule out COVID-19 early in infection.

According to the authors, these findings may be used to inform understanding and development of population-level SARS-CoV-2 testing and surveillance strategies to mitigate spread of the virus.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. For more information or to speak with the corresponding authors, please contact Megan Grant at Megan.Grant@nfl.com.

2. Vaccination rates in urban hospital less than ideal, especially among Black and Hispanic employees

Free full text: https://www.acpjournals.org/doi/10.7326/M21-1513

A brief research report found that vaccination rates of health care system employees during the COVID-19 pandemic were less than ideal, particularly among Black and Hispanic people. Understanding SARS-CoV-2 vaccination among health care workers is important because they are at high risk for occupational exposure and may be convincing advocates for vaccination among their patients. The findings are published in Annals of Internal Medicine.

Researchers from The MetroHealth System and Case Western Reserve University studied health records for more than 7,800 employees in an urban safety-net hospital system to determine the relationship between social and demographic characteristics of health care workers and receipt of vaccination. They found sizeable disparities in vaccination rates by race/ethnicity and occupational category. Adjusted probability of vaccination among Black employees was approximately 30% and about 55% among Hispanics. This rate was highest among Asian employees at about 68% and about 65% among Whites. Physicians, dentists, and psychologists had the highest rate of vaccination (81%), while nurses (54%) and facilities staff had the lowest (35%).

According to the researchers, these findings are concerning given the high burden of COVID-19 affecting in Black and Hispanic communities. The low vaccination rate among nurses was also deemed concerning given their higher rate of occupational exposure to SARS-CoV-2 and likely higher risk for death due to COVID-19. Understanding SARS-CoV-2 vaccination among health care workers is important because they are at high risk for occupational exposure and may be convincing advocates for vaccination among their patients. Barriers to vaccination cannot explain low uptake, as availability, efficacy, and safety of the vaccines were widely publicized to all employees by e-mail, intranet, flyers posted on bulletin boards, and word of mouth and vaccination scheduling could occur at any time via patient portal or by telephone. These findings suggest that more must be done to understand and overcome barriers to vaccination among health care employees and especially for Black and Hispanic populations.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To speak with the corresponding author, J. Daryl Thornton, MD, MPH, please contact Dorsena Drakeford at ddrakeford@metrohealth.org.

3. Medicalized hotels a safe alternative to conventional hospitals for patients with noncritical COVID-19 infection

Free full text: https://www.acpjournals.org/doi/10.7326/M21-1873

A team of researchers from Hospital Clinic de Barcelona (HCB) found that medicalized hotels are a safe alternative to conventional hospitals for patients with noncritical COVID-19 infection. Their brief research report is published in Annals of Internal Medicine.

During the first wave of the pandemic in Barcelona, the Catalonia Plaza Hotel in Barcelona was medicalized to provide hospital-level care to patients with COVID-19. Staff from different HCB departments were recruited to work in the hotel hospital (HH). From March to May 2020, 2,410 patients with COVID-19 were admitted to HCB and about one fifth of those patients were transferred to the HH. The cumulative median length of stay was 15 days for the HCB and HH combined and 9 days for the HH. Just over 5% of the patients in the HH required transfer back to HCB because of clinical deterioration or other medical complications and 2 of those patients died.

According to the researchers, these finding suggest that medicalized hotels can be used to reduce pressure on hospitals, allowing them to be used for patients who are more complex and critically ill. Their report provides preliminary guidance on how to adapt of hotels for medical use and how to determine admission criteria for selecting appropriate patients.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To speak with the corresponding author, David Nicolás, MD, PhD, please contact HCB PR at premsa@clinic.cat or Ms. Núria Boutin nboutin@clinic.cat.

4. NIH panel discusses lessons learned from developing treatment guidelines during a pandemic health crisis

Free full text: https://www.acpjournals.org/doi/10.7326/M21-1647

In March 2020, the White House Coronavirus Task Force, through the Secretary of Health
and Human Services, asked the National Institutes of Health (NIH) to develop evidence-based
guidelines for the treatment of patients with COVID-19. In a new commentary published in Annals of Internal Medicine, members of the National Institutes of Health COVID-19 Treatment Guidelines Panel discuss the important lessons the process has provided for responding to an unprecedented public health emergency.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To speak with the corresponding authors, Safia Kuriakose, PharmD, and Kanal Singh, MD, MPH, please contact the NIAID Office of Communications and Government Relations at 301-402-1663 or niaidnews@niaid.nih.gov.

Credit: 
American College of Physicians

For transplant recipients, third time may be the charm for better COVID vaccine protection

image: Johns Hopkins Medicine researchers have shown that three doses of vaccine against SARS-CoV-2 -- the virus that causes COVID-19 -- increase antibody levels more than the standard two-dose regimen for people who have received solid organ transplants. The researchers say this finding suggests booster doses should be investigated for those who are immunocompromised.

Image: 
Graphic created by M.E. Newman, Johns Hopkins Medicine, with public domain images and background artist rendition of SARS-CoV-2 courtesy of the U.S. Centers for Disease Control and Prevention

In a study published today in the Annals of Internal Medicine, Johns Hopkins Medicine researchers say they believe that, for the first time, there is evidence to show that three doses of vaccine increase antibody levels against SARS-CoV-2 -- the virus that causes COVID 19 -- more than the standard two-dose regimen for people who have received solid organ transplants.

"Our findings suggest clinical trials are warranted to determine if transplant recipients should receive COVID-19 vaccine booster doses as standard clinical practice, similar to what is currently done with hepatitis B and influenza vaccinations for this population," says study lead author William Werbel, M.D., an infectious diseases research fellow at the Johns Hopkins University School of Medicine.

People who receive solid organ transplants (such as hearts, lungs and kidneys) often must take drugs to suppress their immune systems and prevent rejection. Such regimens may interfere with a transplant recipient's ability to make antibodies to foreign substances, including the protective ones produced in response to vaccines.

In the first of two previous studies, the researchers showed that only 17% of the participating transplant recipients produced sufficient antibodies after one dose. Then, in the second study, they found the level improved to 54% after the second shot. In both cases, even those transplant recipients with antibodies had levels well below what has been typically seen in people with healthy immune systems.

In their latest study, the researchers evaluated 30 organ transplant recipients who received a third dose of one of three vaccines -- Johnson & Johnson/Jansen, Moderna or Pfizer/BioNTech -- between March 20 and May 10, 2021. They had previously received two doses of either the Moderna or Pfizer/BioNTech vaccine. The median age of the study participants was 57, 17 were women and one identified as non-white. No study participant reported an illness prior to vaccination or a positive test for SARS-CoV-2. All were taking multiple immunosuppressive medications to prevent rejection of their transplanted organs.

"Our findings revealed that a third of the participants who had negative antibody levels and all who had low positive levels before the booster increased their immune response after a third vaccine dose," says study senior author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine.

A week after receiving their third vaccine dose, 23 study participants completed a questionnaire about adverse effects. Reactions were generally mild or moderate, with one participant reporting severe arm pain and another a severe headache. No participant reported fever or an allergic reaction. There was one case of mild organ rejection during the study.

"These reactions seem acceptable, considering the benefits that vaccines can confer," says Segev.

Werbel and Segev note that this study only examined antibody levels, and that future research is needed to see if the increased immune response after a third vaccine dose is associated with lower SARS-CoV-2 infection rates.

"Although the third vaccine dose appears to raise the immune response of transplant recipients to higher levels than after one or two doses, these people may still be at greater risk for SARS-CoV-2 infection than the general population who have been vaccinated," says Werbel. "Therefore, we recommend that transplant recipients and other immunocompromised people continue to wear masks, maintain physical distancing and practice other COVID-19 safety measures."

Credit: 
Johns Hopkins Medicine

University of Washington researchers can turn a single photo into a video

video: UW researchers have developed a deep learning method that can produce a seamlessly looping, realistic looking video from a single photo. Here is B-roll: examples of Palouse Falls and Snoqualmie Falls in the state of Washington.

Image: 
University of Washington

Sometimes photos cannot truly capture a scene. How much more epic would that vacation photo of Niagara Falls be if the water were moving?

Researchers at the University of Washington have developed a deep learning method that can do just that: If given a single photo of a waterfall, the system creates a video showing that water cascading down. All that's missing is the roar of the water and the feeling of the spray on your face.

The team's method can animate any flowing material, including smoke and clouds. This technique produces a short video that loops seamlessly, giving the impression of endless movement. The researchers will present this approach June 22 at the Conference on Computer Vision and Pattern Recognition.

"A picture captures a moment frozen in time. But a lot of information is lost in a static image. What led to this moment, and how are things changing? Think about the last time you found yourself fixated on something really interesting -- chances are, it wasn't totally static," said lead author Aleksander Holynski, a doctoral student in the Paul G. Allen School of Computer Science & Engineering.

"What's special about our method is that it doesn't require any user input or extra information," Holynski said. "All you need is a picture. And it produces as output a high-resolution, seamlessly looping video that quite often looks like a real video."

Developing a method that turns a single photo into a believable video has been a challenge for the field.

"It effectively requires you to predict the future," Holynski said. "And in the real world, there are nearly infinite possibilities of what might happen next."

The team's system consists of two parts: First, it predicts how things were moving when a photo was taken, and then uses that information to create the animation.

To estimate motion, the team trained a neural network with thousands of videos of waterfalls, rivers, oceans and other material with fluid motion. The training process consisted of asking the network to guess the motion of a video when only given the first frame. After comparing its prediction with the actual video, the network learned to identify clues -- ripples in a stream, for example -- to help it predict what happened next. Then the team's system uses that information to determine if and how each pixel should move.

The researchers tried to use a technique called "splatting" to animate the photo. This method moves each pixel according to its predicted motion. But this created a problem.

"Think about a flowing waterfall," Holynski said. "If you just move the pixels down the waterfall, after a few frames of the video, you'll have no pixels at the top!"

So the team created "symmetric splatting." Essentially, the method predicts both the future and the past for an image and then combines them into one animation.

"Looking back at the waterfall example, if we move into the past, the pixels will move up the waterfall. So we will start to see a hole near the bottom," Holynski said. "We integrate information from both of these animations so there are never any glaringly large holes in our warped images."

Finally, the researchers wanted their animation to loop seamlessly to create a look of continuous movement. The animation network follows a few tricks to keep things clean, including transitioning different parts of the frame at different times and deciding how quickly or slowly to blend each pixel depending on its surroundings.

The team's method works best for objects with predictable fluid motion. Currently, the technology struggles to predict how reflections should move or how water distorts the appearance of objects beneath it.

"When we see a waterfall, we know how the water should behave. The same is true for fire or smoke. These types of motions obey the same set of physical laws, and there are usually cues in the image that tell us how things should be moving," Holynski said. "We'd love to extend our work to operate on a wider range of objects, like animating a person's hair blowing in the wind. I'm hoping that eventually the pictures that we share with our friends and family won't be static images. Instead, they'll all be dynamic animations like the ones our method produces."

Credit: 
University of Washington

Regenerating damaged eyes with mussel protein and amniotic membrane

image: Schematic illustration of sutureless amniotic membrane transplantation (AMT) using a visible light-activated mussel protein-based hydrogel adhesive (FixLight).

Image: 
POSTECH

The eye is the first sensory organ that recognizes the presence or shape of an object. The conjunctiva is a thin mucous membrane that covers the front half of the eyeball. It protects the eye by secreting mucus and tears for lubrication, and prevents microorganisms from entering. However, since it is exposed to the air, it is susceptible to damages by microorganisms, bacteria, or dust. In fact, if fibrovascular tissues are left to propagate on its surface, they can lead to diseases like pterygium, which can cause visual deterioration. To treat such conditions, an operation to remove and regenerate the damaged conjunctiva is performed. Recently, a Korean research team has developed a new method for performing sutureless amniotic membrane transplantation using the mussel adhesive protein.

Professor Hyung Joon Cha's research team at POSTECH (Ph.D. candidate Seong-Woo Maeng, Dr. Tae Yoon Park) with the team led by Professor Woo Chan Park of the Department of Ophthalmology at Dong-A University College of Medicine (Dr. Ji Sang Min, currently at Kim's Eye Hospital of the Konyang University School of Medicine) have together applied a light-curable protein bioadhesive named FixLight to an animal model that simulated the transplantation of the amniotic membrane on an actual ocular surface. As a result, it was confirmed that the operation could be completed more than five times faster than the traditional suture method and the therapeutic effect of the conjunctival regeneration through stably bonded amniotic membranes could successfully replace the conventional procedure.

The amniotic membrane is the innermost membrane of the placenta that surrounds and protects the embryo. Since it contains many factors that promote epithelial regeneration, performing amniotic transplantation to reconstruct the ocular surface has been widely practiced. However, the current method stitches the membrane with sutures and fixes it to the surface of the eyeball, which leaves a scar. And since precise sutures are required due to the thinness of the amniotic membrane, the operation is considerably time-consuming.

To this, the POSTECH research team has developed a light-curable adhesive that exists in a liquid state when unexposed to light, but changes into a hydrogel within a few seconds when exposed to visible light of a specific wavelength. Going a step further this time, in joint effort with researchers from Dong-A University College of Medicine, the amniotic membrane was transplanted without sutures on the ocular surface of a rabbit model with conjunctiva defects using a light-curable bioadhesive.

The joint research team used a visible light-curable bioadhesive with liquid-solid photocrosslinking characteristics in the amniotic membrane transplantation surgery, focusing on the high transparency of the amniotic membrane. After evenly coating the liquid adhesive, the amniotic membrane was adhered to the defect site by crosslinking it with light of a specific wavelength. In an experiment using a rabbit conjunctiva defect model, the researchers observed stable tissue adhesion ability that showed no significant difference from suture-treated cases even on the wet surface of the eye. In addition, after epithelialization progressed over the transplanted amniotic membrane, the adhesive completely biodegraded and regenerated into an integrated epithelial tissue.

Professor Hyung Joon Cha of POSTECH explained, "We confirmed the effectiveness of a new amniotic membrane transplantation method for conjunctival reconstruction in an actual animal model using the mussel adhesive protein, an original biomaterial." He added, "It is anticipated to be highly useful as a safe bioadhesive to replace sutures in various medical fields."

FixLight - the visible light-curable protein bioadhesive - shows promise for commercialization in the near future as it has completed the technology transfer to Nature Gluetech Co., Ltd. and is awaiting clinical trials as a safe bioadhesive that can fully replace surgical sutures.

"The amniotic membrane transplantation is an important operation in ocular surface reconstruction and this visible light-curable bioadhesive enabled facile and rapid operation," remarked Professor Woo Chan Park of Dong-A University College of Medicine. "This technique shows promise to be applicable to other ophthalmological surgeries such as closing of incisions after cataract operation or other transplantations of the ocular surface, such as conjunctival autografting."

Credit: 
Pohang University of Science & Technology (POSTECH)

Scientists make highly maneuverable miniature robots controlled by magnetic fields

image: The NTU millimeter-sized robots measure about the size of a grain of rice and can be controlled using magnetic fields.

Image: 
NTU Singapore

A team of scientists at Nanyang Technological University, Singapore (NTU Singapore) has developed millimetre-sized robots that can be controlled using magnetic fields to perform highly manoeuvrable and dexterous manipulations. This could pave the way to possible future applications in biomedicine and manufacturing.

The research team created the miniature robots by embedding magnetic microparticles into biocompatible polymers -- non-toxic materials that are harmless to humans. The robots are 'programmed' to execute their desired functionalities when magnetic fields are applied.

The made-in-NTU robots improve on many existing small-scale robots by optimizing their ability to move in six degrees-of-freedom (DoF) - that is, translational movement along the three spatial axes, and rotational movement about those three axes, commonly known as roll, pitch and yaw angles.

While researchers have previously created six DoF miniature robots, the new NTU miniature robots can rotate 43 times faster than them in the critical sixth DoF when their orientation is precisely controlled. They can also be made with 'soft' materials and thus can replicate important mechanical qualities -- one type can 'swim' like a jellyfish, and another has a gripping ability that can precisely pick and place miniature objects.

The research by the NTU team was published in the peer-reviewed scientific journal Advanced Materials in May 2021 and is featured as the front cover of the June 10 issue.

Lead author of the study, Assistant Professor Lum Guo Zhan from the School of Mechanical and Aerospace Engineering said the crucial factor that led to the team's achievement lie in the discovery of the 'elusive' third and final principal vector of these magnetic fields, which is critical for controlling such machines.

By contrast, previous works had only defined the applied magnetic fields in terms of two principal vectors.

"My team sought to uncover the fundamental working principles of miniature robots that have six-DoF motions through this work. By fully understanding the physics of these miniature robots, we are now able to accurately control their motions. Furthermore, our proposed fabrication method can magnetise these robots to produce 51 to 297 folds larger six-DoF torques than other existing devices. Our findings are therefore pivotal, and they represent a significant advancement for small-scale robotic technologies," explains Asst Prof Lum.

Remote-controlled miniature robots suitable for surgical, manufacturing use

Measuring about the size of a grain of rice, the miniature robots may be used to reach confined and enclosed spaces currently inaccessible to existing robots, say the NTU team, making them particularly useful in the field of medicine.

The movements of the robots can be controlled remotely by an operator, using a programme running on a control computer that precisely varies the strength and direction of magnetic fields generated by an electromagnetic coil system.

The miniature robots may also inspire novel surgical procedures for 'difficult-to-reach' vital organs such as the brain in future, the NTU team said, adding that much more work and testing still need to be accomplished before the miniature robots can eventually be deployed for their targeted medical applications.

Co-authors of the research, PhD students Xu Changyu and Yang Zilin from the School of Mechanical and Aerospace Engineering said, "Besides surgery, our robots may also be of value in biomedical applications such as assembling lab-on-chip devices that can be used for clinical diagnostics by integrating several laboratory processes on a single chip."

NTU miniature robots swim through barriers, assemble structures

In lab experiments, the research team demonstrated the dexterity and speed of the miniature robots.

Using a jellyfish inspired robot, the NTU team showed how it was able to swim speedily through a tight opening in a barrier when suspended in water. This demonstration was highly significant as it suggested that these robots were able to negotiate barriers in dynamic and uncertain environments and this could be a highly desirable ability for their targeted biomedical applications in future such as in surgical procedures for 'difficult-to-reach' vital organs such as the brain.

Demonstrating precise orientation control, the miniature robot also recorded a rotation speed of 173 degrees per second for their sixth DoF motion, exceeding the fastest rotation that existing miniature robots have achieved, which is four degrees per second for their sixth DoF motion.

With their gripper robot, the scientists were able to assemble a 3D structure consisting of a bar sitting atop two Y-shaped stilts in less than five minutes, about 20 times faster than existing miniature robots have been able to. This proof-of-concept demonstration, say the researchers, suggests that one day they may be used in 'micro factories' that build microscale devices.

Providing an independent view, Professor Huajian Gao, a Distinguished University Professor from the School of MAE at NTU, and a recipient of the prestigious 2021 American Society of Mechanical Engineers Timoshenko Medal, said, "This is a perfect example of how engineering ingenuity rooted in deep scientific understanding helps us develop advanced robotics for the benefit of mankind. This research work can have profound impact in many fields ranging from novel surgical methods to small scale assembly processes in future manufacturing."

The NTU team is now looking to make their robots even smaller, on the scale of a few hundred micrometres, and to ultimately make the robots fully autonomous in terms of control.

Credit: 
Nanyang Technological University

Study presents new species of bizarre, extinct lizard previously misidentified as a bird

image: Oculudentavis naga, as depicted in this artist's reconstruction, was a bizarre lizard that researchers initially struggled to categorize. They are still unsure of its exact position in the lizard family tree.

Image: 
Stephanie Abramowicz/Peretti Museum Foundation/Current Biology

GAINESVILLE, Fla. --- An international research team has described a new species of Oculudentavis, providing further evidence that the animal first identified as a hummingbird-sized dinosaur was actually a lizard.

The new species, named Oculudentavis naga in honor of the Naga people of Myanmar and India, is represented by a partial skeleton that includes a complete skull, exquisitely preserved in amber with visible scales and soft tissue. The specimen is in the same genus as Oculudentavis khaungraae, whose original description as the smallest known bird was retracted last year. The two fossils were found in the same area and are about 99 million years old.

Researchers published their findings in Current Biology today.

The team, led by Arnau Bolet of Barcelona's Institut Català de Paleontologia Miquel Crusafont,
used CT scans to separate, analyze and compare each bone in the two species digitally, uncovering a number of physical characteristics that earmark the small animals as lizards. Oculudentavis is so strange, however, it was difficult to categorize without close examination of its features, Bolet said.

"The specimen puzzled all of us at first because if it was a lizard, it was a highly unusual one," he said in an institutional press release.

Bolet and fellow lizard experts from around the world first noted the specimen while studying a collection of amber fossils acquired from Myanmar by gemologist Adolf Peretti. (Note: The mining and sale of Burmese amber are often entangled with human rights abuses. Peretti purchased the fossil legally prior to the conflict in 2017. More details appear in an ethics statement at the end of this story).

Herpetologist Juan Diego Daza examined the small, unusual skull, preserved with a short portion of the spine and shoulder bones. He, too, was confused by its odd array of features: Could it be some kind of pterodactyl or possibly an ancient relative of monitor lizards?

"From the moment we uploaded the first CT scan, everyone was brainstorming what it could be," said Daza, assistant professor of biological sciences at Sam Houston State University. "In the end, a closer look and our analyses help us clarify its position."

Major clues that the mystery animal was a lizard included the presence of scales; teeth attached directly to its jawbone, rather than nestled in sockets, as dinosaur teeth were; lizard-like eye structures and shoulder bones; and a hockey stick-shaped skull bone that is universally shared among scaled reptiles, also known as squamates.

The team also determined both species' skulls had deformed during preservation. Oculudentavis khaungraae's snout was squeezed into a narrower, more beaklike profile while O. naga's braincase - the part of the skull that encloses the brain - was compressed. The distortions highlighted birdlike features in one skull and lizard-like features in the other, said study co-author Edward Stanley, director of the Florida Museum of Natural History's Digital Discovery and Dissemination Laboratory.

"Imagine taking a lizard and pinching its nose into a triangular shape," Stanley said. "It would look a lot more like a bird."

Oculudentavis' birdlike skull proportions, however, do not indicate that it was related to birds, said study co-author Susan Evans, professor of vertebrate morphology and paleontology at University College London.

"Despite presenting a vaulted cranium and a long and tapering snout, it does not present meaningful physical characters that can be used to sustain a close relationship to birds, and all of its features indicate that it is a lizard," she said.

While the two species' skulls do not closely resemble one another at first glance, their shared characteristics became clearer as the researchers digitally isolated each bone and compared them with each other. The differences were minimized when the original shape of both fossils was reconstructed through a painstaking process known as retrodeformation, conducted by Marta Vidal-García from the University of Calgary in Canada.

"We concluded that both specimens are similar enough to belong to the same genus, Oculudentavis, but a number of differences suggest that they represent separate species," Bolet said.

In the better-preserved O. naga specimen, the team was also able to identify a raised crest running down the top of the snout and a flap of loose skin under the chin that may have been inflated in display, Evans said. However, the researchers came up short in their attempts to find Oculudentavis' exact position in the lizard family tree.

"It's a really weird animal. It's unlike any other lizard we have today," Daza said. "We think it represents a group of squamates we were not aware of."

The Cretaceous Period, 145.5 to 66 million years ago, gave rise to many lizard and snake groups on the planet today, but tracing fossils from this era to their closest living relatives can be difficult, Daza said.

"We estimate that many lizards originated during this time, but they still hadn't evolved their modern appearance," he said. "That's why they can trick us. They may have characteristics of this group or that one, but in reality, they don't match perfectly."

The majority of the study was conducted with CT data created at the Australian Centre for Neutron Scattering and the High-Resolution X-ray Computed Tomography Facility at the University of Texas at Austin. O. naga is now available digitally to anyone with Internet access, which allows the team's findings to be reassessed and opens up the possibility of new discoveries, Stanley said.

"With paleontology, you often have one specimen of a species to work with, which makes that individual very important. Researchers can therefore be quite protective of it, but our mindset is 'Let's put it out there,'" Stanley said. "The important thing is that the research gets done, not necessarily that we do the research. We feel that's the way it should be."

While Myanmar's amber deposits are a treasure trove of fossil lizards found nowhere else in the world, Daza said the consensus among paleontologists is that acquiring Burmese amber ethically has become increasingly difficult, especially after the military seized control in February.

"As scientists we feel it is our job to unveil these priceless traces of life, so the whole world can know more about the past. But we have to be extremely careful that during the process, we don't benefit a group of people committing crimes against humanity," he said. "In the end, the credit should go to the miners who risk their lives to recover these amazing amber fossils."

Other study co-authors are J. Salvador Arias of Argentina's National Scientific and Technical Research Council (CONICET - Miguel Lillo Foundation); Andrej Cernansky of Comenius University in Bratislava, Slovakia; Aaron Bauer of Villanova University; Joseph Bevitt of the Australian Nuclear Science and Technology Organisation; and Adolf Peretti of the Peretti Museum Foundation in Switzerland.

A 3D digitized specimen of O. naga is available online via MorphoSource. The O. naga fossil is housed at the Peretti Museum Foundation in Switzerland, and the O. khaungraae specimen is at the Hupoge Amber Museum in China.

The specimen was acquired following the ethical guidelines for the use of Burmese amber set forth by the Society for Vertebrate Paleontology. The specimen was purchased from authorized companies that are independent from military groups. These companies export amber pieces legally from Myanmar, following an ethical code that ensures no violations of human rights were committed during mining and commercialization and that money derived from sales did not support armed conflict. The fossil has an authenticated paper trail, including export permits from Myanmar. All documentation is available from the Peretti Museum Foundation upon request.

Credit: 
Florida Museum of Natural History

Toxin-adapted fish pass down epigenetic mutations to freshwater offspring

image: Poecilia mexicana fish also known as Atlantic molly

Image: 
Michael Tobler

PULLMAN, Wash. - You can take a fish out of toxic water, but its epigenetic mutations will remain for at least two generations.

A research team led by Washington State University scientists analyzed the epigenetics--molecular factors and processes that determine whether genes are turned on or off--of a group of Poecilia mexicana fish, or Atlantic molly, that live in springs naturally high in hydrogen sulfide, which is normally toxic to most organisms.

The researchers removed a sample of fish from the toxic water and bred them in freshwater. They found that the grandchildren of the sulfidic-adapted fish had more epigenetic marks in common with their wild, toxic-water-living grandparents than other Atlantic molly that had always lived in freshwater.

"After two generations in laboratory conditions, the fish generally retained their same epigenetic marks, which was really unexpected," said Joanna Kelley, WSU associate professor of evolutionary genomics and a corresponding author on the study published in Proceedings of the National Academy of Sciences. "In an evolutionary context, the study shows that these epigenetic marks are fairly stable."

Hydrogen sulfide is found in nature and as a by-product generated by many human activities, such as paper manufacturing, sewage treatment and gas exploration. For most animals, including humans, it is usually toxic at relatively low concentrations and fatal at high levels. Yet some populations of Atlantic molly have adapted to living in springs with high levels of hydrogen sulfide, while other groups of the same species have remained in freshwater. To Kelley and her colleagues, these fish presented a natural experiment to help address questions of how evolutionary adaptations occur.

For this study, Kelley collaborated with WSU environmental epigenetics and reproductive biologist Michael Skinner, to do the epigenetic analysis. The researchers raised a sample of sulfidic and non-sulfidic fish in freshwater environments. When the fish produced two generations of offspring, they measured their epigenetic similarities, specifically regions of DNA methylation, a type of chemical modification that can regulate gene expression, turning a gene on or off, without changing the DNA sequence string itself.

They found that the grand-offspring of the sulfidic fish had an 80% overlap in DNA methylation regions with the grandparent fish--even though they had been raised in freshwater. This compares to only 20% overlap with the non-sulfidic fish that had always lived in freshwater.

"It's really one of the first examples where we've taken an organism out of its normal environment and put it into a different environment and showed that the epigenetics keep being inherited going forward," said Skinner, also a corresponding author on the paper.

The study also adds to evidence from previous animal research showing that exposure to toxins has epigenetic effects that can last for generations. Skinner's lab has conducted studies on other wild species, including Darwin Finch in the Galapagos and the New Zealand mud snail as well as laboratory animals, showing that epigenetic changes resulting from environmental toxicants are passed down.

"This is not a one-off, unique species event. This has an impact on everything, including humans," said Skinner. "Although this is an animal model, it's a demonstration of how an environmental toxicant can actually shift the epigenetics, and it becomes programmed for subsequent generations."

Credit: 
Washington State University

Human microbiome could shed light on higher morbidity rate in minoritized populations

EVANSTON, Ill. --- The human gut is more than a source of instinct.

A new Northwestern University study is the first to explicitly address the gut microbiome as a pathway to understanding how environmental inequities could lead to health disparities.

Biological anthropologist Katherine Amato, assistant professor of anthropology at the Weinberg College of Arts and Sciences at Northwestern, is the study's lead author.

Amato says, despite a rich body of literature documenting environmental impacts on the microbiome, and the microbiome's impact on human health, the links between structural discrimination, altered environments, microbiome structure and health disparities have not been comprehensively outlined.

The new study calls for a better understanding of how structural discrimination that exposes minoritized populations to 'unhealthy' environments -- from altered diets, pollution, sanitation and lack of access to green space -- impacts the human gut microbiome, which in turn affects almost every aspect of human biology and health.

"Research has implicated the microbiome in most chronic diseases, and we know that there are disparities in most chronic diseases in which higher morbidity is observed in minoritized populations," Amato said.

Prior studies have demonstrated the impact of environmental inequality on health. For example, a 2020 study showed that children who are exposed to plants and dirt daily at school have higher microbial diversity and improved immune markers, likely because the exposure to microbes in these materials are transmitted to children's bodies. The pattern suggests that minoritized populations living in neighborhoods with little access to outdoor green space are more likely to have lower microbial diversity and associated health risks.

Among its many roles, the gut microbiome contributes to protection from pathogens, nutrition and metabolism, immune function, brain development and behavior. An altered gut microbiome can also have an impact on the gestational environment and the resulting health of the next generation.

Amato's study builds on prior research that shows the environment's role may be stronger than genetics in shaping the human microbiome, and that changes to the composition and function of the microbiome are most flexible in early life.

According to Amato, more empirical and interdisciplinary research is needed to facilitate epidemiological approaches that can tease apart multiple interacting determinants of health and help isolate the factors leading to chronic disease.

An ultimate goal of the research is to be able to deliver interventions that address environmental issues and individualized therapies to restore and improve microbiome health.

"Demonstrating the potential importance of these therapies in combatting health inequities could lead to transformative policy interventions that strive for universal access to emerging health technologies, and to healthcare more generally," Amato said.

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Northwestern University

'Ice' flavoured e-cig use may be linked to nicotine dependence among the young

The use of 'ice' flavoured e-cigarettes may be common and positively associated with conventional smoking and nicotine dependence among young adults, suggests research published online in the journal Tobacco Control.

And it's unclear where these' hybrid' vapes, combining fruit/sweet and cooling flavours, fit into current or future regulatory frameworks, which apply restrictions according to distinct flavour categories, point out the study authors.

'Ice' flavoured e-cigarettes--marketed as a combination of fruity/sweet and cooling flavours, such as 'blueberry ice' or 'melon ice'--recently entered the US market. Previous research suggests that young adult vapers prefer either fruit/sweet or menthol/mint flavours.

To try and gauge the appeal of these 'hybrid' vape flavours, and see if they might be linked to other behaviours around vaping and/or smoking among young adults, the study authors drew on 344 online survey responses submitted between May and August 2020.

The survey was part of the Happiness & Health Study--a prospective study of health behaviours which originally recruited 3396 ninth grade students in Los Angeles, California, in 2013.

The survey aimed to find out if respondents vaped and if so, which flavour they had used most often in the preceding 30 days: menthol/mint; fruit/sweet; or ice.

Respondents, whose average age was 21, were also asked if they smoked regular cigarettes, what symptoms of vaping dependency they had, and how often, and what type of vaping device they used.

Among the 407 ethnically diverse respondents who had vaped in the past 30 days, 383 provided information on flavours, but after excluding those who responded 'flavourless' or 'tobacco flavoured', the final analysis included 344 responses.

Overall, 168 (49%) reported most often using ice flavours; 60 (17%) menthol/mint; and 116 (34%) fruit/sweet.

Compared with the vapers of menthol/mint flavoured e-cigarettes, those vaping ice flavoured e-cigarettes were more likely to report smoking regular cigarettes over the previous 30 days: 31.5% vs 22%.

Ice flavour vapers were also less likely than menthol/mint vapers to report using rechargeable devices and more likely than fruit/sweet flavour users to use disposable non-cartridge devices: 65% vs 35%.

Disposable e-cigarettes are among the fastest growing segments of the e-cigarette market, note the study authors.

Ice flavour vapers were more likely to report symptoms of vaping dependence than fruit/sweet flavour vapers (67% vs 43%), to have started vaping during high school (74% vs 65%), and to report more daily vaping episodes: around 11 vs 8.

And they were also more likely than fruit/sweet or menthol/mint flavour vapers to report more vaping days over the past month: average 17 vs 12.

The study authors point out that their research relied on recall and didn't measure nicotine intake nor did it differentiate between e-cigarettes containing nicotine and those that didn't.

"While causality cannot be inferred from this cross sectional study," they caution, "it is possible that exposure to e-cigarettes in ice flavours may somehow increase nicotine vaping frequency and dependence," they add.

"Previous clinical laboratory studies show that fruit and menthol flavours each independently increase the appeal of e-cigarettes and suppress the aversive qualities of nicotine in young adults by creating perceptions of sweetness and coolness, respectively," they explain.

"Because ice flavours represent a hybrid that may contain both cooling and fruity flavouring constituents, it is unclear how these flavours fit into current and future regulatory policies that place differential restrictions across different flavour categories," they highlight.

"Further studies of the specific cooling agents and chemical constituents in ice flavoured products and the health effects of ice flavoured e-cigarette use are warranted," they conclude.

Credit: 
BMJ Group

Novel radiopharmaceutical tracks 'master switch' protein responsible for cancer growth

image: Clinical evaluation of [18F]DASA-23. A. Whole body PET maximum-intensity-projection images at different time points after [18F]DASA-23 administration in a healthy volunteer. B. Representative axial [18F]DASA-23 PET images of a healthy human brain at various summed time points post tracer administration. C. Representative 30-60 minute summed [18F]DASA-23 PET images in patients with intracranial malignancies. Standardized uptake values (SUV) and tumor-to-brain (TBR) values are shown.

Image: 
Image created by C Beinat et. al, Stanford University, Stanford, CA.

Reston, VA (Embargoed until 7:30 p.m. EDT, Monday, June 14, 2021)--A protein that is critical in cancer cell metabolism has been imaged for the first time with a newly developed radiopharmaceutical, 18F-DASA-23. Imaging with this novel agent has the potential to improve the assessment of treatment response for patients, specifically those with brain tumors. This study was presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting.

Tumor cells go through various changes to survive and prosper in the body. One of the key changes they make is modifying a master switch, known as pyruvate kinase M2 (PKM2). PKM2 controls cell metabolism and allows the cell to make more of the building blocks necessary for cell division.

"Until now we've had no way to assess the presence or activity levels of the PKM2 protein involved in that switch," said Corinne Beinat, PhD, instructor of radiology in the Radiology/Molecular Imaging Program at Stanford University in Stanford, California. "Through the development of 18F-DASA-23, this is the first time we can noninvasively interrogate the biochemistry of a tumor with respect to this master switch PKM2."

The study focused on patients with glioblastoma brain tumors, as normal brain cells have very low levels of PKM2. Healthy volunteers and patients with glioblastoma underwent positron emission tomography/magnetic resonance imaging with 18F-DASA-23. The radiopharmaceutical was successful in visualizing PKM2 in glioblastoma patients, while it was rapidly cleared from the bodies of healthy volunteers.

"This radiopharmaceutical can be very beneficial in assessing whether brain tumor treatments are working," stated Beinat. "For example, if a brain tumor is treated with a drug and then imaged with 18F-DASA-23, we can potentially know very quickly whether the therapeutic approach is working. If it's not effective, we won't have to waste more time waiting to see if the tumor itself is shrinking."

She added that 18F-DASA-23 could also possibly be used in other cancers or to learn more about how normal tissues adjust their metabolism during development or in response to varied environmental conditions.

Abstract 99. "Initial Clinical Evaluation of [18F]DASA-23, a PET Imaging Tracer for Evaluation of Aberrantly Expressed Pyruvate Kinase M2 in Glioblastoma," Corinne Beinat, Chirag Patel, Tom Haywood, Lewis Naya, Jessa Castillo, Bin Shen, Tarik Massoud, Andrei Iagaru, Guido Davidzon, Lawrence Recht and Sanjiv Gambhir, Stanford University, Stanford, California.

Credit: 
Society of Nuclear Medicine and Molecular Imaging

Lipophilic statin use linked to increased risk of dementia

image: Significant metabolic decline in the posterior cingulate cortex in lipophilic statin users after five to six years (top) compared to hydrophilic statin users and non-statin users (bottom).

Image: 
Image created by Prasanna Padmanabham and Daniel Silverman, UCLA

Reston, VA (Embargoed until 7:30 p.m. EDT, Monday, June 14, 2021)--In patients with mild cognitive impairment, taking lipophilic statins more than doubles their risk of developing dementia compared to those who do not take statins. According to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting, positron emission tomography (PET) scans of lipophilic statin users revealed a highly significant decline in metabolism in the area of the brain that is first impacted by Alzheimer's disease.

Statins are medications used to lower cholesterol and reduce the risk of heart attack or stroke. They are the most commonly used drugs in the developed world, and nearly 50 percent of Americans over age 75 use a statin. Different types of statins are available based on a patient's health needs, including hydrophilic statins that focus on the liver and lipophilic statins that are distributed to tissues throughout the body.

"There have been many conflicting studies on the effects of statin drugs on cognition," said Prasanna Padmanabham, project head, statins and cognition in the molecular and medical pharmacology student research program at the University of California, Los Angeles in Los Angeles, California. "While some claim that satins protect users against dementia, others assert that they accelerate the development of dementia. Our study aimed to clarify the relationship between statin use and subject's long-term cognitive trajectory."

Researchers separated study participants into groups based on three parameters: baseline cognitive status, baseline cholesterol levels and type of statin used. Participants underwent 18F-FDG PET imaging to identify any regions of declining cerebral metabolism within each statin group. Eight years of subject clinical data was analyzed.

Patients with mild cognitive impairment or normal cognition who used lipophilic statins were found to have more than double the risk of developing dementia compared to statin non-users. Over time, PET imaging of lipophilic statin users also showed a substantial decline in metabolism in the posterior cingulate cortex, the region of the brain known to decline the most significantly in the earliest stages of Alzheimer's disease. In contrast, no clinical or metabolic decline was found for users of other statins or for statin users with higher baseline serum cholesterol levels.

"By characterizing the metabolic effects associated with statin use, we are providing a new application of PET to further our understanding of the relationship between one of the most commonly used classes of drugs and one of the most common afflictions of the aging brain," noted Padmanabham. "Findings from these scans could be used to inform patients' decisions regarding which statin would be most optimal to use with respect to preservation of their cognition and ability to function independently."

Abstract 102. "Lipophilic Statins in Subjects with Early Mild Cognitive Impairment: Associations with Conversion to Dementia and Decline in Posterior Cingulate Brain Metabolism in a Long-term Prospective Longitudinal Multi-Center Study," Prasanna Padmanabham, Stephen Liu and Daniel Silverman, University of California, Los Angeles, Los Angeles, California.

Credit: 
Society of Nuclear Medicine and Molecular Imaging

Domesticated foxes display increased size in brain regions

image: Fox bred for dog-like behavior towards humans.

Image: 
Jennifer Johnson, Darya Shepeleva, and Anna Kukekova

When Erin Hecht was earning her Ph.D. in neuroscience more than a decade ago, she watched a nature special on the Russian farm-fox experiment, one of the best-known studies on animal domestication.

The study, running since 1958, tries to replicate the natural domestication of wolves to dogs by selectively breeding two strains of silver foxes so they exhibit certain behaviors. Scientists breed one to be tame and display dog-like behaviors with people, such as licking and tail wagging. The other is bred to react with defensive aggression when faced with human contact, while a third strain acts as the control and isn't bred for any specific behaviors.

Hecht, who's now an assistant professor in the Harvard Department of Human Evolutionary Biology, was fascinated by the experiment, which has helped scientists closely analyze the effects of domestication on genetics and behavior. But, she also thought something was missing.

"In that TV show, there was nothing about the brain," Hecht said. "I thought it was kind of crazy that there's this perfect opportunity to be studying how changes in brain anatomy are related to changes in the genome and changes in behavior, but nobody was really doing it yet."

Hecht acted fast and sent an email to Lyudmila N. Trut, the scientist running the Siberian institute where the Russian foxes were being studied. Fast forward to today and that email was foundational for a new study reporting on the surprising brain changes that occur in the Russian fox-farm experiment. Published Monday in the journal JNeurosci, the paper raises questions about some of the leading theories on domesticated animals' brains.

By analyzing MRI scans of the foxes, Hecht and her colleagues showed that both the foxes bred to be tame and those bred for aggression have larger brains and more grey matter than the brain of the control group (the foxes not bred for any particular behavior). These findings run in contrast to studies on chickens, sheep, cats, dogs, horses, and other animals that have shown domesticated species have smaller brains with less grey matter, than their wild forebears.

The team of researchers from Harvard, University of Illinois at Urbana-Champaign, Emory University, Cornell University, and the Russian Institute of Cytology and Genetics, explain the increase in size and grey matter, but can't yet be sure why this happens without further study. Their leading hypothesis centers on how the tame and aggressive strain have both been bred for specific behaviors at an accelerated time frame than many other domesticated animals. Dogs, for example, have been domesticated for at least 15,000 years.

"Both the tame and aggressive strains have been subject to intense, sustained selection on behavior, while the conventional strain undergoes no such intentional selection," they wrote. "Thus, it is possible that fast evolution of behavior, at least initially, may generally proceed via increases in grey matter."

As they analyzed the MRI scans, the research team noticed another surprise: similarities in the ways that the brains of the aggressive and tame foxes were changing. Both, for instance, showed enlargement in many of the same grey matter regions, including the prefrontal cortex, the amygdala, the hippocampus, and the cerebellum. This was despite the foxes being bred for opposite behaviors.

Results suggest that selection for opposite behavioral responses, in this case tame-versus-aggressive behavior, can produce similar changes in brain anatomy. The findings also suggest that significant changes to the structure and organization of the nervous system can evolve very quickly. In fact, it can happen within the span of less than a hundred generations.

Taken together, the researchers say the study's findings suggest existing ideas of brain changes in domestication may need revising, and that the brains of other animals, including humans, may have gone through similarly abrupt morphological shifts during times a sudden selection on behavior (rapid changes in environment or climate) occurred.

Next steps in the research include observing the foxes' brains scans at a cellular level.

The researchers believe there's a lot left to be learned from the Russian farm foxes and domesticated species, in general. That's because when a species splits from its wild counterpart, its brain, body, and behavior undergo rapid changes. Studying the foxes and other domesticated animals provides a window into these complex evolutionary processes.

"It's a more simple and straightforward way to see how evolution changes brains than we can achieve with just studying naturally occurring evolved brain changes," Hecht said.

Credit: 
Harvard University

USC study reveals potential new treatment target for Alzheimer's disease

image: Activation of cyclophilin A (CypA; red upper panels) leads to activation of MMP9 (red lower panels) in CD13+-pericytes (green) in brain capillaries of APOE4 humanized Alzheimer's disease (AD) mice with advanced amyloid-beta pathology. The images on the right, perpendicular to those on the left, show an overlap of of CypA or MMP9 with CD13+-pericytes: bar, 10 μm. Lectin+-endothelium is labeled blue indicating cortical capillaries.

Image: 
Angeliki Nikolakopoulou, PhD

Like amyloid plaque, the genetic variant APOE4 has long been associated with Alzheimer's disease, but still little is known about the role the gene plays in the disease process.

Now, a new study published in Nature Aging not only sheds light on how the gene may instigate a cascade of pathologies that contribute to Alzheimer's disease, but also suggests a new treatment target that might help people who carry the APOE4 gene in early and late stages of the disease. Keck School of Medicine of USC researchers found that APOE4 is associated with the activation of an inflammatory protein that causes a breakdown in the blood-brain barrier which protects the brain.

This research builds on a recent USC study that revealed APOE4 triggers leaks in the blood-brain barrier in humans, which lets toxic substances from the blood stream into the brain, damaging brain cells and disrupting cognitive functions. This process causes memory problems in patients whether or not their brain shows signs of amyloid-β, the sticky plaque peptide considered a hallmark of the disease.

The latest findings also suggest a new potential treatment to slow down or prevent the cognitive decline associated with Alzheimer's disease in patients with the APOE4 gene, independently of amyloid-β pathology.

"We're further focusing on therapeutics targets in blood vessels that could bring innovative treatments to people suffering from Alzheimer's disease, both early and late stages of the disease. Current findings in mouse models might be particularly promising for treating late stage disease in the presence of advanced amyloid-β pathology," said Berislav Zlokovic, MD, PhD, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC.

The role of APOE4, pericytes and Cyclophilin A in Alzheimer's disease

APOE4 has been shown to accelerate the blood-brain barrier breakdown by damaging pericytes, a layer of cells that strengthen and protect the brain capillaries which make up the blood-brain barrier. This breakdown is also associated with higher levels of Cyclophilin A, a pro-inflammatory protein, in the brain vessels of Alzheimer's disease patients with the APOE4 gene.

In this study, USC researchers focused on Cyclophilin A in mice with the APOE4 gene, which carries a high risk for Alzheimer's disease, and mice with the APOE3 gene, which carries an average risk for Alzheimer's disease. Cyclophilin A is found in pericytes and controls how strong the blood vessels are in maintaining the integrity of the blood-brain barrier. In the APOE4 mice, researchers found Cyclophilin A caused an enzyme that degrades blood vessels in the blood-brain barrier -- matrix metalloproteinase 9 (MMP9) -- to become active. This did not happen in the APOE3 gene mice.

Researchers then tried treating APOE4 mice with an inhibitor known to suppress Cyclophilin A. The inhibitor not only improved integrity in the blood-brain barrier in APOE4 mice, but also prevented development of further neuron loss and behavioral deficits. Researchers observed that the APOE4 mice treated with the inhibitor did not exhibit behavioral deficits during daily activities. This suggests that treatment targeting this pathway might have the potential to also slow down the progression of vascular and neurodegenerative disorders in people with Alzheimer's disease who have the APOE4 gene.

"So far there has been little hope for those in the late stage of the disease, which is very hard on patients and their loved ones," said Zlokovic. "We are excited to further study the potential that interventions focused on blood-brain barrier repair and blood vessel strength, independent of amyloid pathology, could have on slowing down or stopping neurodegeneration and cognitive decline in advanced Alzheimer's disease."

The inhibitor used in this study to suppress the Cyclophilin A, Debio-025, has been used in humans to treat hepatitis C, suggesting this could be a potential treatment for cognitive impairment in APOE4 carriers that show Cyclophilin A-MMP9 pathway activity in early or late disease stages.

Credit: 
Keck School of Medicine of USC

One step towards a daily-use deep UV light source for sterilization and disinfection

image: Schematic of GaN monolithic microcavity Second-Harmonic Generation (SHG) device on a Si pedestal structure.

Image: 
Osaka University

Osaka, Japan - Researchers from the Graduate School of Engineering and the Center for Quantum Information and Quantum Biology at Osaka University unveiled a new solid state second-harmonic generation (SHG) device that converts infrared radiation into blue light. This work may lead to a practical daily-use deep ultraviolet light source for sterilization and disinfection.

Recently, deep ultraviolet (DUV) light sources have been attracting much attention in sterilization and disinfection. In order to realize a bactericidal effect while ensuring user safety, a wavelength range of 220-230 nm is desirable. But DUV light sources in this wavelength range that are both durable and highly efficient have not yet been developed. Although wavelength conversion devices are promising candidates, conventional ferroelectric wavelength conversion materials cannot be applied to DUV devices due to absorption edge.

Since nitride semiconductors such as gallium nitride and aluminum nitride have relatively high optical nonlinearity, they can be applied to wavelength conversion devices. Due to its transparency to 210 nm, aluminum nitride is particularly suitable for DUV wavelength conversion devices. However, realizing structures with periodically inverted polarity like conventional ferroelectric wavelength conversion devices has proven quite difficult.

The researchers proposed a novel monolithic microcavity wavelength conversion device without a polarity-inverted structure. A fundamental wave is enhanced significantly in the microcavity with two distributed Bragg reflectors (DBR), and counter-propagating second harmonic waves are efficiently emitted in phase from the one side. As the first step towards a practical DUV light source, a gallium nitride microcavity device was fabricated via microfabrication technology, including dry etching and anisotropic wet etching for vertical and smooth DBR sidewalls. By obtaining a blue SH wave, the effectiveness of the proposed concept was successfully demonstrated.

"Our device can be adapted to use a broader range of materials. They can be applied to deep ultraviolet light emission or even broadband photon pair generation," senior author Masahiro Uemukai says. The researchers hope that because this approach does not rely on materials or periodically inverted structures, it will make future nonlinear optical devices easier to construct.

Credit: 
Osaka University

NUS study: Too many forewing eyespots is bad for butterflies

image: NUS doctoral student Ms V Gowri (left) and Research Fellow Dr Ian Chan (right) are part of the research team led by Professor Antónia Monteiro that observed the eyespots on bush brown butterflies.

Image: 
National University of Singapore

Singapore, 14 June 2021 - Many butterfly species bear distinct circular markings known as eyespots on their wings, and the functions of these rings of contrasting colours vary. A long-standing theory is that they serve as anti-predator defences - small eyespots along the wing margin can protect butterflies by directing predators to attack less important parts of the body, such as the hindwings, enabling them to escape.

Most nymphalid family butterflies have half as many eyespots on their forewings compared to their hindwings. In particular, this has been observed in the bush brown butterfly Bicyclus anynana.

A recent research by biologists from the National University of Singapore (NUS) sought to understand the impact of uneven distribution of eyespots. The team, led by Professor Antónia Monteiro from the NUS Department of Biological Sciences, found that the location of these eyespots is key to their protective function.

In their studies, the researchers found that variants of the bush brown butterfly which have more forewing eyespots suffered higher levels of predator attacks on these wings which are crucial for flight. This ultimately led to increased rates of successful predation, causing a decline in their population. The team also discovered that this variant laid fewer eggs due to its faster demise, and thereby had lower fitness, in evolutionary terms, than those with less forewing eyespots.

The findings were first published in the journal Proceedings of the Royal Society B on 26 May 2021.

Observing predator behaviour

In a set of predation experiments, the research team observed the behaviour of mantids in attacking two variants of bush brown butterflies with differing forewing eyespot numbers. Butterflies in the first group each had two forewing eyespots, while those in the other group had four. The results showed that the butterflies with two additional eyespots in the second group experienced more intense attacks to their forewings, in addition to the typical attacks on the hindwings.

"Butterflies can cope with damaged hindwings, but their forewings are critical for all stages of flight, from general flight to evasive manoevering. With more forewing damage, these butterflies are less likely to escape attacks and, even if they do, they would struggle to survive future attacks. From this experiment, it is clear the forewing with more eyespots becomes a more important target for predators," explained Dr Ian Chan, Research Fellow with the NUS Department of Biological Sciences, who was part of the research team.

To demonstrate the effects of the mantids' attacks on the butterflies, the researchers looked into three indicators of the butterflies' fitness: the amount of wing damage they suffered, the number of eggs laid, and lifespan. The team found that when compared to butterflies with fewer forewing eyespots, those with more eyespots received more damage to their forewings, laid fewer eggs, and had shorter lifespans.

Uncovering the mysteries of eyespot patterns

"Our findings demonstrate how the location of eyespots on butterfly wings both influences and is influenced by the behaviour of their predators, revealing more of the complexity behind how animals communicate to one another. Such a discovery raises further questions about why some species of butterflies have the opposite pattern, carrying more forewing than hindwing eyespots instead," said Professor Monteiro.

To deepen their understanding, the NUS researchers are looking to investigate whole predator-prey communities to uncover further drivers of eyespot number diversity in butterflies.

Credit: 
National University of Singapore