Culture

From schools of fish, to herds of antelope and even human societies, one of the group's many advantages is its inherent safety. Surrounded by their peers, individuals can lower their vigilance and calmly engage in other activities, such as foraging, or watching youtube videos.

But the Safety in Numbers rule has more to it than just being together. In many cases, communication also plays a big role. Social cues of danger are fairly well known. Just think about the different ways animals use to convey the presence of a threat. Shrieks, yelps and barks immediately come to mind.

Now, how about naming a few examples of social cues of safety? After all, knowing that the danger has passed is important for lowering one's defences and resuming other activities. The reason this task is more challenging is because it's actually a trick question - no social safety cues have been identified until now.

Remarkably, the discovery of the first social safety cue was made thanks to a tiny insect: the fruit fly. These results, published today (August 21st 2020) in the scientific journal Nature Communications, mark a new phase in our understanding of how social communication works.

A silent sign of danger

"When people think about social communication of danger, they normally think about alarm calls", says Marta Moita, a principal investigator at the Champalimaud Centre for the Unknown in Portugal. "But we are interested in a different type of threat cue, the expression of the defensive behaviours themselves."

Freezing is one of the three universal defence responses, together with fight and flight. This response is the best course of action in situations where escape is either impossible or less advantageous than just staying still with the hope of remaining unnoticed.

"Freezing may actually be a safer way of conveying the existence of danger to others", Moita points out. "This manner of social communication does not require the active production of a signal that may result in drawing unwelcome attention. Also, freezing may constitute a public cue that can be used by any surrounding animal regardless of species", she explains.

Moita's team has recently demonstrated that individual fruit flies freeze in response to an inescapable threat. This finding triggered their curiosity, would this behaviour change if there other flies were around?

Safety in (exactly how many) numbers

To answer this question, Clara Ferreira, the lead author of the study, proceeded with a systematic set of experiments, beginning with one fly, then two, three, and so forth, up to groups of ten.

"We placed the flies in a transparent closed chamber and repeatedly exposed them to an expanding dark disc, which mimics an object on a collision course. Just imagine the visual effect of an approaching open palm", Ferreira explains. "Many visual animals that are exposed to such a stimulus respond defensively, including humans. If they freeze, they often stay motionless for quite some time, even after the threat is gone."

Their results revealed that group size matters. "All groups - from two to ten - froze less than individual flies. However, we were surprised to find a complex effect of group size on the flies' behaviour", says Ferreira.

In groups of six and more, the flies froze transiently when the threat appeared and then resumed movement once it was gone. On the other hand, the flies' response pattern in groups of five or less was more similar to that of individual flies.

"Flies in those groups still froze less than single flies. However, their freezing time increased as the experiment progressed. The more repetitions of the threatening stimulus they experienced, the longer they would remain motionless when it reappeared", Ferreira explains. "These results were very intriguing", she adds. "This was the first time the effect of group size on freezing was systematically characterised in any species and it revealed a fascinating and intricate relation."

Should I stay or should I go?

These findings clearly demonstrated that flies change their defensive responses when others are present. This novel observation raised a pressing question - what social cues were the flies responding to? To find the answer, Ferreira and Moita meticulously analysed their previous results and conducted additional experiments using blind flies and controllable magnetic "dummy flies".

The results revealed a two-part answer. "The first part describes the flies' response to the appearance of the threat", Ferreira recounts. "We learned that an individual fly was more likely to enter freezing if its peers (magnetic or otherwise) froze in response to the threat. We were somewhat expecting to see this. Previous studies in the lab showed that in specific situations, freezing is a social cue of danger in rats. Here, we witnessed a similar behaviour in flies."

The second part of the answer, however, caught the researchers by surprise: flies were more likely to exit freezing if others began to move. "This means that flies were using the resumption of movement as a social cue of safety!", Ferreira points out.

"This is a completely novel phenomenon", Moita adds. "There are many types of recorded social alarm cues, but this is the first social safety cue to be identified in any animal species. It also pins down movement as the social cue we were searching for. In a sense, this cue 'kills two birds with one stone': the sudden cessation of movement signifies danger, whereas its resumption signifies safety."

Next stop - the brain

Moita and Ferreira's series of striking discoveries opens a unique opportunity to learn how the brain perceives and responds to social cues. "The fruit fly is one of the most powerful animal models used in scientific research nowadays", says Ferreira. "It offers specialised tools to study neurobiology in a very specific and targeted manner."

Indeed, the authors have already begun unraveling the neural basis of this behaviour. "In this project, we identified a set of visual neurons that are crucial for perceiving the movement of others as a safety cue", Ferreira explains. "And we are planning to continue investigating the neural circuits involved."

As Moita points out, even though flies and humans are different, there are parallels across these and other species that may make findings in the fly relevant for revealing general principles. "Since we are studying a fundamental behaviour spanning almost all of animal life - the tendency to seek safety in numbers - we believe that our work paves the way for understanding conserved mechanisms in other animals", she concludes.

CHICAGO (August 21, 2020): Computed tomography (CT) is used at a higher rate than ultrasound in children with developmental and cognitive impairments to diagnose appendicitis, even though CT scans increase radiation risk in smaller bodies. Additionally, these children have higher rates of postoperative emergency room visits and hospital readmissions after undergoing laparoscopic appendectomy (surgical removal of appendix) than children with normal development, according to new findings presented today by researchers at the American College of Surgeons (ACS) 2020 Quality and Safety Conference VIRTUAL.

Appendicitis is one of the most common causes of abdominal pain in children overall, as well as the most frequent surgical emergency in patients under age 18.*

In children with cognitive impairment, however, appendicitis is much more difficult to diagnose because they cannot communicate to us quite as easily as other children about their symptoms, so it makes the diagnosis more challenging, said study coauthor Robert Cina, MD, FACS, associate professor of surgery at the Medical University of South Carolina, Charleston.

The researchers used data from the ACS National Surgical Quality Improvement Program (ACS NSQIP®) database to evaluate the impact of cognitive impairment in the diagnosis and treatment of appendicitis in children. ACS NSQIP is a nationally validated, risk-adjusted, outcomes-based program designed to measure and improve the process of surgical care in participating hospitals.

The analysis involved 16,986 patients under age 18 who underwent laparoscopic appendectomy in 2018. Of these, 293 patients had developmental and cognitive impairments.

Outcomes comparisons showed that children with cognitive deficits were slightly younger (average age 10 versus 11) and had more CT scans performed than children without developmental delays (55 percent versus 41 percent).

"The disease severity is the same in both groups, yet to make a diagnosis, we are using CT scans at a higher rate, which requires the use of radiation instead of the ultrasound, which is what we advocate nowadays, especially in the pediatric population," said the study's lead author Raphael H. Parrado, MD, a general surgery resident at the Medical University of South Carolina.

CT scans shouldn't be automatically performed because there are long term risks of radiation. "Our exploratory study suggests that physicians are deciding to use CT scans over ultrasound initially," Dr. Cina said. "The reason may be that children who are neurologically impaired cannot tell us specifically about their symptoms, and as a result, they may be getting imaged more often to help make the diagnosis."

Another important finding is that while no differences were seen in postoperative complications, readmissions and postoperative emergency department visit rates were higher in children with cognitive impairment compared to neurologically normal children; readmissions: 8 percent versus 3 percent and emergency department visits: 13 percent versus 8 percent.

The study also found that length of stay was slightly longer in children with cognitive delay (average 2 days versus 1 day).

In theory, the rates should be the same because we are treating the same disease, Dr. Parrado said. "We're glad to bring attention to the huge differences in the care of these children. This study is showing for the first time what we are doing differently in this vulnerable population."

In addition, this study sheds light on other variables contributing to the differences in these pediatric groups. "We need to develop tailored communication tools and education for these children and their parents. Physicians should closely monitor these patients during diagnosis and follow up to make sure everything goes well," Dr. Parrado said.

The results of this study may help create a roadmap for diagnosing and treating appendicitis in these children.

"The takeaway from this research is that we are treating the children with the best of our ability, but there is still room for improvement," Dr. Cina said. "We see that there is some inequity in how this fragile patient population is undergoing imaging. But our study allows us to look at this issue in a deeper way to see how we can improve the outcome for these kids. We need to make sure that we use the same processes in making our diagnoses as we would for others in regard to radiation."

A limitation of the study is that it's a retrospective study, the researchers noted. More data points are needed to clarify the underlying reasons for the differences in outcomes.

Next, the researchers will explore the variables that have been highlighted in this study in order to develop an understanding as to why the differences exist and the best way to improve the care for these children.

New simulations show that NASA's Nancy Grace Roman Space Telescope will be able to reveal myriad rogue planets - freely floating bodies that drift through our galaxy untethered to a star. Studying these island worlds will help us understand more about how planetary systems form, evolve, and break apart.

Astronomers discovered planets beyond our solar system, known as exoplanets, in the 1990s. We quickly went from knowing of only our own planetary system to realizing that planets likely outnumber the hundreds of billions of stars in our galaxy. Now, a team of scientists is finding ways to improve our understanding of planet demographics by searching for rogue worlds.

"As our view of the universe has expanded, we've realized that our solar system may be unusual," said Samson Johnson, a graduate student at Ohio State University in Columbus who led the research effort. "Roman will help us learn more about how we fit in the cosmic scheme of things by studying rogue planets."

The findings, published in the Astronomical Journal, center on the Roman Space Telescope's ability to locate and characterize isolated planets. Astronomers have only tentatively discovered a few of these nomad worlds so far because they are so difficult to detect.

Finding galactic nomads

Roman will find rogue planets by conducting a large microlensing survey. Gravitational lensing is an observational effect that occurs because the presence of mass warps the fabric of space-time. The effect is extreme around very massive objects, like black holes and entire galaxies. Even solitary planets cause a detectable degree of warping, called microlensing.

If a rogue planet aligns closely with a more distant star from our vantage point, the star's light will bend as it travels through the curved space-time around the planet. The result is that the planet acts like a natural magnifying glass, amplifying light from the background star. Astronomers see the effect as a spike in the star's brightness as the star and planet come into alignment. Measuring how the spike changes over time reveals clues to the rogue planet's mass.

"The microlensing signal from a rogue planet only lasts between a few hours and a couple of days and then is gone forever," said co-author Matthew Penny, an assistant professor of physics and astronomy at Louisiana State University in Baton Rouge. "This makes them difficult to observe from Earth, even with multiple telescopes. Roman is a game-changer for rogue planet searches."

Microlensing offers the best way to systematically search for rogue planets - especially those with low masses. They don't shine like stars and are often very cool objects, emitting too little heat for infrared telescopes to see. These vagabond worlds are essentially invisible, but Roman will discover them indirectly thanks to their gravitational effects on the light of more distant stars.

Lessons from cosmic castaways

Johnson and co-authors showed that Roman will be able to detect rogue planets with masses as small as Mars. Studying these planets will help narrow down competing models of planetary formation.

The planet-building process can be chaotic, since smaller objects collide with one another and sometimes stick together to form larger bodies. It's similar to using a piece of playdough to pick up other pieces. But occasionally collisions and close encounters can be so violent that they fling a planet out of the gravitational grip of its parent star. Unless it manages to drag a moon along with it, the newly orphaned world is doomed to wander the galaxy alone.

Rogue planets may also form in isolation from clouds of gas and dust, similar to how stars grow. A small cloud of gas and dust could collapse to form a central planet instead of a star, with moons instead of planets surrounding it.

Roman will test planetary formation and evolution models that predict different numbers of these isolated worlds. Determining the abundance and masses of rogue planets will offer insight into the physics that drives their formation. The research team found that the mission will provide a rogue planet count that is at least 10 times more precise than current estimates, which range from tens of billions to trillions in our galaxy. These estimates mainly come from observations by ground-based telescopes.

Since Roman will observe above the atmosphere, nearly a million miles away from Earth in the direction opposite the Sun, it will yield far superior microlensing results. In addition to providing a sharper view, Roman's perspective will allow it to stare at the same patch of sky continuously for months at a time. Johnson and his colleagues showed that Roman's microlensing survey will detect hundreds of rogue planets, even though it will search only a relatively narrow strip of the galaxy.

Part of the study involved determining how to analyze the mission's future data to obtain a more accurate census. Scientists will be able to extrapolate from Roman's rogue planet count to estimate how common these objects are throughout the entire galaxy.

"The universe could be teeming with rogue planets and we wouldn't even know it," said Scott Gaudi, a professor of astronomy at Ohio State University and a co-author of the paper. "We would never find out without undertaking a thorough, space-based microlensing survey like Roman is going to do."

The Nancy Grace Roman Space Telescope is managed at Goddard, with participation by NASA's Jet Propulsion Laboratory and Caltech/IPAC in Pasadena, the Space Telescope Science Institute in Baltimore, and a science team comprising scientists from research institutions across the United States.

Nighttime imagery from NASA-NOAA's Suomi NPP satellite found the center of now Tropical Storm Genevieve moving along the coast of the Baja California, Mexico peninsula and further away from land. The storm is weakening rapidly from several factors. It is expected to be a remnant low-pressure area by Saturday, Aug. 21.

On Aug. 20, the government of Mexico has discontinued the Tropical Storm Warning for the west coast of the Baja California peninsula.

NASA's Night-Time View of Genevieve

Hurricane Genevieve weakened to a tropical storm and nighttime satellite imagery showed the structure of the storm had become more disorganized over the previous 24 hours. The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a nighttime image of Genevieve during the early morning hours of Aug. 20 at 4:14 a.m. EDT (0818 UTC). Nighttime imagery from NASA-NOAA's Suomi NPP satellite was created using the NASA Worldview application at NASA's Goddard Space Flight Center in Greenbelt, Md.

NOAA's National Hurricane Center (NHC) Senior Hurricane Specialist Stacy Stewart noted, "The combination of moderate southerly vertical wind shear, cooler sea-surface temperatures near 26 degrees Celsius (78.8 degrees Fahrenheit), and dry mid-level air has caused Genevieve to rapidly weaken over the past 24 hours.  Very little deep convection remains, and what convection there is has been displaced well to the northeast of the low-level center."

Genevieve's Status on Aug. 21

At 8 a.m. EDT (1500 UTC) on Aug. 21, the National Hurricane Center (NHC) noted the center of Tropical Storm Genevieve was located near latitude 24.6 degrees north and longitude 114.6 degrees west. That is about 145 miles (235 km) west of Cabo San Lazaro, Mexico.

Genevieve was moving toward the west-northwest near 9 mph (15 kph), and this general motion is expected to continue during the next few days. Maximum sustained winds have decreased to near 45 mph (75 kph) with higher gusts. The estimated minimum central pressure is 1001 millibars.

On the forecast track, the center of Genevieve will move farther away from the Baja California peninsula. Continued weakening is expected, and Genevieve is forecast to degenerate into a post-tropical cyclone later today.

NASA Hubble Space Telescope images of comet NEOWISE, taken on Aug. 8, zero in on the visitor's coma, the gossamer shell of gas and dust that surrounds its nucleus as it is heated by the Sun. This is the first time Hubble has photographed a comet of this brightness at such resolution after this close of a pass by the Sun.

The comet photos were taken after NEOWISE skimmed closest to the Sun on July 3, 2020, at a distance of 27 million miles (43 million kilometers). Other comets often break apart due to thermal and gravitational stresses at such close encounters, but Hubble's view shows that apparently NEOWISE's solid nucleus stayed intact.

"Hubble has far better resolution than we can get with any other telescope of this comet," said lead researcher Qicheng Zhang of Caltech in Pasadena, California. "That resolution is very key for seeing details very close to the nucleus. It lets us see changes in the dust right after it's stripped from that nucleus due to solar heat, sampling dust as close to the original properties of the comet as possible."

The heart of the comet, its icy nucleus, is too small to be seen by Hubble. The ball of ice may be no more than 3 miles (4.8 kilometers) across. Instead, the Hubble image captures a portion of the vast cloud of gas and dust enveloping the nucleus, which measures about 11,000 miles (18,000 kilometers) across in this photo. Hubble resolves a pair of jets from the nucleus shooting out in opposite directions. They emerge from the nucleus as cones of dust and gas, and then are curved into broader fan-like structures by the rotation of the nucleus. Jets are the result of ice sublimating beneath the surface with the resulting dust/gas being squeezed out at high velocity.

The Hubble photos may help reveal the color of the comet's dust and how those colors change as the comet moves away from the Sun. This, in turn, may explain how solar heat affects the composition and structure of that dust in the comet's coma. The ultimate goal here would be to learn the original properties of the dust to learn more about the conditions of the early solar system in which it formed.

Comet NEOWISE is considered the brightest comet visible from the Northern Hemisphere since 1997's Hale-Bopp. It's headed beyond the outer solar system, now traveling at a whopping 144,000 miles per hour. It will not return to the Sun for another nearly 7,000 years.

Researchers are currently delving more into the data to see what they're able to confirm.

NASA's Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) mission first discovered its namesake comet in March 2020. As the comet made its way closer to the Sun, searing heat melted its ices, unleashing dust and gas that leaves the signature tails. Throughout the summer, ground-based sky watchers in the Northern Hemisphere were able to catch a view of the traveler moving across the sky.

The NASA/ESA Hubble Space Telescope has captured the closest images yet of the sky’s latest visitor to make the headlines, comet C/2020 F3 NEOWISE, after it passed by the Sun. The new images of the comet were taken on 8 August and feature the visitor’s coma, the fine shell that surrounds its nucleus, and its dusty output.

Comet NEOWISE is the brightest comet visible from the Northern Hemisphere since 1997’s Hale-Bopp comet. It’s estimated to be travelling at over 60 kilometres per second. The comet’s closest approach to the Sun was on 3 July and it’s now heading back to the outer reaches of the Solar System, not to pass through our neighbourhood again for another 7000 years.

Hubble’s observation of NEOWISE is the first time a comet of this brightness has been photographed at such high resolution after its pass by the Sun. Earlier attempts to photograph other bright comets (such as comet ATLAS) proved unsuccessful as they disintegrated in the searing heat.

Comets often break apart due to thermal and gravitational stresses at such close encounters, but Hubble's view suggests that NEOWISE's solid nucleus stayed intact. This heart of the comet is too small to be seen directly by Hubble. The ball of ice may be no more than 4.8 kilometres across. But the Hubble image does captures a portion of the vast cloud of gas and dust enveloping the nucleus, which measures about 18 000 kilometres across in this image.

Hubble's observation also resolves a pair of jets from the nucleus shooting out in opposite directions. They emerge from the comet's core as cones of dust and gas, and then are curved into broader fan-like structures by the rotation of the nucleus. Jets are the result of ice sublimating beneath the surface with the resulting dust/gas being squeezed out at high velocity.

The Hubble photos may also help reveal the colour of the comet’s dust and how that colour changes as the comet moves away from the Sun. This, in turn, may explain how solar heat affects the contents and structure of that dust and the comet’s coma. The ultimate goal here would be to determine the original properties of the dust. Researchers who used Hubble to observe the comet are currently delving further into the data to see what they’re able to find.

Hubble has captured other well-known comet visitors throughout the past year. This includes snapping images of the breakup of comet ATLAS in April 2020 and impressive images of the interstellar comet 2I BORISOV in October 2019 and December 2019.

BOSTON - A new bioluminescent reporter that tracks DNA double stranded break (DSB) repair in cells has been developed by researchers from Massachusetts General Hospital (MGH) and the Academia Sinica in Taiwan. The international team's novel bioluminescent repair reporter (BLRR)-based system can be used to monitor DNA repair pathways directly in animals as well as cell lines. No such system previously existed for in vivo studies. These pathways play a crucial role in multiple conditions, including cancer.

"One of the main reasons cancer cells are resistant to treatment is that they can inherently repair the DNA damage caused by radiation and chemotherapy," explains Christian Elias Badr, PhD, investigator in the Department of Neurology at MGH and co-senior author of the paper. The study's other co-senior author is Charles Pin-Kuang Lai, PhD, at the Academia Sinica in Taiwan.

Their study appeared this month as an online advance paper in Nucleic Acids Research

DSB damage repair is key to maintaining genomic integrity and cell viability. It also plays a role in cancer treatment, which often includes chemoradiotherapy (radiation and chemotherapy), which disrupts DSB. A cell may recognize the damage and use its intrinsic DNA damage response (DDR) to reduce DSB-caused cell death. As a result, the cancer cell's own DNA repair mechanisms can promote drug resistance and recurrence in some malignancies. Researchers would like to know more about them.

The BLRR approach builds on earlier work members of the team did on enzymes called luciferases. These produce bioluminescence, making them useful for tracking molecules in cells. BLRR uses secreted Gaussia and Vargula luciferases to detect homology-directed repair (HDR) and non-homologous end joining (NHEJ) -- the two major pathways to DSB repair. Using BLRR. Researchers can track HDR and NHEJ-related activities over time in cells. It also detects DSB repairs in xenografted tumors in vivo.

"You can study DNA damage in cells with next generation sequencing (NGS), but that's more costly and time consuming," Badr says. "And our system's accuracy is comparable to NGS."

The researchers used their new tag to carry out multiple studies. In one, they found a significant difference in the efficiency of CRISPR/Cas9-mediated editing with guide RNAs 1-10bp apart. They also used BLRR analysis to detect altered dynamics for DSB repair induced by small molecule modulators. Lastly, they used the system to discover HDR-suppressing functions of anticancer cardiac glycosides in human glioblastomas and glioma cancer stem-like cells by inhibiting DNA repair protein RAD51 homolog 1.

In their paper, the authors describe the BLRR system as: "A highly sensitive platform to simultaneously and longitudinally track HDR and NHEJ dynamics that is sufficiently versatile for elucidating the physiology and therapeutic development of DSB repair." The authors plan on using this reporter system in high throughput drug screening to identify novel therapeutics that sensitize cancer cells to radiation and chemotherapy.

A new study of 27 patients hospitalized with COVID-19 has provided a detailed map of natural killer (NK) cell responses to SARS-CoV-2 infection, revealing that specific characteristics of NK cell activation associate with different levels of disease severity. The findings are consistent with previous reports that NK cells exist in lower frequencies in the blood of patients with COVID-19 compared with healthy controls, but also show that increased numbers of certain NK cell types - adaptive NK cells specifically - correlate with severe, but not moderate, disease. Compared with adaptive immune cell responses to SARS-CoV-2, much less is known about the quick-acting innate immune response to SARS-CoV-2 and how it influences the course of disease. NK cells are innate immune cells located in the blood and abundantly in the lungs, where they act not only as rapid responders to viral infection, but also as influencers of adaptive immune responses: depending on their levels of activation, the unique "adaptive NK cell" subset can help T cells either control infection or contribute to disease.

To investigate whether NK cells' virus-controlling roles extend to SARS-CoV-2, Christopher Maucourant and colleagues analyzed NK cells taken from the blood of 27 patients with either severe or moderate COVID-19 and 17 healthy controls. They observed that NK cells were severely reduced but strongly activated in the blood of patients with COVID-19 compared with controls. The "arming" of these activated NK cells with cytotoxic effector proteins correlated with the development of severe disease, the researchers found. An additional high-dimensional analysis showed that patients with severe - but not moderate - COVID-19 harbored higher numbers of adaptive NK cells than healthy controls. Adaptive NK cells are thought to arise with cytomegalovirus (CMV) infection and remain afterward to act against future viral infections; indeed, the researchers observed the expansion of adaptive NK cells only in CMV-seropositive individuals among the COVID-19 cohort. Based on their findings, Maucourant et al. suggest several directions for future work on the role of NK cells in COVID-19, including whether NK cell activation states identified in the blood can also be found in the lungs, and how NK cell responses vary at different time points during SARS-CoV-2 infection.

Programmable DNA nanoswitches that bind to viral RNA in human body fluids may provide an inexpensive platform to rapidly detect a wide variety of emerging viruses, including SARS-CoV-2, according to a new study. This approach may make testing more manageable in resource-limited areas, since it does not require enzymes or significant laboratory infrastructure, only costs about 1 penny per reaction, and can be performed within hours. RNA viruses are often the culprits behind widespread outbreaks, since their high mutation rates enable them to evolve quickly. Detecting these emergent RNA viruses remains challenging, especially in impoverished areas, since detection time windows can be as short as just a few days and laboratories may not be equipped to conduct immunoglobulin blood tests, which remain standard for clinical testing but sometimes lead to false positive results. To help overcome these challenges, Zhou et al. developed DNA nanoswitches that bind to both ends of target viral RNAs, forming loop-shaped compounds.

These negatively-charged, RNA-containing nanoswitch loops are then placed in a gel and stimulated with an electrical current, pulling them towards a positive electrode on the other end of the gel. Since the nanoswitches move more slowly when they are bound to viral RNA, this gel electrophoresis technique reveals the virus' presence. The researchers first tested this approach with DNA nanoswitches designed to target a sequence in the Zika virus genome and demonstrated its ability to detect clinically-relevant levels of Zika RNA in human urine. Zhou et al. next developed nanoswitches to target SARS-CoV-2 RNA in human saliva, finding that they could successfully detect the virus' presence within about 2 hours. The nanoswitches also successfully differentiated between Zika virus and Dengue virus, which occur in overlapping geographical regions and cause similar symptoms, demonstrating the nanoswitches' potential to avoid misdiagnoses.

Scientists at Washington University School of Medicine in St. Louis have developed a vaccine that targets the SARS-CoV-2 virus, can be given in one dose via the nose and is effective in preventing infection in mice susceptible to the novel coronavirus. The investigators next plan to test the vaccine in nonhuman primates and humans to see if it is safe and effective in preventing COVID-19 infection.

The study is available online in the journal Cell.

Unlike other COVID-19 vaccines in development, this one is delivered via the nose, often the initial site of infection. In the new study, the researchers found that the nasal delivery route created a strong immune response throughout the body, but it was particularly effective in the nose and respiratory tract, preventing the infection from taking hold in the body.

"We were happily surprised to see a strong immune response in the cells of the inner lining of the nose and upper airway -- and a profound protection from infection with this virus," said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. "These mice were well protected from disease. And in some of the mice, we saw evidence of sterilizing immunity, where there is no sign of infection whatsoever after the mouse is challenged with the virus."

To develop the vaccine, the researchers inserted the virus' spike protein, which coronavirus uses to invade cells, inside another virus - called an adenovirus - that causes the common cold. But the scientists tweaked the adenovirus, rendering it unable to cause illness. The harmless adenovirus carries the spike protein into the nose, enabling the body to mount an immune defense against the SARS-CoV-2 virus without becoming sick. In another innovation beyond nasal delivery, the new vaccine incorporates two mutations into the spike protein that stabilize it in a specific shape that is most conducive to forming antibodies against it.

"Adenoviruses are the basis for many investigational vaccines for COVID-19 and other infectious diseases, such as Ebola virus and tuberculosis, and they have good safety and efficacy records, but not much research has been done with nasal delivery of these vaccines," said co-senior author David T. Curiel, MD, PhD, the Distinguished Professor of Radiation Oncology. "All of the other adenovirus vaccines in development for COVID-19 are delivered by injection into the arm or thigh muscle. The nose is a novel route, so our results are surprising and promising. It's also important that a single dose produced such a robust immune response. Vaccines that require two doses for full protection are less effective because some people, for various reasons, never receive the second dose."

Although there is an influenza vaccine called FluMist that is delivered through the nose, it uses a weakened form of the live influenza virus and can't be administered to certain groups, including those whose immune systems are compromised by illnesses such as cancer, HIV and diabetes. In contrast, the new COVID-19 intranasal vaccine in this study does not use a live virus capable of replication, presumably making it safer.

The researchers compared this vaccine administered to the mice in two ways -- in the nose and through intramuscular injection. While the injection induced an immune response that prevented pneumonia, it did not prevent infection in the nose and lungs. Such a vaccine might reduce the severity of COVID-19, but it would not totally block infection or prevent infected individuals from spreading the virus. In contrast, the nasal delivery route prevented infection in both the upper and lower respiratory tract -- the nose and lungs -- suggesting that vaccinated individuals would not spread the virus or develop infections elsewhere in the body.

The researchers said the study is promising but cautioned that the vaccine so far has only been studied in mice.

"We will soon begin a study to test this intranasal vaccine in nonhuman primates with a plan to move into human clinical trials as quickly as we can," Diamond said. "We're optimistic, but this needs to continue going through the proper evaluation pipelines. In these mouse models, the vaccine is highly protective. We're looking forward to beginning the next round of studies and ultimately testing it in people to see if we can induce the type of protective immunity that we think not only will prevent infection but also curb pandemic transmission of this virus."

Boston - A new study shows that nephrologists do not always agree on their interpretation of images from urine sediment tests, which are frequently ordered to evaluate a variety of kidney diseases. Led by researchers at Boston Medical Center and published in JAMA Network Open, the findings indicate the need to standardize education and training around evaluating urine sediment tests to improve the test's reliability, and help prevent misinterpretation and potential patient harm.

Millions of urine sediment microscopy tests are conducted each year in the United States to diagnose conditions such as urinary tract infections and kidney diseases. The results of these tests are often used to make treatment decisions, such as whether it's necessary to conduct a kidney biopsy or use immunosuppressive medications to treat a patient. While the urine sediment examination has been widely used for decades, there have been few studies looking at the validity of the test or on the variability among nephrologists in their interpretation of the urine sediment test results.

"The urine sediment exam has played a fundamental role in taking care of patients with known or suspected kidney diseases - it's important to ensure that the tests are being interpreted appropriately," said Sushrut S. Waikar, MD, chief of the section of nephrology at Boston Medical Center and the study's corresponding author. The study team prospectively collected urine samples from adult participants who were undergoing a kidney biopsy at Brigham and Women's Hospital in Boston while Waikar was serving as director of Renal Ambulatory Services at the Brigham. During evaluation of the urine sediment through a microscope, the researchers collected high-resolution images and videos that were used during the analysis. These images and videos were distributed to 14 highly experienced nephrologists at teaching hospitals across the United States. The nephrologists were shown the same images and videos, and asked to identify features in the urine sediment and to provide a single suspected diagnosis based on the urine sediment findings.

The nephrologists disagreed with one another on several important urine sediment findings. The interobserver reliability - based on differences in responses from the nephrologists - ranged from moderate to substantial. For example, important findings, such as white blood cell casts and red blood cell casts - which can indicate serious kidney diseases - were often interpreted differently across nephrologists. Other findings, such as granular casts, showed higher levels of agreement.

"Ideally, the interpretation of the urine sediment should be the same when done by different doctors," added Waikar, who also is the Norman G. Levinsky Professor of Medicine at Boston University School of Medicine. "Our study provides important information that can be used to address these variabilities in order to create a better, more reliable test."

The study authors note that, while doctors don't always agree, it's important to develop standardized training to teach doctors how to interpret urine sediment tests, ideally with a library of high resolution images and videos from patient samples. They also suggested the potential role for artificial intelligence approaches for image analysis to aid physicians with interpretation of this time-honored test in clinical medicine.

This study was funded in part by the National Institutes of Diabetes, Digestive, and Kidney Diseases.

Researchers may have come one step closer toward understanding how the immune system contributes to severe COVID-19. In a study published in Science Immunology, researchers at Karolinska Institutet in Sweden show that so-called natural killer (NK) cells were strongly activated early after SARS-CoV-2 infection but that the type of activation differed in patients with moderate and severe COVID-19. The discovery contributes to our understanding of development of hyperinflammation in some patients.

SARS-CoV-2 infection can in some cases cause severe COVID-19 disease. Although this is thought to be partially driven by a misdirected innate immune response, many aspects of the early immune response to the infection remain elusive.

Researchers at Karolinska Institutet have now, in collaboration with colleagues at the Karolinska University Hospital, investigated the early response to SARS-CoV-2 infection of NK cells, a cell type in the immune system known to be important in the control of viral infections.

The study analyzed blood samples from 27 patients with moderate (10) and severe (17) COVID-19 infection. The researchers also included blood samples from 17 healthy individuals as a control group. The result showed that NK cells were strongly activated in the blood shortly after infection.

"The type of NK cell activation detected differed considerably in patients with moderate compared to severe disease," says Niklas Björkström, physician and immunology researcher at the Center for Infectious Medicine, Department of Medicine Huddinge, at Karolinska Institutet, who led the study.

It is likely that the type of NK cell response observed in SARS-CoV-2 infected patients with moderate disease is a canonical NK cell response shared between many types of viral infections, according to the researchers.

However, patients who developed severe COVID-19 had a different composition of responding NK cells. These patients' NK cells generally had higher expression of the proteins perforin, NKG2C and Ksp37, which according to the researchers reflect a high presence of so-called adaptive NK cells. Adaptive NK cells have an even greater ability to kill target cells compared to other NK cells.

The researchers are now investigating to what extent the NK cell-mediated immune response observed in the critically ill patients might contribute to COVID-19 severity, and the extent to which other parts of the response may be beneficial.

"Taken together, our findings provide additional insights into immune reactions in early SARS-CoV-2 infection and ensuing COVID-19 disease," Niklas Björkström says. "We hope that these insights will contribute to the improved care and treatment of patients with severe COVID-19 disease."

The study is part of the larger Karolinska COVID-19 Immune Atlas project, which aims to increase knowledge about the characteristics of immune cells in patients with COVID-19.

BEER-SHEVA, Israel, August 21, 2020 - A new peer-reviewed study published in Science Advances confirms the success of a new COVID-19 pooling test that identifies all positive subjects, including asymptomatic carriers, in a single round of testing.

P-BEST, an algorithmic method for pooling-based efficient SARS-CoV-2 testing, was developed by a group of researchers from Ben-Gurion University of the Negev (BGU), the National Institute for Biotechnology in the Negev (NIBN), The Open University of Israel (OUI) and Soroka University Medical Center. Click here for the video about P-BEST.

"Approximately 10-30% of COVID-19 infected patients are asymptomatic and significant viral spread can occur days before symptom onset," says Prof. Angel Porgador, BGU deputy vice president of research and development and member of the NIBN. "Until there is a vaccine, there will be an urgent need to increase diagnostic testing capabilities to allow for screening of asymptomatic and pre-symptomatic populations. This new single stage diagnostic test will help prevent the spread of the disease by identifying these patients sooner and at a lower cost using significantly fewer tests."

In the current study, 384 samples were divided into only 48 pools providing an eightfold increase in testing efficiency and similar reduction in testing costs for reagents. Each pool comprises a unique set of 48 samples, where each sample appears in exactly six pools using a specific combinatorial design. These 48 pools were then tested at the Soroka virology laboratory using a COVID-19 PCR-based diagnostic protocol that included an RNA extraction stage. After testing each of the 48 pools individually, the researchers successfully identified up to five positive carriers within the 384 samples, without having to test the subjects in that pool.

"P-BEST can be configured on the basis of the carrier rate," says Dr. Noam Shental, head of the OUI Computer Science Division. "The lower the carrier rate, the higher efficiency. Our pooling method has been tested using an advanced liquid-handling robotic system that can perform the task in an hour and can be performed in a typical clinical diagnostic laboratory anywhere in the world."

The researchers also tested the performance of P-BEST in a clinical study aimed at screening asymptomatic and mildly symptomatic healthcare workers. In the study, they screened 1,115 asymptomatic health care personnel at Soroka using P-BEST. Subjects were recruited across all Soroka staff and included physicians, nurses, nurse assistants, as well as clinical and administrative staff.

A total of 296 (26.5%) subjects worked in direct contact with patients with COVID-19. Within the cohort, 926 (93.1%) subjects reported themselves as totally asymptomatic, 71 (6.3%) reported a mild cough, and 70 (6.3%) reported rhinorrhea. The 1,115 participants were tested using only 144 tests. All of the pools tested were negative. Because of the decreasing carrier rates in Israel during April 2020, the third batch was blindly spiked with a sample from a patient with COVID-19, which was positively identified.

"P-BEST is ideal for conducting carrier screening when infection rates are very low, less than one percent," says Prof. Tomer Hertz from BGU's Shraga Segal Department of Microbiology, Immunology and Genetics. "This will provide significant savings in reagents and other diagnostic testing resources while significantly increasing testing capacity."

BGU and OUI have established a company, Poold Diagnostics, to pursue large scale COVID-19 testing, following the clinical study. In mid-August, the Israel Ministry of Health approved the use of P-BEST in clinical laboratories in the State of Israel.

"The BGU research team has validated a pooling method that will allow sizeable populations in Israel and ultimately other countries to be tested accurately and at low cost for COVID-19," says Doug Seserman, chief executive officer of the New York City-based AABGU. "The BGU COVID-19 Response Effort is moving forward on commercializing a number of technologies and innovations to mitigate effects of this pandemic."

ORLANDO, August 21, 2020 - University of Central Florida researchers are making the cutting-edge field of attosecond science more accessible to researchers from all disciplines.

Their method to help open up the field is detailed in a new study published today in the journal Science Advances.

An attosecond is one billionth of a billionth of a second, and the ability to make measurements with attosecond precision allows researchers to study the fast motion of electrons inside atoms and molecules at their natural time scale.

Measuring this fast motion can help researchers understand fundamental aspects of how light interacts with matter, which can inform efforts to harvest solar energy for power generation, detect chemical and biological weapons, perform medical diagnostics and more.

"One of the main challenges of attosecond science is that it relies on world-class laser facilities," says Michael Chini, an assistant professor in UCF's Department of Physics and the study's principal investigator. "We are fortunate to have one here at UCF, and there are probably another dozen worldwide. But unfortunately, none of them are truly operated as 'user facilities,' where scientists from other fields can come in and use them for research."

This lack of access creates a barrier for chemists, biologists, materials scientists and others who could benefit from applying attosecond science techniques to their fields, Chini says.

"Our work is a big step in the direction of making attosecond pulses more broadly accessible," Chini says.

"We show that industrial-grade lasers, which can be purchased commercially from dozens of vendors with a price tag of around $100,000, can now be used to generate attosecond pulses."

Chini says the setup is simple and can work with a wide variety of lasers with different parameters.

Attosecond science works somewhat like sonar or 3D laser mapping, but at a much smaller scale. When an attosecond light pulse passes through a material, the interaction with electrons in the material distorts the pulse. Measuring these distortions allows researchers to construct images of the electrons and make movies of their motion.

Typically, scientists have used complex laser systems, requiring large laboratory facilities and clean-room environments, as the driving lasers for attosecond science.

Producing the extremely short light pulses needed for attosecond research - essentially consisting of only a single oscillation cycle of an electromagnetic wave - has further required propagating the laser through tubes filled with noble gases, such as xenon or argon, to further compress the pulses in time.

But Chini's team has developed a way to get such few-cycle pulses out of more commonly available industrial-grade lasers, which previously could produce only much longer pulses.

They compress approximately 100-cycle pulses from the industrial-grade lasers by using molecular gases, such as nitrous oxide, in the tubes instead of noble gases and varying the length of the pulses they send through the gas.

In their paper, they demonstrate compression to only 1.6 cycles, and single-cycle pulses are within reach of the technique, the researchers say.

The choice of gas and duration of the pulses are key, says John Beetar, a doctoral student in UCF's Department of Physics and the study's lead author.

"If the tube is filled with a molecular gas, and in particular a gas of linear molecules, there can be an enhanced effect due to the tendency of the molecules to align with the laser field," Beetar says.

"However, this alignment-caused enhancement is only present if the pulses are long enough to both induce the rotational alignment and experience the effect caused by it," he says. "The choice of gas is important since the rotational alignment time is dependent on the inertia of the molecule, and to maximize the enhancement we want this to coincide with the duration of our laser pulses."

"The reduction in complexity associated with using a commercial, industrial-grade laser could make attosecond science more approachable and could enable interdisciplinary applications by scientists with little to no laser background," Beetar says.

As the United States exceeds 5 million reported coronavirus cases -- the world's first country to do so -- epidemiologists have pinpointed what helped to set the country on this path.

Research from the University of Notre Dame estimates that more than 100,000 people were already infected with COVID-19 by early March -- when only 1,514 cases and 39 deaths had been officially reported and before a national emergency was declared. The study provides insight into how limited testing and gaps in surveillance during the initial phase of the epidemic resulted in so many cases going undetected. The study was published in the Proceedings of the National Academy of Sciences.

"We weren't testing enough," said Alex Perkins, associate professor in the Department of Biological Sciences, an expert in infectious disease epidemiology and population biology and the lead of the study. "The number of unobserved infections appears to be due to very low rates of case detection during a critical time, when the epidemic was really starting to take hold in this country. Part of it was the availability of testing, but another huge part was case definitions and the fact that they were overly restrictive early on."

According to the Centers for Disease Control and Prevention, the first confirmed case of COVID-19 in the United States was reported in January. Early guidance on identifying possible infection included respiratory symptoms, and travel to Wuhan, China -- where an outbreak occurred in December 2019.

"While we were focusing on people coming back from China, we were ignoring people coming from Europe, and actually quite a bit of the initial seeding of the virus into various parts of the United States came from Italy," Perkins said.

While awareness and concern over COVID-19 grew from January to March, it wasn't until Feb. 29 that Washington became the first state to declare a state of emergency -- closing schools and restaurants and imposing restrictions on large gatherings. By mid-March several states followed, but a lack of a coordinated national response created a number of variables as each state decided for itself how to react to a rising number of cases.

By focusing their analysis on the January to March timeframe, when little to no action had been taken on a wide scale, Perkins and his team were able to incorporate a constant into their models. While other studies provide a sense of how school closures and lockdowns slowed the spread of the virus, looking at transmission for the first three months of the year gave the epidemiologists a clearer picture of how the virus emerged and spread throughout the country so quickly.

"It was such a crucial period in terms of how this situation started," said Perkins. "We look at the United States now and compare it to other countries like South Korea or Germany, New Zealand or Vietnam, any number of countries who have done a much, much better job controlling transmission. The key differences really come down to the time period we examine in this study. Those countries had adequate surveillance up and running at that time, whereas we show that throughout most of February the United States missed the vast majority of infections that were already out there. This particular timeframe that we focus on is really important for figuring out how we got here in the first place."

The study used a simulation model beginning on Jan. 1, using data reported by Johns Hopkins University on confirmed cases and deaths, accounting for asymptomatic infections, case fatality rates and local transmission. Perkins and his team first generated an estimate of total infections in the U.S. through March 12. The team then factored in how detection of symptomatic infections changed over time and estimated the number of unobserved infections during this time.

A significant aspect of the analysis is the model's incorporation of many uncertainties that played out in the early days of the epidemic in the U.S., which Perkins said speaks to the inherent nature of a novel and emerging infectious disease. The number of unobserved and unreported infections also speaks to how critical containment strategies are when battling infectious diseases.

"I think the fact that there were so many infections by the second half of February speaks to the importance of and what we could have done in terms of containment," said Perkins. "If you think about Ebola or SARS (severe acute respiratory syndrome) or other emerging infectious diseases, there have been cases that show up in the U.S. or other countries where officials move quickly to get ahead of them. They isolate those people, they do contact tracing -- and transmission is extinguished. I think a lot of us were hoping that would be the situation with this disease. By the time we got to February, the problem had grown so big, containing the virus wasn't possible."

The potential for misdiagnosis and the limitations of surveillance are huge issues across infectious diseases, especially emerging infectious diseases, he added. As illustrated in the COVID-19 study, while public health officials must work quickly to understand how a new virus functions, without appropriate testing or coordinated response strategies the risk grows for infections to go unreported.