Culture

Scientists from the Berlin Institute of Health (BIH), Charité - Universitätsmedizin Berlin and the Thorax Clinic at Heidelberg University Hospital, whose collaboration is taking place under the auspices of the German Center for Lung Research (DZL), have examined samples from non-virus infected patients to determine which cells of the lungs and bronchi are targets for novel coronavirus (SARS-CoV-2) infection. They discovered that the receptor for this coronavirus is abundantly expressed in certain progenitor cells. These cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs. The scientists have now published their findings in The EMBO Journal.

Professor Roland Eils and his colleagues from the Thorax Clinic in Heidelberg initially intended to study why lung cancer sometimes occurs in people who have never smoked. They began by analyzing samples of twelve lung cancer patients. These samples were obtained from the Heidelberg Lung Biobank and came from both the cancerous part of the lungs and the surrounding healthy lung tissue. They also studied cells from the airways of healthy patients, which had been collected in a minimally invasive manner during a bronchoscopy examination performed to rule out lung cancer. The rapidly spreading coronavirus prompted the researchers to take another look at these existing but so far unpublished data. "I was convinced that the data we gathered from these non-coronavirus infected patients would provide important information for understanding the viral infection," says Roland Eils, founding director of the BIH Digital Health Center.

Infection requires receptors and cofactors

"We wanted to find out which specific cells the coronavirus attacks," explains Professor Christian Conrad, who also works at the BIH Digital Health Center. The scientists knew, from studies by BIH Professor Christian Drosten, director of the Institute of Virology at Campus Charité; Mitte, and by others, that the virus's spike protein attaches to an ACE2 receptor on the cell surface. In addition, the virus needs one or more cofactors for it to be able to penetrate cells. But which cells are endowed with such receptors and cofactors? Which cells in which part of the respiratory system are particularly susceptible to SARS-CoV-2 infection? Eils and his colleagues at the BIH and Charité; now used single-cell sequencing technology to examine the cells in the samples from Heidelberg.

60,000 single cells were sequenced

"We then analyzed a total of nearly 60,000 cells to determine whether they activated the gene for the receptor and potential cofactors, thus in principle allowing them to be infected by the coronavirus," reports Soeren Lukassen, one of the lead authors of the study now being published in The EMBO Journal. "We only found the gene transcripts for ACE2 and for the cofactor TMPRSS2 in very few cells, and only in very small numbers." Lukassen and his four co-lead authors Robert Lorenz Chua, Timo Trefzer, Nicolas C. Kahn and Marc A. Schneider discovered that certain progenitor cells in the bronchi are mainly responsible for producing the coronavirus receptors. These progenitor cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs. "Armed with the knowledge of which cells are attacked, we can now develop targeted therapies," explains Professor Michael Kreuter from the Thorax Clinic at Heidelberg University Hospital.

Why does the infection progress so differently?

An interesting additional finding of the study was that the ACE2 receptor density on the cells increased with age and was generally higher in men than in women. "This was only a trend, but it could explain why SARS-CoV-2 has infected more men than women," Eils says. However, he points out, "our sample sizes are still much too small to make conclusive statements, so we need to repeat the study in larger patient cohorts."

"These results show us that the virus acts in a highly selective manner, and that it is dependent on certain human cells in order to spread and replicate," Eils explains. "The better we understand the interaction between the virus and its host, the better we will be able to develop effective counterstrategies." He and the other researchers will next study COVID 19 patients to ascertain whether the virus has actually infected these cells. "We want to understand why the infection takes a benign course in some patients, while causing severe disease in others," Eils says. "So we will also look closely at the immune cells in the infected tissue."

Tech firms provide expertise

Based on a high-performance technology solution designed by Intel, Dell developed a hardware and system architecture that reduced the processing time needed to sequence the 60,000 single cells. Hannes Schwaderer, country manager of Intel Germany, explains: "There are many things we don't know about the coronavirus. This research project and the next steps require enormous computing resources. That's exactly where our expertise can help."

BIH is supporting COVID-19 research

The Berlin Institute of Health (BIH) is helping advance research into the novel coronavirus, SARS-CoV-2, through a targeted program. Professor Axel R. Pries, interim Chairman of the BIH Executive Board and Dean of Charité - Universitätsmedizin, stresses: "In light of the global threat posed by the SARS-CoV-2 virus, we as researchers have a duty to marshal all of our scientific knowledge to understand the virus and its infection strategies as well as the disease progression of COVID-19 patients. Only so can we better identify high-risk patients and develop new therapies and vaccines. Every contribution towards this effort makes a difference."

CLEMSON, South Carolina -- A team of Clemson University College of Science researchers, in collaboration with international colleagues, has reported the first definitive detection of a relativistic jet emerging from two colliding galaxies -- in essence, the first photographic proof that merging galaxies can produce jets of charged particles that travel at nearly the speed of light.

Furthermore, scientists had previously discovered that these jets could be found in elliptical-shaped galaxies, which can be formed in the merging of two spiral galaxies. Now, they have an image showing the formation of a jet from two younger, spiral-shaped galaxies.

"For the first time, we have found two spiral- or disk-shaped galaxies on path for a collision that have produced a nascent, baby jet that has just started its life at the center of one of the galaxies," said Vaidehi Paliya, a former Clemson post-doctoral researcher and lead author of the findings reported in the Astrophysical Journal on April 7, 2020.

The paper is titled "TXS 2116-077: A gamma-ray emitting relativistic jet hosted in a galaxy merger." In addition to Paliya, who is now at the Deutsches Elektronen Synchrotron (DESY) in Germany, the other Clemson authors include associate professor Marco Ajello, professor Dieter Hartmann, and adjunct professor Stefano Marchesi of the department of physics and astronomy.

The fact that the jet is so young enabled the researchers to clearly see its host.

According to Ajello, others have already imaged galactic collisions many times. But he and his colleagues are the first to capture two galaxies merging where there is a fully formed jet pointing at us -- albeit, a very young one, and thus not yet bright enough to blind us.

"Typically, a jet emits light that is so powerful we can't see the galaxy behind it," Marchesi said. "It's like trying to look at an object and someone points a bright flashlight into your eyes. All you can see is the flashlight. This jet is less powerful, so we can actually see the galaxy where it is born."

Jets are the most powerful astrophysical phenomena in the universe. They can emit more energy into the universe in one second than our sun will produce in its entire lifetime. That energy is in the form of radiation, such as intense radio waves, X-rays, and gamma-rays.

"Jets are the best accelerators in the universe -- far better than the super colliders we have on Earth," said Hartmann, referring to accelerators used in high-energy physics studies.

Jets were thought to be born from older, elliptical-shaped galaxies with an active galactic nucleus (AGN), which is a super-massive black hole that resides at its center. As a point of reference, scientists believe all galaxies have centrally located super-massive black holes, but not all of them are AGNs. For example, our Milky Way's massive black hole is dormant.

Scientists theorize that the AGNs grow larger by gravitationally drawing in gas and dust through a process called accretion. But not all of this matter gets accreted into the black hole. Some of the particles become accelerated and are spewed outward in narrow beams in the form of jets.

"It's hard to dislodge gas from the galaxy and have it reach its center," Ajello explained. "You need something to shake the galaxy a little bit to make the gas get there. The merging or colliding of galaxies is the easiest way to move the gas, and if enough gas moves, then the super-massive black hole will become extremely bright and could potentially develop a jet."

Ajello believes that the team's image captured the two galaxies, a Seyfert 1 galaxy known as TXS 2116-077 and another galaxy of similar mass, as they were colliding for the second time because of the amount of gas seen in the image.

"Eventually, all the gas will be expelled into space, and without gas, a galaxy cannot form stars anymore," Ajello said. "Without gas, the black hole will switch off and the galaxy will lay dormant."

Billions of years from now, our own Milky Way will merge with the nearby Andromeda galaxy.

"Scientists have carried out detailed numerical simulations and predicted that this event may ultimately lead to the formation of one giant elliptical galaxy," said Paliya. "Depending on the physical conditions, it may host a relativistic jet, but that's in the distant future."

The team captured the image using one of the largest land-based telescopes in the world, the Subaru 8.2-meter optical infrared telescope located on a mountain summit in Hawaii. They performed subsequent observations with the Gran Telescopio Canarias and William Herschel Telescope on the island of La Palma off the coast of Spain, as well as with NASA's Chandra X-Ray Observatory space telescope.

The brain is permanently exposed to new impressions. Even when sleeping, it does not rest and processes recent experiences. In very early childhood, it has been thought that sleep primarily promotes semantic memory. This includes general knowledge such as the meaning of words. However, scientists at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) Leipzig and the Humboldt University (HU) Berlin, together with researchers from Lübeck and Tübingen, have now shown for the first time in their study published in Nature Communications that babies also build their episodic memory when they nap. This enables them to remember the details of their individual experiences after napping.

The scientists examined this relationship using a three-phase study. During the learning phase, the 14 to 17-month-old children were shown pictures of objects whose names they already knew, containing different cars, balls or dogs. They then heard the appropriate name for each picture. One group of the children spent the following one to two hours sleeping, while a second group stayed awake. In the subsequent test phase, the researchers showed the young participants different pictures again, including those that they had already seen in the learning phase as well as new cars, balls and dogs. Each object was once named correctly and once incorrectly. During all phases of the experiment, the researchers recorded the baby's brain activity using the electroencephalogram (EEG).

The analysis of the EEG activity made it clear: The brain of the children who had slept responded differently in the memory test than that of those who stayed awake - but only in certain cases. If the researchers presented the babies with a ball that they had never seen before and called it a car, the brain responses initially did not differ. In both groups, the so-called N400 component appeared, which occurs when the brain processes inappropriate meanings. The children obviously knew that a ball is not a car.

It was different, however, when the babies viewed a ball from the learning phase and it was called a car. The group that had stayed awake again showed the N400 component, while the group that had slept did not. In the children who had napped, the researchers observed a brain response that was triggered when a ball from the learning phase was again correctly named as such. However, this response did not occur when a new ball was called a ball. The researchers concluded: After sleep, the babies no longer understood the object-word pairs they had previously experienced as naming a meaning. Rather, they recognized them as individual episodes. Object and word were thus merged into a unified event in the memory.

"The results show that sleep not only enables the infant brain to generalize individual experiences, but also to preserve individual experiences in detail and to differentiate them from existing general knowledge," explains first author Manuela Friedrich, researcher at the MPI CBS and HU Berlin. She further hypothesizes: "The fact that a recognized object-word episode is not understood as referring to general knowledge means that its details can be protected from mixing with existing memory."

The results are also interesting with respect to the so-called infantile amnesia, i.e. the phenomenon of not being able to remember one's own early childhood experiences. It has often been assumed that very young children are not yet capable of forming longer-term episodic knowledge. However, the current findings clearly show that even babies can remember events in detail - and sleep contributes significantly to this.

New Rochelle, NY, April 6, 2020--A team of researchers in Wuhan, China have developed a multidisciplinary self-managed home quarantine method that was effective in controlling the source of COVID-19 infection and was useful in alleviating the shortage of medical resources. Click here to read the article free on the Telemedicine and e-Health website.

The case study "Implications for Online Management: Two Cases with COVID-19" describes the use of an online/offline multidisciplinary quarantine observation form, online monitoring, and strict compliance with quarantine measures to treat one mild and one severe case of COVID-19 infection. The mild case was able to be treated entirely at home, while the severe case ultimately required hospitalization.

"In late 2019 and early 2020, the province of Wuhan, China began to see patients with what was eventually known as COVID-19. While the pandemic has now spread across the globe, this group in China has implemented some effective ways of managing patients via telemedicine tools. These tools proved quite useful and can be seen as one effective example to follow," says Charles R. Doarn, MBA, Editor-in-Chief of Telemedicine and e-Health.

The multidisciplinary quarantine team was comprised of experts in medicine, rehabilitation, psychology, and nursing. Patients described their symptoms and conditions online using a quarantine observation form at least two times per day. The quarantine team created a WeChat group to ease communication. Nursing experts provided guidance on quarantine and disinfection and oversaw patients' diets and sleep schedule. Rehabilitation experts developed a feasible rehabilitation plan, and psychotherapists encouraged patients to stay optimistic. Importantly, the quarantined patients were not alone, as they had regular contact with the quarantine team, aimed at increasing their confidence in recovery and enhancing self-management capabilities.

A new report calls for measures to protect elderly people in long-term care facilities and their caregivers who are particularly vulnerable to the COVID-19 pandemic.

Elderly people in long-term care facilities are at high risk of dying from COVID-19 and the risk of transmission of the virus is also especially high at these residences.

Writing in the Journal of Aging & Social Policy, the authors emphasize that being vigilant about the health of the elderly in long-term care is essential not only for their health, but also to protect the healthcare system from becoming overwhelmed by severe COVID-19 cases.

Lead author William Gardner, Professor of Epidemiology at the University of Ottawa, Canada said: "If COVID-19 sweeps through a single long-term care facility, this surge in caseload could overwhelm local hospital capacity. Local hospitals may already be under severe strain due to an influx of coronavirus patients during the current pandemic."

In response to the pandemic many long-term care facilities have adopted strict new access and visitation restrictions to protect residents from infection. But locking down long-term healthcare facilities, possibly for several months, raises other concerns.

"A lack of visits from family and friends will increase the isolation of elderly residents of long-term care facilities. Unfortunately, isolation will also increase their vulnerability to abuse and neglect," said Gardner. "If we do not watch closely, many elderly people might be effectively abandoned as the outbreak continues."

The authors emphasize the urgent need for new measures to protect elderly residents of long-term facilities during the COVID-19 pandemic. They recommend that:

Long-term care facilities should be priority sites for COVID-19 testing and personal protective equipment.

Policies should be developed to ensure that long-term care facilities remain adequately staffed and that infection control protocols are closely followed.

To protect residents and staff, supervision of long-term care facilities should remain a priority during the pandemic.

The authors also emphasize that the fewer people who get infected in the general population, the lower the risk of infection for long-term care residents. Similarly, the fewer in the general population who get hospitalized, the more capacity will be available for long-term care residents.

"The most important thing that we can all do to help protect these vulnerable groups is to minimise disease transmission by following guidance from public health officials on handwashing and social distancing," said Gardner.

ABERDEEN PROVING GROUND, Md. (April 7, 2020) - Team disagreements might be the key to helping Soldiers identify objects in battle, researchers say.

While studies on combat identification typically focus on how technology can help identify enemy forces, researchers sought to understand how teams work together to identify armored vehicles--using only their training and each other.

"We wanted to know what factors would contribute the most to their success," said Dr. Anthony Baker, a scientist at the U.S. Army Combat Capabilities Development Command's Army Research Laboratory, who executed the study while a doctoral student at Embry-Riddle Aeronautical University. "While previous lab studies of combat identification have looked at the performance of an individual, this is the first lab study to our knowledge that considers team combat identification, especially without any technological aids like an automated combat identification system. This was key for helping us understand the aspects of the team, and its members, that contribute the most to their ability to understand and identify what they are seeing."

The Human Factors journal published the research, "Team Combat Identification: Effects of Gender, Spatial Visualization, and Disagreement," in its February issue.

Spatial visualization skills are particularly important for noticing the finer details that distinguish combat vehicles, which are more difficult to identify from the front than other angles, Baker said.

"Combat vehicles can be broadly similar in their shape and components," Baker said. "For example, many tanks have a similar general shape involving a large, blocky body with a rotating turret. Because of this, few viewing angles may highlight easily-identifiable cues, making it difficult to tell exactly what it is you're looking at."

In this study, researchers prepared pictures and videos of 10 armored vehicles from different angles and views, and presented them to 39 two-person teams. The researchers identified every point when the participants disagreed about which vehicle they saw.

Researchers found that teams that disagreed more performed better at combat identification, regardless of whether their disagreements actually resulted in more correct answers. The data suggested that disagreeing with a team member's first guess caused the team to verify why they identified a vehicle a certain way.

"In other words, when the team disagreed, they had to justify an answer by recounting the details of what they had seen," Baker said. "This process of recalling and discussing details caused teams to think more deeply about their original responses, compared to teams with fewer disagreements that may have simply trusted what the other teammate believed."

Previous studies show that spatial skills are very important when an individual performs combat identification, with men having a slight advantage over women in spatial visualization scores, Baker said; however, the data from this study suggest that while men typically have a slim advantage over women in spatial ability measures, team gender composition was not an important indicator of overall performance.

"The team members' individual spatial abilities--and the team's ability to communicate--are more important than gender," Baker said. "You can have a team of men with lower spatial skills that would likely perform worse at this task than a team of women with better spatial skills, or any other combination."

This research reinforces that to understand how a team does its job, one must consider both individual differences such as spatial skills, and team processes such as communication, Baker said.

WASHINGTON, April 7, 2020 -- Tiny biohybrid robots on the micrometer scale can swim through the body and deliver drugs to tumors or provide other cargo-carrying functions. The natural environmental sensing tendencies of bacteria mean they can navigate toward certain chemicals or be remotely controlled using magnetic or sound signals.

To be successful, these tiny biological robots must consist of materials that can pass clearance through the body's immune response. They also have to be able to swim quickly through viscous environments and penetrate tissue cells to deliver cargo.

In a paper published this week in APL Bioengineering, from AIP Publishing, researchers fabricated biohybrid bacterial microswimmers by combining a genetically engineered E. coli MG1655 substrain and nanoerythrosomes, small structures made from red blood cells.

Nanoerythrosomes are nanovesicles derived from red blood cells by emptying the cells, keeping the membranes and filtering them down to nanoscale size. These tiny red blood cell carriers attach to the bacterial membrane using the powerful noncovalent biological bond between biotin and streptavidin. This process preserves two important red blood cell membrane proteins: TER119 needed to attach the nanoerythrosomes, and CD47 to prevent macrophage uptake.

The E. coli MG 1655 serves as a bioactuator performing the mechanical work of propelling through the body as a molecular engine using flagellar rotation. The swimming capabilities of the bacteria were assessed using a custom-built 2D object-tracking algorithm and 20 videos taken as raw data to document their performance.

Biohybrid microswimmers with bacteria carrying red blood cell nanoerythrosomes performed at speeds 40% faster than other E. coli-powered microparticles-based biohybrid microswimmers, and the work demonstrated a reduced immune response due to the nanoscale size of the nanoerythrosomes and adjustments to the density of coverage of nanoerythrosomes on the bacterial membrane.

These biohybrid swimmers could deliver drugs faster, due to their swimming speed, and encounter less immune response, due to their composition. The researchers plan to continue their work to further tune the immune clearance of the microrobots and investigate how they might penetrate cells and release their cargo in the tumor microenvironment.

"This work is an important stepping stone in our overarching goal of developing and deploying biohybrid microrobots for therapeutic cargo delivery," author Metin Sitti said. "If you decrease the size of red blood cells to nanoscale and functionalize the body of the bacteria, you could obtain additional superior properties that will be crucial in the translation of the medical microrobotics to clinics."

Bacterial canker of tomato is a disease that leads to wilt, cankers, and eventually death. The disease was first discovered in Grand Rapids, Michigan, in 1909, but annual outbreaks now affect tomato production areas worldwide. For some farmers, bacterial canker can be devastating and spoil an entire season's planting.

Bacterial canker is caused by the pathogen Clavibacter michiganensis, which infects commercially bred tomatoes by colonizing the xylem, a series of tubes that transports water and minerals throughout the plant. There are no commercially available tomatoes resistant to bacterial canker and management options are limited. However, breeders have known that wild tomato species are less susceptible to bacterial canker, but this knowledge is limited.

Scientists at the School of Integrative Plant Science at Cornell University were interested in understanding how C. michiganensis colonized the xylem in wild tomato and comparing to colonization of cultivated tomatoes. They found a significant difference, according to the paper published in Phytopathology.

F. Christopher Peritore-Galve, lead author of this paper, explains: "Interestingly, the pathogen colonizes to high densities close to the inoculation site in wild tomatoes, but it is found in much lower densities 5 and 10 centimeters above that site, meaning that the bacteria are unable to spread through the xylem as well as in cultivated tomato xylem."

Additional research showed that the pathogen was restricted to the protoxylem vessels in vascular bundles of wild tomato.

"Protoxylem are early formed xylem vessels that are smaller in diameter that enable water transport during early, rapid plant growth," said Peritore-Galve. "We currently do not know why C. michiganensis preferentially colonizes these vessels, but that will be an avenue of future research."

Understanding what makes wild tomatoes able to tolerate this pathogen may help with future breeding efforts. For more information about this study, read "Characterizing Colonization Patterns of Clavibacter michiganensis During Infection of Tolerant Wild Solanum Species."

OAK BROOK, Ill. (April 7, 2020) - A multinational consensus statement from the Fleischner Society on the role of chest imaging in the management of patients with COVID-19 was jointly published today in the journals Radiology and Chest.

"We need to understand that conditions across the globe vary greatly. Our goal in developing this statement was to offer guidance that is sensitive to these differences and applicable broadly," said Geoffrey D. Rubin, M.D., George B. Geller Professor of Cardiovascular Research, professor of radiology and bioengineering at Duke University School of Medicine in Durham, North Carolina.

The statement represents the collective opinions and perspectives of thoracic radiology, pulmonology, intensive care, emergency medicine, laboratory medicine and infection control experts practicing in 10 countries, representative of the highest burden of COVID-19 worldwide.

"The willingness of experts from around the world to pause from their care of patients to contribute their knowledge and experience toward this international consensus was inspiring," Dr. Rubin said.

Chest CT and X-ray are key tools in the diagnosis and management of numerous respiratory ailments, but their role in the management of COVID-19 has not been considered within the context of many variables, including the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints.

"The Fleischner statement was uniquely comprised of a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments," said Radiology Editor David A. Bluemke, M.D.

The panel evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions and resource constraints.

Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest X-ray and CT in the management of COVID-19.

The results suggested that imaging is not routinely indicated in asymptomatic individuals or patients with suspected COVID-19 and mild clinical symptoms. Use of chest imaging is indicated in patients with COVID-19 who have worsening respiratory status. Imaging is also indicated for patients with moderate to severe features of COVID-19 regardless of COVID-19 test results.

In a resource-constrained environment (lack of personal protection equipment or availability of COVID-19 testing), imaging is indicated for medical triage of patients with suspected COVID-19 who present with moderate to severe clinical features and a high pre-test probability of disease.

The panel also found that CT is appropriate in patients with functional impairment and/or hypoxemia (low level of oxygen in the blood) after recovery from COVID-19. When there is known community transmission, evidence of COVID-19 has been incidentally found on CT scans. In these cases, patients should have COVID-19 testing using a reverse-transcription polymerase chain reaction (RT-PCR) viral assay.

The authors note that this consensus statement represents opinion at a moment in time within a highly dynamic environment where the status of regional epidemics and the availability of critical resources to combat those epidemics vary daily. Recommendations may undergo refinement as the situation evolves.

"Currently, no therapy has been confirmed to alter the course of COVID-19, there is no known cure, and there is no vaccine for prevention," Dr. Rubin said. "As effective treatments are developed, thoracic imaging may find new roles by establishing treatment response or characterizing patients as likely responders to novel therapies."

RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources. RSNA's COVID-19 Resources page houses the latest guidance, original research, image collection and more. The page will be updated on an ongoing basis.

An associated special edition podcast from Dr. Bluemke is available.

WASHINGTON, April 7, 2020 -- Infertility is estimated to affect 9% of reproductive-aged couples globally, and many couples consequently turn to assisted reproductive technology (ART). Selecting embryos with maximum development potential plays a pivotal role in obtaining the highest rate of success in ART treatment, which ultimately determines whether a couple gets pregnant.

The conventional way to select embryos is based mainly on a morphological score, a score based on the form of the embryo. This method, however, is subjective, and there is inherent variability in how embryologists score embryos' morphology.

In comparison, researchers have found it more objective to evaluate the quality of an embryo by detecting the content of proteins secreted by the embryo. In a paper for Biomicrofluidics, from AIP Publishing, a method to detect trace proteins secreted by embryos using microfluidic droplets and multicolor fluorescence holds promise to select embryos for ART. The researchers analyzed spent embryo culture media from 30 patients in Shenzhen, China, collected between May to July 2019.

Extensive research in ART in secretomics, the analysis of the secretome, or the secreted proteins of a cell, tissue or organism, allows for the detection of these trace proteins. However, researchers are faced with a challenge because of the very small quantities of these proteins and the limits of detection tools.

"The proposed method aims to predict the developmental potential of the embryo based on the secretomics. We only need a small drop of medium to achieve this," said Yong Zeng, chief scientist of the Fertility Center at Shenzhen Zhongshan Urology Hospital in Shenzhen, China.

The team used microfluidic chips, which are tiny devices that enable a small amount of liquid to be processed or visualized. Zeng and his team were able to ensure the accuracy of their results by using a multi fluorescence detector (MFD).

Fluorescent magnetic beads and beta-glucanase enzyme-induced fluorescence products have different excitation and emission wavelengths and can be detected by MFD. The team was consequently able to eliminate the false positive signals generated by free beta-glucanase.

Using this ultrasensitive detection method, the researchers found that human corionic gonadotropin secreted by top-quality blastocysts was significantly higher than that of non-top-quality blastocysts and the embryos which did not develop into blastocysts. Human corionic gonadotropin is a protein secreted by the placenta and also secreted by embryo cultured in vitro.

"In the future, we will test other different kinds of proteins secreted by the embryo and analyze the relationship between those proteins and embryo quality," said Zeng.

Since various embryo-secreted proteins often appear in very small amounts, they will also work to develop increasingly sensitive and multifactor protein detection systems.

WOODS HOLE, Mass. - A selective mating experiment by a curious butterfly breeder has led scientists to a deeper understanding of how butterfly wing color is created and evolves. The study, led by scientists at University of California, Berkeley, and the Marine Biological Laboratory, Woods Hole, is published today in eLife.

When the biologists happened upon the breeder's buckeye butterflies--which normally are brown--sporting brilliant blue wings through selective mating, they jumped on the chance to explore what caused the change in color of the tiny, overlapping scales that produce the wing's color mosaic and pattern. They found that buckeyes and other Junonia species can create a rainbow of structural colors simply by tuning the thickness of the wing scale's bottom layer (the lamina), which creates iridescent colors in the same way a soap bubble does.

Structural color, often used in butterflies and other animals to create blue and green, is created by microscopic structures interacting with light to intensify some colors and diminish others. In contrast, pigmentary coloration is created by the absorption of specific colors (wavelengths) of light and is commonly employed to create colors such as yellow, orange, and brown.

"It was a surprise to find that the lamina, a thin sheet that looks very simple and plain, is the most important source of structural color in so many butterfly wing scales," says first author Rachel Thayer. Previous studies of structural coloration had largely focused on some extreme examples and mostly involved analyzing complex, 3D shapes on the top of the scales.

First, the team showed that blueness in the selectively bred buckeye wings was, in fact, structural color and was generated largely by the lamina. They then compared these blue scales with wild-type brown scales, and found the same general architecture except the lamina was about 75 percent thicker in the blue scales. Finally, they measured lamina thickness in nine species of Junonia and a tenth species, Precis octavia, and found a consistent relationship with scale color.

"In each Junonia species, structural color came from the lamina. And they are producing a big range of lamina thicknesses that create a rainbow of different colors, everything from gold to magenta to blue to green," says Thayer. "This helps us understand how structural color has evolved over millions of years." The color shifts as lamina thickness increases according to Newton's series, a characteristic color sequence for thin films, the team found.

"The color comes down to a relatively simple change in the scale: the thickness of the lamina," says senior author Nipam Patel, director of the Marine Biological Laboratory. "We believe that this will be a genetically tractable system that can allow us to identify the genes and developmental mechanisms that can control structural coloration." They identified one gene, optix, that can regulate lamina structural colors, and are currently searching for other candidates.

It was fortunate that the butterfly farmer, Edith Smith, had chosen buckeyes (Junonia coenia) for her mating experiment. For a variety of reasons, it is an ideal species for scientists to work with. "The buckeye genome is sequenced and other labs are working with it and have developed a number of experimental tools and protocols," Patel says. "And it grows reasonably well in the lab, which is a big plus because many butterflies can be hard to raise."

Smith's bred buckeyes, which displayed "rapid evolution" from brown scales to blue, helped them to understand that the same, simple mechanism of tuning lamina thickness can facilitate evolutionary change that can span just several generations or millions of years.

April 07, 2020-- Researchers have identified the most common clinical characteristics of 109 patients with COVID-19 related pneumonia who died in Wuhan, China in the early stages of the coronavirus pandemic, according to a new study published online in the Annals of the American Thoracic Society.

In "Hospitalization and Critical Care of 109 Decedents With COVID-19 Pneumonia in Wuhan, China," Huan-Zong Shi, MD, PhD, and co-authors report on the age, comorbidities (other diseases), treatments and other commonalities among patients who died from this viral infection in three Wuhan hospitals between Dec. 25, 2019 and Feb. 24, 2020. The study was conducted to describe the hospitalization and critical care of patients who died from COVID-19 pneumonia.

"Mortality due to COVID-19 pneumonia was concentrated in patients above 65 years of age, especially those with major comorbidities," stated Dr. Shi, professor and director of the Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University. "We also found that patients who were admitted to the ICU lived longer than those who didn't. Our findings should aid in the recognition and clinical management of such infections, especially in ICU resource allocation."

The researchers looked back at the medical records of 109 deceased patients (out of 1,017) with confirmed COVID-19 pneumonia admitted to three Wuhan hospitals: Wuhan Pulmonary Hospital, which is designated as a "COVID-19 hospital," Tianyou Hospital affiliated with Wuhan University of Science and Technology, and Central Hospital of Wuhan. They recorded information on patients' demographics, clinical symptoms, laboratory results on admission and during hospitalization, treatment and date of death. The team created a database containing this information, and then cross-checked it. They then performed statistical analyses.

The average age of these patients was 70.7 years. Eighty-five suffered from comorbidities. The most common conditions were hypertension (high blood pressure), cardiovascular or cerebrovascular diseases and diabetes. All 109 patients were critically ill at hospital admission, and their most common condition was progressive shortness of breath (dyspnea). Prof. Shi observed, "Dyspnea was the most remarkable symptom that rapidly worsened."

Although all of these patients needed ICU care, only 46.8 percent were admitted to the ICU because of a bed shortage. Although all of the patients studied died, patients who were in the ICU group in comparison to the non-ICU group, lived an average of 15.9 days vs. 12.5 days following hospitalization.

"It is not surprising that there were approximately twice as many men as women among non-survivors with COVID-19 pneumonia," stated Prof. Shi. "In most infectious diseases and related conditions such as sepsis and septic shock men always represent a larger proportion of cases and have higher mortality rates."

All patients received antibiotics to treat secondary infections and nearly all received antivirals, while all ICU patients also received antifungal drugs. Other medicines, including glucocorticoids and intravenous immune globulin, were given to some patients. Oxygen therapy of various types was given to all patients.

Based on their observations and analyses, the authors concluded: "Since multiple organ failure, especially respiratory failure and heart failure, occurred rapidly after hospital admission, an organ protection strategy and ICU care should be provided as soon as possible to patients with severe COVID-19 pneumonia in order to prolong their survival. A social distancing policy should also be proposed to slow the rate of cases and prevent health care systems from being overwhelmed by patients for whom they cannot provide ICU care."

ITHACA, N.Y. - Researchers from Cornell University have identified a possible target for antiviral treatment for COVID-19.

The researchers initially set out to analyze the structure and characteristics of SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus), with a focus on the spike protein - specifically the fusion peptide - that allows these viruses to infect cells by transferring their genome.

As the current pandemic escalated, the researchers compared the biological sequences of the fusion peptides of SARS-CoV to SARS-CoV-2, the virus that causes COVID-19, and found them to be a 93% match.

Susan Daniel's lab specializes in the biophysics of the cell membrane envelope; Gary Whittaker's team studies the entry of influenza and coronaviruses into host cells. Their combined group is drilling down into the intricate procedure of membrane fusion - a critical part of the mechanism by which coronaviruses spread.

Membrane fusion is a multistep process that begins with the virus recognizing that it's found the right type of cell to infect. To do this, the virus receives feedback from the chemical environment, including cues like the receptor that the host cell presents. The virus then attaches to the host cell receptor by way of the spike protein.

Next, a piece of the spike protein, called the fusion peptide, interacts directly with the host cell membrane and facilitates merging to form a fusion pore, or opening. The virus then transfers its genome into the host cell through this pore. These genomic instructions essentially commandeer the host's machinery to produce more viruses.

The group found that calcium ions interacting with the fusion peptide can change the peptide's structure, and how it interacts with membranes in ways that promote infection in MERS and SARS. Now, the researchers are turning their attention to SARS-CoV-2 because the fusion peptides are consistent in all three viruses.

The team is hopeful the research can illuminate some of the chemistry-related questions surrounding COVID-19, such as how it was able to move into humans, what chemical cues facilitated that process, and why the virus is able to replicate so easily in the respiratory tract. The team's findings have led to supplemental funding from the National Institutes of Health (NIH), through its Research Project Grant program, to develop an antibody that could block the virus's entry by interacting with the fusion peptide.

Few technologies have made as big a splash in recent years as CRISPR/Cas9, and rightfully so. CRISPR/Cas9, or clustered regularly interspaced palindromic repeats (CRISPR) and associated genes, is a bacterial gene editing toolbox that allows researchers to edit genomic sequences much more precisely and efficiently than previously possible, opening up doors to new ways of doing research. As with many new biotechnologies, the application of CRISPR in biology began with genetic model organisms such as Arabidopsis thaliana. In research presented in a recent issue of Applications in Plant Sciences, Shengchen Shan and colleagues review the prospects for expanding the use of CRISPR for research beyond genetic model plant species.

"Developing CRISPR/Cas9 in nongenetic models holds enormous potential in plant biology," says Shan, a PhD candidate at the University of Florida, Gainesville. "Almost all CRISPR applications have focused on genetic models, like Arabidopsis and major crops. However, many nongenetic models are economically important and/or biologically significant."

Indeed, while our in-depth knowledge of the biology of genetic model species makes them enormously valuable for research, these species represent only a tiny sample of plant diversity. Much could be gained from expanding genetic studies of non-model species, including through the use of new tools like CRISPR.

Polyploidy, or whole genome duplication, is one example Shan and colleagues highlight of a research area that CRISPR could revolutionize. "We are very excited about future CRISPR/Cas9 applications in studies of evolutionary biology, especially the role of polyploidy in plant evolution. Polyploidy is a major evolutionary force in land plants, but the genotype-phenotype relationships following genome doubling are largely unknown," explains Shan. "CRISPR/Cas9 could be used to disrupt the observed genetic patterns in polyploids, and therefore, by comparing phenotypes of the mutant and wild-type plants, researchers will be able to reveal the biological underpinnings of many intriguing genetic consequences, such as nonrandom gene losses following polyploidy."

Researchers looking to study non-genetic model species using CRISPR will face some technical obstacles, including difficulties in genetic transformation, the process of introducing and expressing foreign genes in a plant species. However, looking to transformation systems established in closely related species can help. According to Shan, "The biggest barrier is developing the transformation system. Although we have summarized a few commonly used transformation strategies, plant transformation is a very species-specific process." He goes on to note, "As we reviewed, both transformation and CRISPR systems from a phylogenetically closely related genetic model species can be adapted for an initial attempt of establishing CRISPR in a newly studied plant species." In this way, the development of transformation and CRISPR systems in genetic models has helped pave the way for expanding CRISPR beyond these species.

The research done using CRISPR in genetic model species thus far has lowered the bar for entry in other ways too, as researchers have optimized techniques, hammered out details, and built up expertise in the use of this exciting new technology. "For people studying ecology or evolutionary biology, using a state-of-the-art technique in molecular biology research, like CRISPR/Cas9, might seem intimidating," says Shan. "However, based on our own experience, with the help from collaborators from a molecular biology lab, it is not that hard!"

In a pilot study in adults with autism and depression, transcranial magnetic stimulation, or TMS, was effective in reducing depressive symptoms and had some effects on autistic symptoms, report researchers at the Medical University of South Carolina in Autism Research. This study suggests that TMS warrants further study as a potential treatment for adults with both depression and autism.

TMS has been used as a therapy for treatment-resistant depression and is a candidate treatment for depressed adults with autism. It uses a magnet placed on the scalp to generate electromagnetic pulses that activate neurons in the brain near the magnet.

The study was performed by a team of MUSC researchers led by M. Frampton Gwynette, M.D., director of the General Psychiatry Clinic, Project Rex and the Autism News Network, and Mark George, M.D., a pioneer in TMS, is the Layton McCurdy Endowed Chair in Psychiatry and director of the Brain Stimulation Lab.

People with autism have challenges with social interactions and communication. For example, they might not make eye contact, or they might hold one-way conversations. They can also have restricted interests, fixating on a singular interest, such as trains, for instance, and everything about them, as well as exhibiting repetitive behaviors, such as rocking or hand flapping when excited.

Such communication challenges can make autism very isolating, according to Gwynette, and render people with autism more prone to depression.

"You'll see very high rates of major depressive disorder in adults with autism, up to 26-50%," explained Gwynette. "When they have depression, it tends to be more severe than in typically developing individuals. They're also more likely to have suicidal ideation and more likely to attempt suicide. In addition, their depression is more likely to be refractory to treatment."

In Gwynette's experience, depressive symptoms can in turn make autism symptoms more challenging.

"We're really swimming upstream trying to treat this group," said Gwynette. "We also know that our standard antidepressant medications are not as effective or as well-tolerated in adults with autism because they're prone to irritability. Sometimes, the antidepressants can make their autism symptoms worse, so it's a really difficult thing to treat."

No treatments for core autism symptoms have been approved by the Food and Drug Administration, so new therapies to treat patients with both autism and depression are urgently needed.

In the study, the researchers recruited 13 adults ages 18-65 with depression and autism to participate in 25 daily TMS treatments. The treatments targeted the left dorsolateral prefrontal cortex, a brain region associated with depression.

After treatment, 70% of participants had a decrease in depressive symptoms, and 40% experienced remission. No changes were seen in self-reported autism symptoms. However, people who knew the participants detected decreases in repetitive behaviors, hyperactivity and irritability.

Overall, the repetitive TMS treatments were well-tolerated, with two participants withdrawing due to anxiety or irritability. Side effects included fatigue, headache and scalp discomfort.

Limitations of the study included its small number of participants and the fact that all participants received the treatment and knew about the treatment. Further conclusions will need to be derived from larger studies that randomize patients to either TMS or a sham intervention and "blind" them as to which treatment group they are assigned.

This study provides early evidence that TMS is safe for treating adults with autism and depression and shows promise in treating depression. These findings will need to be confirmed in future studies. More studies are also needed to elucidate the role of TMS in treating autism symptoms.

George and Gwynette are both optimistic about the future role of TMS in patients with autism and depression and eager to see the results of the next round of studies.

"Daily left prefrontal TMS, as we used in this study, appears to treat not just pure depression but also depression arising in the setting of autism and other disorders like Alzheimer's," said George. "These are promising results. I'm particularly intrigued by the improvements not just in depressive symptoms but also in other symptoms in the autism spectrum. That was unexpected. The true answer will come with a double-blind trial."

"I'm optimistic, as an autism specialist, that TMS will have a role in treating mental and comorbid conditions that come along with autism but also autism itself," said Gwynette.