Culture

Swansea University researchers have discovered two new species of parasite, previously unknown to science, in crabs in Swansea Bay, during a study on disease in the Celtic and Irish Seas.

Both species are emerging pathogens, and were discovered infecting the common shore crab, so they could potentially have damaging effects on fisheries and other marine species. The researchers' discovery will help inform measures to reduce this risk.

The common European shore crab is native to the UK, Ireland and the north east Atlantic. It shares this habitat with many commercially important species such as the edible crab and several lobster species.

The shore crab is also an invasive species in other countries as it can survive in a wide range of different environments, potentially carrying diseases with it.

The discovery was made by researchers from the BlueFish project in the University's Biosciences department. They were carrying out a year-long, multi-disease monitoring survey over two locations in Swansea Bay: Mumbles Pier and Prince of Wales dock.

When they were examining the crabs, they noticed parasites in the blood which they had never seen before.

They used a range of methods, from analysing diseased tissue from the crabs, to examining the parasite DNA using a technique called Sanger sequencing. The sequences seemed to indicate a new species.

Collaborators at the Natural History Museum, London and CEFAS in Weymouth were able to generate a longer sequence of the parasite DNA, verifying the presence of two new parasite species.

The team have named the new species Haplosporidium carcini, after the host species, (Carcinus maenas) and Haplosporidium cranc, with 'Cranc' being Welsh for crab, a reference to both their Ireland-Wales funding, and the location of discovery, or 'Welsh' nature of the parasite.

The researchers also observed that:

Infections were found in only one of the two locations - Mumbles Pier, Swansea Bay

Infection levels were very low, around 1-2%

Dr Charlotte Eve Davies from Swansea University College of Science, Scientific Officer on the Bluefish project, said:

"It is so important to understand the role of the shore crab in hosting parasites and disease, and if they are passing these on to other commercially important crustaceans.

The systematic approach we used, employing different detection methods, is vital in getting the best possible picture of these new pathogens.

Our study and broader work also suggest that the overall habitat - physical surroundings and ecosystem -may be influencing the presence and prevalence of pathogens, depending on the location.

It's been really exciting to be able to characterise two new species and a real team effort. Professor Andrew Rowley first noticed these new parasites and named them parasites x, y and z for months before we realised that we really did have a new species!"

The research was published in the journal Parasitology.

[Wednesday, July 14th Fruita, Colorado] Top predators dinosaurs like the Allosaurus and Ceratosaurus devouring dinosaur remains isn't all that surprising, but the smaller creatures feasting on dinosaur remains may just give us a more complete picture of what life was like at Mygatt-Moore Quarry outside Fruita, Colorado 152 million years ago. A new study out in PeerJ on Wednesday, July 15th, 2020 authored by Museums of Western Colorado's Paleontologist Dr. Julia McHugh, looks at the insect species who feasted on decaying dinosaurs back in the Jurassic period.

Researchers Dr. Julia McHugh (Museums of Western Colorado, Colorado Mesa University), Dr. Stephanie K. Drumheller (University of Tennessee), Anja Riedel (Colorado Mesa University), and Miriam Kane (Colorado Mesa University) examined more than 2,300 fossil bones over a two-year study and found over 400 traces left by insects and snails, a surprisingly high number. The marks researchers found on the fossils also came from at least six different invertebrates. These findings are a huge step to understanding the long-lost paleo diversity, and paleo climate of the Jurassic period.

It also gave researchers a better understanding of just how stinky the Jurassic period was too. The abundance of traces meant that the dinosaur carcasses must have been unburied for a long time - 5 months to 6 years or more according to this new study. "Large carcasses take a long time to decompose. The smell from a dead mouse in your basement is bad enough, but then imagine that mouse was a 65-foot long animal! The stench of rotting meat would have been a magnet for carrion insects and other scavengers," Dr. McHugh explains.

In a clinical trial evaluating a novel immunotherapy option for cancer treatment, a child with rhabdomyosarcoma, a form of muscle cancer, that had spread to the bone marrow, showed no detectable cancer following treatment with chimeric antigen receptor (CAR) T cells that were engineered to target the HER2 protein on the surface of the cancer cells.

The trial, conducted by researchers at Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, was recently published in the journal Nature Communications.

"This child's cancer was considered high risk because it had not responded to standard chemotherapy. As a result, this child was a candidate to receive a promising new CAR T cell therapy, a personalized form of immunotherapy that redirects the patient's own immune T cells to recognize and fight the tumor," said first and corresponding author Dr. Meenakshi Hegde, assistant professor of pediatric hematology-oncology at Baylor College of Medicine and Texas Children's.

About 75 percent of the tumor cells in this patient displayed a protein on their surface called HER2. The researchers reprogrammed the T cells to target the HER2 protein by genetically engineering them to express CAR molecules that recognize the HER2-expressing (HER2+) cancer cells.

In a previous clinical trial, the HEROS study, the researchers found that CAR T cells directed at HER2+ tumor cells had a favorable safety profile. This early generation CAR T cell treatment resulted in clinical benefit in a small subset of patients, but it did not eradicate their tumors.

"From the HEROS trial, we learned that HER2-CAR T cells expanded but did not persist in the patients, which could in part explain the lack of anti-tumor responses," said Hegde, who also is part of Baylor's Dan L Duncan Comprehensive Cancer Center.

To overcome this limitation, Hegde and her colleagues added successive HER2-CAR T cell infusions along with low-dose chemotherapy to delete normal T cells as a strategy to improve the expansion and persistence of the infused HER2-CAR T cells in a trial they called, HEROS 2.0. The lymphodepleting chemotherapy administered before transferring HER2-CAR T cells eliminated the patient's existing immune cells, creating a space for the engineered CAR T cells to expand in the patient.

"Although the child had a lasting response to HER2-CAR T cells with no tumor detected, the cancer returned six months after we stopped the T cell infusions. Fortunately, the child achieved a second remission after retreatment with HER2-CAR T cells," Hegde said. "Considering the several challenges in successfully treating solid tumors using CAR T cells, achieving this exceptional tumor response is very encouraging."

At the time of this report, the child is 19 months off T cell treatment and remains healthy and cancer free.

New insights into how this exceptional recovery occurred

The sustained tumor response in this child has provided the researchers important insights into how the cancer was eliminated. The CAR T cells were developed to recognize and attack HER2+ cancer cells. Although not all cancer cells expressed HER2 on the cell surface, the tumor was eliminated in its entirety prompting the question of how the HER2-negative cancer cells were eradicated.

"We found evidence suggesting that, following the infusion of HER2-specific CAR T cells, the patient's own immune system was recruited to act against the tumor, which might help explain the durable complete response," Hegde said. "We plan on conducting more detailed experiments in a larger group of patients treated with HER2 CAR T cells to better understand the involvement of the patient's immune system in eliminating the cancer."

"It is fascinating to see remodeling of the patient's T cell compartment and development of antibodies directed against proteins implicated in tumor survival and metastasis during the course of treatment in this child. The immune activation mechanisms and associated tumor targets unfolded during the acquired response, could inform novel approaches to fight difficult-to-treat cancers," said Dr. Sujith Joseph, senior scientist at Baylor's Center for Cell and Gene Therapy, who conducted the in depth evaluation of the patient's immune response.

"This study shows that CAR T cells could perhaps act as vaccines by exposing cancer proteins to the patient's immune system. With more understanding and further refinement of their design, CAR T cells could be effective against some incurable malignancies," said senior author Dr. Nabil Ahmed, associate professor of pediatrics and immunology at Baylor and Texas Children's Hospital.

By now, we’re all aware that COVID-19 is especially dangerous for older adults—the older you are, the higher your risk for serious illness and even death if you contract the virus. Because there is no treatment or a vaccine yet, it’s vitally important that we practice social distancing and wear masks to protect ourselves from disease.

But as we work to keep ourselves safe, we also need to be sure we’re not falling into physical inactivity. When we cut ourselves off from shopping, walking in malls, and going to the gym and other places where we can exercise, we can become sedentary. Older adults who don’t get regular exercise may become prone to chronic diseases, weakened muscles, and frailty.

Researchers from the University of Sao Paulo in Brazil recently reported on the dangers of physical inactivity for older adults during COVID-19. Their paper was published in the Journal of the American Geriatrics Society.

The researchers noted that it only takes five to 10 days of physical inactivity for your muscles to begin shrinking and wasting away. This can speed the progression of sarcopenia (muscle loss) and can lead to chronic diseases.

Studies also show that older adults who walk fewer than 1,500 steps a day can lose 4 percent of the muscle tissue in their legs in just two weeks.

Although it’s too soon to know how the COVID-19 pandemic will impact physical activity, researchers say that wearable trackers (such as Fitbit) provide early estimates. Information from 30 million users worldwide estimate a 12 percent step-count decline in the United States (comparing the week of March 22, between 2019 and 2020), and an even greater decline in other countries.

Having an adequate amount of muscle mass enables you to be strong; being weak or frail is a known risk factor for death in older adults. Two weeks of inactivity (a 75 percent daily step reduction) has been shown to decrease muscle strength by 8 percent—and studies show that two weeks of rehabilitation exercises did not help people rebuild their muscle strength. What’s more, in addition to its impact on muscle mass and function, reducing steps to between 1,000 to 1,500 steps per day has been shown to raise blood sugar and increase inflammation.

The researchers suggested that strategies to reduce the potential unhealthy effects of isolation are important. Resistance exercise is a classic and proven method to increase muscle mass, strength, and mobility, even for people in their 90s. Exercise programs you can do at home are especially important during isolation, and are a good way to maintain or even improve your muscle health and mobility. Exercise also helps prevent falls, a common cause of disability and hospitalization for older adults.

The researchers suggested that health education for older adults should include recommendations to introduce light activity into daily routines, focusing on sitting less and moving more, which is particularly important for people with mobility issues.

Good ways to work in more movement include:

Interrupting prolonged sitting time by taking strolling or standing breaks (such as moving around during commercials while watching TV).
Performing light household chores like cleaning and gardening and enjoying leisure activities such as dancing or short-distance walking.
Joining family members in-person (when safe) or remotely by FaceTime or Zoom to stay active and gain emotional support.

HealthinAging.org, maintained by the American Geriatrics Society, offers helpful suggestions for getting the right amount of physical activity.

This summary is from “Risk of Increased Physical Inactivity during COVID-19 Outbreak for the Elderly: A Call for Actions.” It appears online ahead of print in the Journal of the American Geriatrics Society. The study authors are Hamilton Roschel, PhD; Guilherme G. Artioli, PhD; and Bruno Gualano, PhD.

Journal

Journal of the American Geriatrics Society

DOI

10.1111/jgs.16550

Image: https://docs.google.com/document/d/1cpdYrtjo6mLDF5YCxmGmfyyKosNnrRfRefyaZWHyK8c/edit

Video: https://www.youtube.com/watch?v=GRT7FF2eVwU

A new robotic prosthetic leg prototype offers a more natural gait while also being quieter and more energy efficient than other designs.

The key is the use of new small and powerful motors, originally designed for a robotic arm on the International Space Station. The streamlined design offers a free-swinging knee and regenerative braking, which charges the battery with energy captured when the foot hits the ground. This feature enables the leg to more than double a typical prosthetic user's walking needs with one charge per day.

"Our prosthetic leg consumes approximately half the battery power of state-of-art robotic legs, yet can produce more force," said Robert Gregg, an associate professor of electrical and computer engineering at the University of Michigan and a member of the U-M Robotics Institute, who led the study while at the University of Texas at Dallas. Gregg moved to U-M last year.

Using conventional prosthetics, amputees must raise their hips to lift the prosthetic foot from the floor and swing the leg forward. This unnatural gait takes more energy than ordinary walking, causes extra stress and pain in the hips and lower back, and eventually damages the joints. Robotic legs have the potential to provide a much more comfortable gait, but one of their drawbacks is stiffness in the joints.

"We designed our joints to be as compliant, or flexible, as possible," said Toby Elery, first author of the study and recent doctoral graduate from UT Dallas. "Our robotic leg can perform and even react like a human joint would, enabling a naturally free-swinging knee and shock absorption when contacting the ground."

Motors in robotic legs need to fit into the space that an ordinary limb would take up. In the past, this has meant using small motors that spin quickly, and then using a series of gears to convert the fast spin into a more powerful force.

The problem is that the gears are noisy, inefficient, add weight and make it harder for the joints to swing. Gregg's group surmounted this by incorporating two of those stronger space station motors, one powering the knee and the other powering the ankle.

There are many benefits to using fewer gears. In addition to enabling the free-swinging knee, removing gears brought the noise level down from the scale of a vacuum cleaner to a refrigerator. Also, the regenerative braking absorbs some of the shock when the prosthetic foot hits the ground.

"If the joints are stiff or rigid, the force is transferred to the residual limb, and that can be painful," Gregg said. "Instead, we use that force to charge the battery."

The amputees who test drive the prosthetics in Gregg's lab say they can feel the leg helping them push off the ground as they walk.

"In some cases, they have observed that they feel like muscles in their hips and back are working less with our leg, compared to their conventional leg," Gregg said. "We're able to reduce compensations at the hips."

The team's next step is to improve the control algorithms that can help the leg automatically adjust to different terrain, changes in pace and transitions between different types of activity.

Wouldn't we all appreciate a little help around the house, especially if that help came in the form of a smart, adaptable, uncomplaining robot? Sure, there are the one-trick Roombas of the appliance world. But MIT engineers are envisioning robots more like home helpers, able to follow high-level, Alexa-type commands, such as "Go to the kitchen and fetch me a coffee cup."

To carry out such high-level tasks, researchers believe robots will have to be able to perceive their physical environment as humans do.

"In order to make any decision in the world, you need to have a mental model of the environment around you," says Luca Carlone, assistant professor of aeronautics and astronautics at MIT. "This is something so effortless for humans.

But for robots it's a painfully hard problem, where it's about transforming pixel values that they see through a camera, into an understanding of the world."
Now Carlone and his students have developed a representation of spatial perception for robots that is modeled after the way humans perceive and navigate the world.

The new model, which they call 3D Dynamic Scene Graphs, enables a robot to quickly generate a 3D map of its surroundings that also includes objects and their semantic labels (a chair versus a table, for instance), as well as people, rooms, walls, and other structures that the robot is likely seeing in its environment.

The model also allows the robot to extract relevant information from the 3D map, to query the location of objects and rooms, or the movement of people in its path.

"This compressed representation of the environment is useful because it allows our robot to quickly make decisions and plan its path," Carlone says. "This is not too far from what we do as humans. If you need to plan a path from your home to MIT, you don't plan every single position you need to take. You just think at the level of streets and landmarks, which helps you plan your route faster."

Beyond domestic helpers, Carlone says robots that adopt this new kind of mental model of the environment may also be suited for other high-level jobs, such as working side by side with people on a factory floor or exploring a disaster site for survivors.

He and his students, including lead author and MIT graduate student Antoni Rosinol, will present their findings this week at the Robotics: Science and Systems virtual conference.

A mapping mix

At the moment, robotic vision and navigation has advanced mainly along two routes: 3D mapping that enables robots to reconstruct their environment in three dimensions as they explore in real time; and semantic segmentation, which helps a robot classify features in its environment as semantic objects, such as a car versus a bicycle, which so far is mostly done on 2D images.

Carlone and Rosinol's new model of spatial perception is the first to generate a 3D map of the environment in real-time, while also labeling objects, people (which are dynamic, contrary to objects), and structures within that 3D map.

The key component of the team's new model is Kimera, an open-source library that the team previously developed to simultaneously construct a 3D geometric model of an environment, while encoding the likelihood that an object is, say, a chair versus a desk.

"Like the mythical creature that is a mix of different animals, we wanted Kimera to be a mix of mapping and semantic understanding in 3D," Carlone says.

Kimera works by taking in streams of images from a robot's camera, as well as inertial measurements from onboard sensors, to estimate the trajectory of the robot or camera and to reconstruct the scene as a 3D mesh, all in real-time.

To generate a semantic 3D mesh, Kimera uses an existing neural network trained on millions of real-world images, to predict the label of each pixel, and then projects these labels in 3D using a technique known as ray-casting, commonly used in computer graphics for real-time rendering.

The result is a map of a robot's environment that resembles a dense, three-dimensional mesh, where each face is color-coded as part of the objects, structures, and people within the environment.

A layered scene

If a robot were to rely on this mesh alone to navigate through its environment, it would be a computationally expensive and time-consuming task. So the researchers built off Kimera, developing algorithms to construct 3D dynamic "scene graphs" from Kimera's initial, highly dense, 3D semantic mesh.

Scene graphs are popular computer graphics models that manipulate and render complex scenes, and are typically used in video game engines to represent 3D environments.

In the case of the 3D dynamic scene graphs, the associated algorithms abstract, or break down, Kimera's detailed 3D semantic mesh into distinct semantic layers, such that a robot can "see" a scene through a particular layer, or lens. The layers progress in hierarchy from objects and people, to open spaces and structures such as walls and ceilings, to rooms, corridors, and halls, and finally whole buildings.

Carlone says this layered representation avoids a robot having to make sense of billions of points and faces in the original 3D mesh.

Within the layer of objects and people, the researchers have also been able to develop algorithms that track the movement and the shape of humans in the environment in real time.

The team tested their new model in a photo-realistic simulator, developed in collaboration with MIT Lincoln Laboratory, that simulates a robot navigating through a dynamic office environment filled with people moving around.

"We are essentially enabling robots to have mental models similar to the ones humans use," Carlone says. "This can impact many applications, including self-driving cars, search and rescue, collaborative manufacturing, and domestic robotics.

Another domain is virtual and augmented reality (AR). Imagine wearing AR goggles that run our algorithm: The goggles would be able to assist you with queries such as 'Where did I leave my red mug?' and 'What is the closest exit?'

You can think about it as an Alexa which is aware of the environment around you and understands objects, humans, and their relations."

"Our approach has just been made possible thanks to recent advances in deep learning and decades of research on simultaneous localization and mapping," Rosinol says. "With this work, we are making the leap toward a new era of robotic perception called spatial-AI, which is just in its infancy but has great potential in robotics and large-scale virtual and augmented reality."

Boston, MA -- More than 3 million people in the United States have been infected with COVID-19 and more than 130,000 have died. More people have died of COVID-19 in the U.S. than in any other country, but few studies offer national data on the factors that may contribute to outcomes for critically ill patients. To address this gap, investigators from more than 65 sites across the country, led by a team from Brigham and Women's Hospital, conducted the Study of the Treatment and Outcomes in critically ill Patients with COVID-19 (STOP-COVID), a multicenter cohort examination of the demographics, comorbidities, organ dysfunction, treatment, and outcomes of patients with COVID-19 admitted to intensive care units. The team studied over 2,000 critically ill adults with COVID-19, and found that 35 percent of patients died in the 28 days after ICU admission. They also found that treatment and outcomes varied greatly between hospitals. Results of their work are published in JAMA Internal Medicine.

"The U.S. is currently the epicenter of COVID-19, yet few national data are available on the epidemiologic factors, treatments, and outcomes of critically ill patients with COVID-19 in the U.S.," said corresponding author David E. Leaf, MD, MMSc, an associate physician in the Division of Renal Medicine at the Brigham. "We found that critically ill patients with COVID-19 have a greater than 1-in-3 chance of short-term death. We also found that treatment and outcomes varied considerably between hospitals, with a death rate more than three-fold higher in patients admitted to hospitals with fewer ICU beds."

The multicenter cohort study included Brigham and Women's Hospital and 64 other sites from the Northeast, South, Midwest and West regions of the U.S., including parts of the U.S. that were heavily affected by COVID-19. The study included 2,215 adults with laboratory-confirmed COVID-19 who were admitted to ICUs between March 4 and April 4, 2020.

Overall, 784 patients (35 percent) died within 28 days, with wide variation among hospitals. Factors independently associated with death included older age, male sex, higher body mass index, coronary artery disease, active cancer, and the presence of low oxygen levels, liver dysfunction, and kidney dysfunction at the time of ICU admission.

Even after adjusting for a variety of risk factors, death rates varied widely across hospitals, from 6 percent to 80 percent. The number of pre-COVID ICU beds in the hospital was strongly associated with death rate. Patients admitted to hospitals with less than 50 ICU beds had a more than three-fold higher risk of death than patients admitted to hospitals with 100 or more ICU beds.

In addition, hospitals varied widely in the proportion of patients who received medications and supportive therapy for COVID-19. During the time period studied, hydroxychloroquine, azithromycin, and anticoagulants were commonly prescribed, and interventions such as prone positioning were also being implemented. But the proportion of patients receiving these measures varied considerably -- for instance, the use of prone positioning ranged from 4 percent of patients at one hospital to 80 percent at another.

While the team adjusted for a large number of demographic and severity of illness characteristics, its estimates of differences in death rates across hospitals may be impacted by other confounders, such as the socioeconomic status of patients -- a risk factor increasingly recognized as important in health outcomes for COVID-19 patients. The team's models also do not account for varying degrees of strain across hospitals.

"This is the largest nationwide study of patients with COVID-19 admitted to ICUs across geographically diverse sites in the U.S.," said lead author Shruti Gupta, MD, MPH, a physician in the Brigham's Renal Division. "These are the patients with the highest mortality. Our study confirms that certain factors, such as older age and higher BMI, are associated with an increased risk of death. We also identified several novel risk factors for death, such as treatment at a hospital with fewer ICU beds. That's one of the most intriguing findings from our work, which, along with many other questions, we'll be pursuing in the future."

To catch a thief, the saying goes, you have to think like a thief. The same is true for invasive predators: to foil their depredations on native wildlife, scientists have to understand how they think.

A new study published in the Ecological Society of America's journal Ecological Applications examines how invasive mammalian predators both habituate to and generalize avian prey cues. Dr. Price and her team at Manaaki Whenua Landcare Research studied the behavior of ferrets and hedgehogs--invasive mammals in New Zealand--in an outdoor enclosure experiment to understand how they hunt avian prey. The discovery could have conservation applications for protecting native bird species.

Previous research has established that "chemical camouflage" could be an effective way to deter invasive species from harming vulnerable bird populations: scientists can distribute appealing bird odors near nests before eggs appear, so that the predator eventually starts ignoring the smell--even after tasty eggs become available.

This study goes a step further, showing that invasive predators not only learn to pinpoint (or ignore) certain smells that are associated with food--they can also classify similar smells into groups.

"We are trying to understand how these predators have been so effective at destroying the native fauna," says Catherine Price, a postdoctoral research associate at the University of Sydney and the study's lead author. "We are researching new ways to exploit behavioral patterns and traits to understand why native species are so vulnerable and how to protect them."

In New Zealand, invasive mammalian predators have devastated local bird populations, especially of the wrybill, double-banded plover, kak?, and black-fronted tern, whose populations nest at the same time and in similar locations. Such nesting colonies are the proverbial sitting duck: with no defenses, small numbers of predators like ferrets and hedgehogs can essentially wipe out nearly a generation with very little effort.

Hedgehogs and ferrets are generalists. Ferrets mainly hunt rabbits but will not turn down an easy meal of eggs or chicks. Hedgehogs eat mostly invertebrates and berries but also love eggs, especially right out of hibernation when they are especially hungry.

Price wanted to understand how the predators seek out bird colonies. While humans are primarily visual, many other animals--including ferrets and hedgehogs--draw more information from other senses, including their sense of smell.

"Because humans aren't olfactory species, we don't often think about odor," Price said. "But these predators are very sensitive to odor, and to the costs of odor. They respond very quickly if a hunting tactic--like following a certain odor--isn't working."

Price and her team captured local ferrets and hedgehogs and ran them through a series of controlled treatments in outdoor enclosures resembling their natural habitat to examine how these predators categorize smells--whether they group smells of similar types of birds together--and how and whether they habituate to smells. This is the first time this kind of research has been done on these predators in a controlled outdoor setting.

The question of categorization reveals a substantial amount about the hunting strategies and priorities of the predator. Separating smells into individual species requires an investment that might not always be merited. In some cases, it is sufficient for ferrets or hedgehogs to simply sniff out a broad category of prey, such as "ground-nesting bird with eggs this time of year," but knowing exactly what kind of bird they are smelling is irrelevant.

"The idea that animals are grouping prey together by smell is exciting," Price said. "We never assumed wild animals did that before, and now we've shown that they can do this using smell."

The team discovered that ferrets generalized the avian smells (in this case gulls and quail) but the hedgehogs did not. In many ways, this makes sense: ferrets consume lots of prey besides bird species, so distinguishing between bird smells may not be worth a ferret's time or energy. Seasonality may also have played a role. In the experiment, hedgehogs were getting ready to go into hibernation, making them especially motivated to find high-quality meals easily.

This finding indicates it might be possible to protect bird colonies by distributing bird smell around the area. If an entire area were saturated with the smell of a nesting ground species, it could protect a nesting colony. Predators would become accustomed to the smell and ignore it, seeking out other prey.

"Understanding how predators group smell is important because if they generalize, we don't have to actually put out the smell of the bird we're protecting; we can put out chicken or quail odors that we can easily get in abundance," Price said.

Understanding how invasive predators hunt and think gives scientists and conservationists an edge in protecting native prey. Further studies may reveal more ways to protect native populations by exploiting predators' behaviors.

Plants have to interpret temperature fluctuations over timescales ranging from hours to months to align their growth and development with the seasons.

Much is known about how plants respond to temperature but the mechanisms that allow them to measure the temperature signal are less well understood.

In this study which appears in Nature, researchers Yusheng Zhao and Rea Antoniou-Kourounioti in the groups of Professor Dame Caroline Dean and Professor Martin Howard at John Innes Centre show that slow growth is used as a signal to sense long-term changes in temperature.

"We have found a new temperature sensing mechanism that holds a long-term memory of the cold, integrating over fluctuating temperatures to measure cold duration. This is a new type of physical mechanism for temperature-sensing and can guide further studies in this area" explains first author Dr Yusheng Zhao.

Using a forward genetic screen - looking at the genetics of plants showing a particular trait - they found a dysfunctional response. These plants showed high levels of a protein called VIN3 in warm temperatures. This protein is well known as being upregulated during periods of cold and interacts with the epigenetic molecular memory system that allows plants to remember cold.

Dr Yusheng Zhao found these plants had one of two versions of mutated NTL8, a transcription factor or regulator protein that activated VIN3 even without cold.

To understand the role of NTL8 they tagged it with a fluorescent protein (GFP) and looked with help from the Bioimaging platform at the John Innes Centre to show where this protein is present compared to VIN3. This showed that the mutated version was found everywhere in the plant and the wild type protein was mostly observed in the growing tips of roots. It also showed that it accumulates slowly over time in the cold.

Using a theoretical approach to explore the problem further, the team reasoned that understanding how fast the NTL8 protein degrades may offer insight into how the slow dynamics of NTL8 and VIN3 operate. They discovered the NTL8 protein is long-lasting, as predicted by the theory.

Mathematical modelling showed that the main factor determining the amount of NTL8 protein is growth dependent dilution. If the weather gets warmer, the plants grow quicker and as cells multiply, the amount of NTL8 becomes diluted. In contrast, in cooler temperatures plants grow more slowly and NTL8 is more concentrated, being able to accumulate over time. The mathematical model can reproduce the observations of NTL8 protein levels seen in the warm and cold.

To further test the model, they added chemicals and hormones to change plant growth to see if this changed the levels of NTL8 as predicted by the model, which it did. In the roots they added the plant growth hormone Gibberellin, which causes plants to grow faster and NTL8 levels were lower, as expected. When they added an inhibitor of growth, NTL8 protein levels were higher in the whole plant. The team did similar experiments on the roots, and these predictions were confirmed too.

Dr Rea Antoniou-Kourounioti joint first author adds: "We were surprised by the simplicity of the new temperature mechanism we discovered, which recycles temperature information from one process [growth] to create a completely new temperature sensing mechanism for another [vernalization - the acceleration of flowering by cold]. We could reproduce most of the temperature-dependent changes in our experimental observations with our model by just changing the growth rate between warm and cold."

"This study revolutionises our understanding of how temperature is sensed by plants, and particularly how fluctuating long-term environmental conditions are integrated," says Professor Martin Howard.

"This study shows the fantastic synergy when experimental approaches are combined with computational modelling. We would never have figured out this mechanism by doing either separately," says Caroline Dean.

The findings will be useful for understanding how plants as well as other organisms sense the long-term fluctuating environmental signals and could apply to crops.

Washington, DC - July 15, 2020 - Metabolic syndrome increases the risk of severe disease from viral infection, according to a review of the literature performed by a team of researchers from St. Jude Graduate School of Biomedical Sciences and the University of Tennessee Health Science Center, both in Memphis. The research appears this week in the Journal of Virology, a publication of the American Society for Microbiology.

Metabolic syndrome is a cluster of at least 3 co-occurring conditions that raise the risk of heart disease, stroke and type 2 diabetes mellitus (T2DM). These conditions include excess abdominal fat, high blood pressure, excess blood sugar, abnormalities of lipids (including excess triglycerides and cholesterol), insulin resistance and a proinflammatory state.

Multiple studies have shown that obesity is associated with increased severity of influenza A, higher viral titers in exhaled breath and prolonged transmission of the virus, according to the report. Changes in the viral population may abet the emergence of more pathogenic influenza variants, according to the report. Despite the fact that influenza vaccines generate robust antibody titers in obese subjects, obesity doubles the likelihood of developing influenza.

As with influenza virus, the Centers for Disease Control and Prevention recently recognized obesity as a risk factor for severe illness caused by SARS-CoV-2. "This is not surprising because excess body weight and fat deposition apply pressure to the diaphragm, which further increases the difficulty of breathing during a viral infection," the researchers write.

But the risk goes beyond the burden of excess weight. A recent study highlighted in the literature review looked at 174 diabetes patients with confirmed cases of COVID-19. The study found that these patients were at significantly higher risk for severe pneumonia compared to non-diabetic COVID-19 patients. CT scans revealed a greater severity of lung abnormalities in these patients.

There was also a profound increase in serum IL-6 levels, a predictive biomarker for disease severity, the investigators write. These data imply that SARS-CoV-2 causes severe disease in obese patients and in those with T2DM by inducing bilateral pneumonia and a cytokine storm that damages the lung epithelial-endothelial barrier. (The epithelium lines surfaces exposed to the outer environment, such as the respiratory tract, the endothelium lines inner pathways such as those of the vasculature.)

However, one hypothetical risk for patients with T2DM who have hypertension or heart disease appears not to be a problem, after all, according to the report. These patients are commonly treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These increase expression of ACE2, the receptor that SARS-CoV-2 uses to gain entry into cells.

Clinicians and researchers were initially concerned that ACE inhibitors and ARBs could promote adhesion and entry of SARS-CoV-2 into host cells, thereby increasing the risk of severe COVID-19. Contrary to concerns, multiple studies now suggest that ACE inhibitors and ARBs do not lead to poorer outcomes in COVID-19 infection.

"Future research should seek to [determine] how metabolic abnormalities increase viral pathogenesis, as this information will play an essential role in global preparedness against emerging seasonal and pandemic virus strains," the investigators conclude.

ASM is keeping the pulse on the SARS-CoV-2 pandemic with the COVID-19 Research Registry of top-ranked research articles curated by experts. In the eye of a pandemic, this curated database will ensure that scientists, journalists and the public have an efficient way to find the timeliest and most valuable SARS-CoV-2/COVID-19 research from the latest journal articles and preprints.

The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.

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Journal

Journal of Virology

Nuclear magnetic resonance (NMR) is employed in a wide range of applications. In chemistry, nuclear magnetic resonance spectroscopy is in standard use for the purposes of analysis, while in the medical field, magnetic resonance imaging (MRI) is used to see structures and metabolism in the body. Scientists at Johannes Gutenberg University Mainz (JGU) and the Helmholtz Institute Mainz (HIM), working in collaboration with visiting researchers from Novosibirsk in Russia, have developed a new method of observing chemical reactions. For this purpose they use NMR spectroscopy, but with an unusual twist: There is no magnetic field. "This technique has two advantages. For a start, we are able to analyze samples in metal containers and, at the same time, we can examine more complex substances made up of different types of components," said Professor Dmitry Budker, head of the Mainz-based group. "We think our concept could be extremely useful when it comes to practical applications."

As a chemical technique, NMR spectroscopy is used to analyze the composition of substances and to determine their structures. High-field NMR is frequently used, which allows the nondestructive examination of samples. However, this method cannot be used to observe chemical reactions in metal containers because the metal acts as a shield, preventing penetration of the relatively high frequencies. For this reason, NMR sample containers are typically made of glass, quartz, plastic, or ceramic. Furthermore, high-field NMR spectra of heterogeneous samples containing more than one component tend to be poor. There are more advanced concepts but these often have the drawback that they do not make in situ monitoring of reactions possible.

Use of zero- to ultralow-field magnetic resonance proposed as a solution

The team led by Professor Dmitry Budker has thus proposed the use of zero- to ultralow-field nuclear magnetic resonance, ZULF NMR for short, in order to circumvent the problems. In this case, due to the absence of a strong external magnetic field, a metal container will not have a screening effect. The research group used a titanium test tube and a conventional glass NMR test tube for comparison in their experiments. In each case, para-enriched hydrogen gas was bubbled into a liquid to initiate a reaction between its molecules and the hydrogen.

The results showed that the reaction in the titanium tube could be readily monitored using ZULF NMR. It was possible to observe the kinetics of the ongoing reaction with high spectroscopic resolution while continually bubbling parahydrogen gas. "We anticipate that ZULF NMR will find application in the field of catalysis for operando and in situ reaction monitoring as well as in the study of chemical reaction mechanisms under realistic conditions," write the researchers in their article published in the leading scientific journal Angewandte Chemie International Edition. Three researchers from the International Tomography Center in Novosibirsk were also involved in the project, namely Professor Igor V. Koptyug, a visiting scholar at HIM in Mainz, Dudari B. Burueva, a doctoral candidate of Koptyug who was also a visiting scholar and a joint first author of the now published study, and Dr. Kirill V. Kovtunov. "Sadly, our colleague Kirill Kovtunov passed away during the preparation of the manuscript for this publication. His contributions were very important to us," acknowledged Professor Dmitry Budker. Furthermore, a group of young scientists from HIM and JGU collaborated in the research project, namely joint first author Dr. James Eills, and Dr. John W. Blanchard, along with doctoral candidates Antoine Garcon and Román Picazo Frutos.

PHILADELPHIA -- Researchers from the Penn Institute of Immunology discovered three distinct immune responses to the SARS-CoV2 infection that could help predict the trajectory of disease in severe COVID-19 patients and may ultimately inform how to best treat them.

The findings were published in Science.

"For patients who are hospitalized with COVID-19, there isn't just one way for the immune system to respond. There's a lot of heterogeneity, which we've distilled down into what we're calling three "immunotypes," said senior author E. John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania. "We're hopeful we may actually be able to predict, or at least infer, the different immune patterns a patient has based on clinical data. This would allow us to start thinking about enrolling patients to different types of clinical trials investigating treatments."

The coronavirus triggers different immune responses and symptoms in critically ill patients, but how those two correspond has remained poorly understood, making treatment decisions more difficult.

While recent studies reveal details on the immune's response to the virus, most have been single-case reports or focused on a small group of individuals. This is the first study, to the author's knowledge, to offer up a comprehensive immune profile of a large number of hospitalized patients.

The researchers applied deep immune profiling to capture individual responses of 163 patients during the course of their infections. The study included 90 hospitalized patients treated at the Hospital of the University of Pennsylvania, 29 non-hospitalized patients, and 44 healthy donors with no COVID-19 infection. The immune responses varied among the group, but there were patterns that hold clinical promise.

The first immunotype had robust CD4+ T cell activity, with modest activation of CD8+ T cells and peripheral blood lymphocytes. CD4+ and CD8+ act as the main inflammatory immune cells that work to clear viruses. The second immunotype was characterized mainly by a subset of CD8+ T cells known as EM and EMRA and a modest activation of CD8+ T cells, memory B cells, and peripheral blood lymphocytes. The third immunotype showed little to no evidence of an immune response to the infection.

Next, researchers combined the profiling with clinical data to understand the relationships between immune responses and disease. The first immunotype was tied to more severe disease that included inflammation, organ failure, and acute kidney disease. The second correlated not with disease severity but instead pre-existing immunosuppression and mortality. The third type, which had no immune activation, was not associated with specific symptoms or clinical features, though they varied.

The immunotypes developed by Wherry and team represent adaptive immune responses. A second study from researchers at Penn, published in Science Immunology, uncovered new details about the innate, or initial, response to SARS-CoV2.

"T and B cell activity are informed by innate immune responses," said senior author Michael R. Betts, PhD, a professor of Microbiology and program leader in the Penn Institute of Immunology, who is also a co-author on the first study. "We believe what's happening with the innate response of the immune system might be what's leading to these three immune phenotypes Dr. Wherry's lab identified."

Profiling the blood samples of 42 infected patients (with moderate and severe disease) and 12 healthy donors, the researchers found a similar heterogeneity in immune adaptive responses: robust activation of CD4+ and CD8+ T cells, B cells, along with peripheral blood cells, like neutrophils, monocytes, and "natural killer," or NK, cells.

While the innate responses were also heterogenous, the researchers observed a decrease of CD15 and CD16 molecules on neutrophils and CD16 on NK cells, immature granulocytes, and monocytes, in patients with more severe disease. These two molecules are known players in the immune's response to viral infections that also represent a potential target for immunotherapy. How they are driving and exacerbating the adaptive responses in the three immunotypes is an important question the labs are working to better understand.

COVID-19 studies have been moving at an unprecedented speed as researchers band together to find answers. Among its many efforts, Penn formed lab and clinical research teams from diverse backgrounds to strengthen its focus on the immune system, along with the COVID Processing Unit to manage specimens to profile.

"Understanding the power of the immune system to regulate responses to disease is one of the major advances in medicine in the last decade, and Penn has been at the center leading that discovery. We are now applying the broad expertise and experience of our more than 200-person immunology community toward the research and treatment of COVID-19," said Jonathan A. Epstein, MD, executive vice dean, chief scientific officer, and a professor of Cardiovascular Research at Penn. "The deep immuno-profiling work the investigators applied here is likely to be useful not only now, for this disease, but into the future for many others."

An analysis of immune responses in 42 COVID-19 patients, both infected and recovered, identified immune signatures that distinguish severe COVID-19 cases. Notably, the analysis features insights not only into adaptive immune cell responses, but also those of innate immune cells responding to the virus. The findings will inform development of COVID-19 therapeutics. As the global COVID-19 pandemic continues, knowledge of the immunological signatures of severe COVID-19 is continually evolving. Whether there is a common profile of immune dysfunction in critically ill COVID-19 patients remains a question. To date, studies investigating this are limited, reporting on single patients or small cohorts. Seeking to expand upon them, Leticia Kuri-Cervantes and colleagues - a group overlapping in part with authors of the study by Mathew et al. published in Science today (15 July, 2020) - performed a high dimensional flow cytometry analysis on immune cells in blood from 42 COVID-19 patients with varying levels of disease state (moderate, severe, and recovered). Consistent with previous reports, they identified (and further defined) a characteristic immune phenotype in severe COVID-19 patients - distinct from the response in both healthy donors and also in COVID-19 patients with moderate or recovered disease. They also uncovered changes in the innate immune system - circulating neutrophils, monocytes and natural killer cells - in severe COVID-19 patients, though whether these are a "consequence or contributing factor towards COVID-19 severity remains to be defined," they say. The authors suggest the immune dysregulation they observed in severe COVID-19 patients "may necessitate targeted strategies to effectively manage clinical care" for this group. Longitudinal studies will be needed, they say, to determine whether early detection of these immunological perturbations predict severe disease trajectory in patients who are asymptomatic or have mild disease.

Expanding on observations made in smaller patient cohorts, researchers studying immune responses of 125 hospitalized COVID-19 patients identified distinct immune profiles -- "Immunotypes" -- and showed how these signatures correlated with disease severity. "By localizing patients on an immune topology map," Divij Mathew and colleagues say, "we can begin to infer which types of therapeutic interventions may be most useful in specific patients." As the global COVID-19 pandemic continues, researchers continue to investigate the characteristics of the human immune response in fighting it. Whether there is a common profile of immune dysfunction in critically ill COVID-19 patients remains a question. To date, studies investigating this are limited, reporting on single patients or small cohorts. Seeking to expand upon them, and also to better connect immune features in COVID-19 patients with clinical features of disease, Mathew and colleagues performed a high dimensional flow cytometry analysis on immune cells in blood from 125 COVID-19 patients at two points during their first week of hospitalization. Mathew and colleagues also collected clinical data on their patient cohort. Combining the flow cytometric and clinical data, they report several key findings, including that a defining feature of COVID-19 disease in this group is variability in immune response. At the same time, they found certain stable immune response signatures in subsets of their patients, which changed over time in consistent ways. Some of these patterns, like impaired CD8 T cell activation, were associated with worse disease outcomes. Mathew et al. ultimately defined three immune response signatures, or Immunotypes, in this cohort, associated with poor clinical trajectories versus improving health. "These Immunotypes may reflect fundamental differences in the ways patients respond to SARS-CoV2 infection," they say. They note that their "findings provoke the idea of the tailoring clinical treatments or future immune-based clinical trials to patients whose immunotype suggests greater potential benefit."

DALLAS, July 15, 2020 -- People who are homeless may experience 60-70% higher rates of cardiovascular events, such as heart attacks, strokes and heart failure, compared to the general population, according to a study cited in "The Importance of Housing and Cardiovascular Health and Well-Being," a new Scientific Statement from the American Heart Association published today in the Association's journal Circulation: Cardiovascular Quality and Outcomes.

The statement reviews and summarizes current research about how housing stability, safety, affordability, lack of access to high-quality housing and neighborhood environment affect cardiovascular disease risk. Homelessness is defined by the U.S. Department of Housing and Urban Development as the inability to obtain permanent housing. This includes serial renters who move often, people who temporarily live in a hotel, homeless shelter or with friends, and those living on the street.

Housing is one of several social determinants that impact cardiovascular health. Additional social determinants of health include socioeconomic factors, such as lack of education, unemployment or under-employment, and access to health care, among others.

"The disparities in cardiovascular health among people who are homeless and marginally housed are largely due to psychosocial stressors, unhealthy behaviors used as coping mechanisms and barriers to health care, including lack of insurance and stigmatization among this population," said Mario Sims, Ph.D., M.S., FAHA, chair of the writing group for the scientific statement, chief science officer of the Jackson Heart Study and professor in the department of medicine at the University of Mississippi Medical Center in Jackson, Mississippi.

"Chronic housing insecurity may impact a person's ability to eat properly, get quality sleep, schedule regular medical care or fill prescriptions due to cost. These factors all contribute to inadequate treatment to reduce cardiovascular risk factors such as high blood pressure, high cholesterol and tobacco use, and to the greater likelihood of having a cardiovascular event such as a heart attack or stroke," said Sims.

Among adults who were homeless and housing insecure:

70-80% smoke cigarettes, and smoking is attributed to 60% of CVD deaths in this population;

25% report recent cocaine use, which increases risk of heart attack; and

25% have mental illness, which may contribute to delayed diagnosis and fragmented medical care.

Poor housing quality - including structural deterioration, insufficient heating/cooling and exposure to cardiotoxic pollutants such as mold, lead or secondhand smoke - impacts cardiovascular disease risk factors. Studies have found that adults who live in older, public or low-income housing are more likely to have cardiovascular disease. Substandard living conditions affect mental health, which is also associated with heart and blood vessel health in both children and adults. Improving air quality, reducing dampness and living in a comfortable temperature have been shown to lower blood pressure.

Residential segregation by race and ethnicity as well as gentrification have further affected cardiovascular health by making it harder for more individuals to find affordable, high-quality housing. Gentrification is the process of revitalizing a deteriorating neighborhood, with affluent people displacing lower-income residents.

The 2007-2010 foreclosure crisis also had a substantial effect on housing accessibility. Multiple studies found an association between foreclosures and poorer cardiovascular health, with significant differences among races. Hispanics in residential areas at risk for foreclosure had higher rates of high blood pressure and high cholesterol. Foreclosures were also associated with higher rates of heart attacks and strokes among middle-aged Black residents.

"Neighborhood environments are strong predictors of cardiovascular health and well-being," said Sims. "Studies have consistently shown that individuals residing in economically distressed neighborhoods with high poverty and unemployment rates have a higher incidence of cardiovascular risk factors, including obesity, diabetes, hypertension and heart disease, and higher risk of stroke and death from a cardiovascular disease such as heart attacks, strokes, heart failure and others."

Urban design features, such as an area's walkability and accessibility to healthy food options, are associated with body mass index (a way to measure body weight), blood pressure, type 2 diabetes and metabolic syndrome (a cluster of risk factors that include high blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol or triglyceride levels). Research suggests that neighborhood greenness, or vegetation, may also be beneficial for cardiovascular health. Higher levels of greenness are also associated with lower rates of type 2 diabetes, heart attack, coronary artery disease and heart failure.

Providing equitable housing opportunities may improve cardiovascular health, and efforts to reduce health disparities should consider multi-level housing interventions, particularly for under-resourced communities, according to the writing group.