Culture

As COVID-19 spreads across the globe, a common question is, can infectious diseases be connected to environmental change? Yes, indicates a study published today from the University of California, Davis' One Health Institute.

Exploitation of wildlife by humans through hunting, trade, habitat degradation and urbanization facilitates close contact between wildlife and humans, which increases the risk of virus spillover, found a study published in the journal Proceedings of the Royal Society B. Many of these same activities also drive wildlife population declines and the risk of extinction.

The study provides new evidence for assessing spillover risk in animal species and highlights how the processes that create wildlife population declines also enable the transmission of animal viruses to humans.

"Spillover of viruses from animals is a direct result of our actions involving wildlife and their habitat," said lead author Christine Kreuder Johnson, project director of USAID PREDICT and director of the EpiCenter for Disease Dynamics at the One Health Institute, a program of the UC Davis School of Veterinary Medicine. "The consequence is they're sharing their viruses with us. These actions simultaneously threaten species survival and increase the risk of spillover. In an unfortunate convergence of many factors, this brings about the kind of mess we're in now."

THE COMMON AND THE RARE

For the study, the scientists assembled a large dataset of the 142 known viruses that spill over from animals to humans and the species that have been implicated as potential hosts. Using the IUCN Red List of Threatened Species, they examined patterns in those species' abundance, extinction risks and underlying causes for species declines.

The data show clear trends in spillover risk that highlight how people have interacted with animals throughout history.

Among the findings:

Domesticated animals, including livestock, have shared the highest number of viruses with humans, with eight times more zoonotic viruses compared to wild mammalian species. This is likely a result of our frequent close interactions with these species for centuries.

Wild animals that have increased in abundance and adapted well to human-dominated environments also share more viruses with people. These include some rodent, bat and primate species that live among people, near our homes, and around our farms and crops, making them high-risk for ongoing transmission of viruses to people.

At the other end of the spectrum are threatened and endangered species. These are animals whose population declines were connected to hunting, wildlife trade and decreases in habitat quality. These species were predicted to host twice as many zoonotic viruses compared to threatened species that had populations decreasing for other reasons.

Threatened and endangered species also tend to be highly managed and directly monitored by humans trying to bring about their population recovery, which also puts them into greater contact with people. Bats repeatedly have been implicated as a source of "high consequence" pathogens, including SARS, Nipah virus, Marburg virus and ebolaviruses, the study notes.

"We need to be really attentive to how we interact with wildlife and the activities that bring humans and wildlife together," Johnson said. "We obviously don't want pandemics of this scale. We need to find ways to co-exist safely with wildlife, as they have no shortages of viruses to give us."

GAINESVILLE, Fla. --- The bright chirp of the coquí frog, the national symbol of Puerto Rico, has likely resounded through Caribbean forests for at least 29 million years.

A new study published in Biology Letters describes a fragmented arm bone from a frog in the genus Eleutherodactylus, also known as rain frogs or coquís. The fossil is the oldest record of frogs in the Caribbean and, fittingly, was discovered on the island where coquís are most beloved.

"It's a national treasure," said David Blackburn, Florida Museum curator of herpetology and the study's lead author. "Not only is this the oldest evidence for a frog in the Caribbean, it also happens to be one of the frogs that are the pride of Puerto Rico and related to the large family Eleutherodactylidae, which includes Florida's invasive greenhouse frogs."

Jorge Velez-Juarbe, associate curator of marine mammals at the Natural History Museum of Los Angeles County, found the fossil on a river outcrop in the municipality of San Sebastian in northwestern Puerto Rico. Velez-Juarbe and his collaborators' previous collecting efforts at the site uncovered fossil seeds, sea cows, side-necked turtles and the oldest remains of gharials and rodents in the Caribbean, dating to the early Oligocene Epoch, about 29 million years ago.

Still, "there have been many visits from which I have come out empty-handed over the last 14 years," he said. "I've always kept my expectations not too high for this series of outcrops."

On this trip in 2012, he combed the deposits for half a day without much luck when a small bone, partially exposed in the sediment, caught his eye. He examined it with his hand lens.

"At the moment, I couldn't wrap my mind as to what it was," Velez-Juarbe said. "Then once I got back home, cleaned around it with a needle to see it better and checked some references, I knew I had found the oldest frog in the Caribbean."

The ancient coquí displaces an amber frog fossil discovered in the Dominican Republic in 1987 for the title of oldest Caribbean frog. While the amber fossil was originally estimated to be 40 million years old, scientists now date Dominican amber to about 20 million to 15 million years ago, Blackburn said.

Based on genetic data and family trees, scientists had hypothesized rain frogs lived in the Caribbean during the Oligocene, but lacked any fossil evidence. The small, lightweight bones of frogs often do not preserve well, especially when combined with the hot, humid climate of the tropics.

Matching a single bone fragment to a genus or species "is not always an easy process," Velez-Juarbe said. It can also depend on finding the right expert. His quest for help identifying the fossil turned up empty until a 2017 visit to the Florida Museum where he had once been a postdoctoral researcher.

"I got to talk with Dave about projects, and the rest is now history," he said.

Possibly first arriving in the Caribbean by rafting from South America, frogs in the genus Eleutherodactylus, which encompasses some 200 species, dominate the region today.

"This is the most diverse group by two orders of magnitude in the Caribbean," Blackburn said. "They've diversified into all these different specialists with various forms and body sizes. Several invasive species also happen to be from this genus. All this raises the question of how they got to be this way."

One partial arm bone may not tell the whole story of coquí evolution - but it's a start.

"I am thrilled that, little by little, we are learning about the wildlife that lived in Puerto Rico 29-27 million years ago," Velez-Juarbe said. "Finds like this help us unravel the origins of the animals we see in the Caribbean today."

Italy was the main origin of the individuals who first brought the novel coronavirus to Brazil, according to a study by Brazilian researchers in collaboration with colleagues in the United Kingdom, Canada and the United States.

The COVID-19 pandemic arrived in Brazil between February and early March.

"In contrast with China and other countries, where the outbreak began slowly with a small number of cases, it was started in Brazil by more than 300 people, most of whom came from Italy. The virus spread very quickly as a result," said Ester Sabino, one of the authors of the study. Sabino is a professor at the University of São Paulo's Medical School (FM-USP) and headed the university's Institute of Tropical Medicine (IMT-USP) between 2015 and 2019.

Most of these people came from Italy to São Paulo City, where the first cases of the disease in Brazil were notified, but some went to other destinations, including Rio de Janeiro, Porto Alegre, Salvador, Curitiba, Belo Horizonte, Fortaleza, Recife, Vitória and Florianópolis, contributing to the nationwide spread of the disease.

The study was supported by São Paulo Research Foundation - FAPESP under the aegis of the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE). The results are reported in an article published in the Journal of Travel Medicine.

The researchers estimated that 54.8% of all cases of COVID-19 imported into Brazil by March 5 derived from people infected in Italy, followed by passengers who flew in from China (9.3%) and France (8.3%).

They also estimated that 24.9% of all infected people flying to Brazil during the period traveled from Italy to São Paulo, and that Italy was the start of five of the ten main routes for infected travelers coming to Brazil (via China, France, Switzerland, South Korea and Spain).

To identify the main routes for the importation of COVID-19 to Brazil, the researchers analyzed February-March 2020 data for passengers traveling to any Brazilian airport from 29 countries with confirmed cases of the disease.

They estimated the proportion of infected travelers potentially arriving in Brazilian cities from each country and for each route based on the total number of passengers flying to any Brazilian airport during the period, country populations and the number of cases notified by these countries as of March 5, 2020.

The estimates were corroborated by the Brazilian Ministry of Health's official data on notified cases, showing that 14 of the first 29 patients diagnosed with COVID-19 in Brazil had just been to Italy. Six of them (23.1%) were notified in São Paulo.

"It was very clear that São Paulo would be the epicenter of the epidemic in Brazil because it was the final destination for the largest number of infected people coming mainly from Italy," Sabino said.

Focus on internal mobility

According to Sabino, who led the genome sequencing of the coronaviruses isolated from the first two confirmed cases of COVID-19 in Brazil, sustained community transmission of the disease now prevails and the authorities should focus on restricting internal mobility in order to contain the epidemic.

This means restricting the mobility of the inhabitants of São Paulo, where most of the confirmed cases in Brazil have been notified.

"São Paulo and to a lesser extent Rio de Janeiro will be the hubs from which the virus spreads to the rest of the country, so people should be prevented from leaving these two cities," she said.

Continuation of sequencing

The researchers led by Sabino continue to sequence SARS-CoV-2 isolated from Brazilians diagnosed with COVID-19. At one point they had to stop because some of their members were thought to have been infected.

"We had to shut down the lab, but we're back now and will analyze whether we can sequence a larger number of viral genomes," Sabino said.

The speed with which the disease spread around Brazil has disrupted the group's plans. "Transmission of the virus is proceeding so fast that the sequencing data can't help us understand how the epidemic is spreading as we planned," Sabino said.

The researchers expected to be able to sequence viruses as sporadic cases of the disease were notified in order to keep track of the transmission trajectory and contribute to the design of a containment strategy, but the number of cases arriving at the lab simultaneously turned out to be too high.

"It won't be possible to control the epidemic with sequencing alone. It's spreading very fast, and we can no longer track all the cases," Sabino said.

The number of genomes sequenced worldwide from infected patients has almost reached 800. These sequences are being made public, and can be used for research on primary resistance to help develop promising antiviral drugs against the virus, Sabino explained.

"When a candidate drug is found, a database of viral genome sequences will certainly be useful for this purpose," she said.

WASHINGTON, April 7, 2020 -- In recent years, chaos theory and other forms of computational modeling have sought to leverage findings in the social sciences to better describe -- and maybe one day predict -- how groups of people behave. One approach looks to update a widely used model to examine how changes in political opinions ripple through a group and how polarization can arise.

In this week's Chaos, from AIP Publishing, researchers at the University of Edinburgh and the University of Central Florida use a theoretical model for how political opinions evolve in a population to examine what effect those with more extreme views have on making the entire system more polarized. The group's network-based model extends a popular approach for studying opinion dynamics, called the Cobb model, and is based on the hypothesis that those with opinions farther from the middle of a political spectrum are also less influenced by others, a trait known to social scientists as "rigidity of the extreme."

"We have laws to understand gravity or chemical kinetics, but people don't always behave rationally, and the laws are much more difficult to pin down," said author Desmond Higham. "So, it's a fascinating but somewhat slippery area to try to work in. Anything that adds to our understanding with a simple model that captures behavior is worth pursuing."

In the simplest version of the model, members of a society are arranged in a line, each of whom can sway the two on either side of them. Each simulated person is assigned a starting number between 0 and 1 that describes how strongly they initially aligned to either end of a hypothetical political spectrum.

"These kinds of effects occur in patches in society and can be difficult to identify," said author Alexander Mantzaris. "They can evolve in segments that grow over time."

The simulations produced periods of what the researchers called bistability, where most members of a simulated society chose two extreme, competing opinions. In simulations that randomly connected individuals, the pair found the potential for taking extreme sides happened more rapidly.

The researchers believe their work can help inform other work on networks outside of political opinion, such as understanding how wealth affects handling finances, how international policymakers influence each other and even how we affect each other's music tastes.

They hope to expand the model by using new types of connectivity structures and to apply real-world data.

WASHINGTON, April 7, 2020 -- Bottle emptying is a phenomenon most of us have observed while pouring a beverage. Researchers from the Indian Institute of Technology Roorkee discovered how to make bottles empty faster, which has wide-ranging implications for many areas beyond the beverage industry.

Bubbles have been studied extensively for centuries, including early efforts by Leonardo da Vinci who famously noted the sinusoidal rise of bubbles within a pool. The growth dynamics of bubbles at the mouth of a bottle depend on the thermophysical properties of the fluid, the bottle geometry and its angle of inclination. These inextricably intertwined parameters have made bottle-emptying dynamics the next frontier for bubble physicists.

In this week's Physics of Fluids, from AIP Publishing, Lokesh Rohilla and Arup Kumar Das explore this bottle-emptying phenomenon from the perspective of bubble dynamics on a commercial bottle by using high-speed photography. Image analysis allowed them to conceptualize various parameters, such as liquid film thickness, bubble aspect ratio, rise velocity and bottle emptying modes.

"Bubble dynamics inside the bottle are too complex to study, so we divided the bubble interfacial growth into different stages to comprehend them," said Rohilla.

It's well known that a bottle's emptying time is faster if you increase its angle of inclination. This increases what's known as bubble pinch off frequency, and the relative increment depends upon the thermophysical properties of the fluid.

"Our experiments suggest there is a critical angle of inclination, after which any further increase in the inclination of the bottle won't lead to further reduction in the bottle emptying time," said Rohilla. "This occurs due to the saturation of the voidage, space occupied by air within liquid surrounding, at the bottle's mouth with the angle of inclination."

Two distinct bottle-emptying modes were identified. In one mode, the discharge rate is increased due to a high frequency pinch off of air bubbles inside the bottle. In the other mode, it is caused by an increase in volume of the pinched-off bubble at a comparatively lower frequency.

"We've also observed an encapsulated bubble while discharging fluid in a vertically upended bottle," Rohilla said. "Encapsulated bubbles have pinch off sites outside the bottle mouth, contrary to intuition. The presence of a violent ejector jet within inviscid fluids, in which liquid becomes thin due to almost no internal friction, and its complete absence within viscous fluids control the periodicity of the bubbles."

This work proves that bottle geometry and thermophysical properties play a role in reducing the time it takes for a bottle empty.

"We can manipulate the bottle discharge pattern by manipulating bottle geometry," said Das. "An intuitive product-specific bottle design will enable better control of its discharge rate."

The beverage industry and chemical plants are among the applications that will benefit from this better understanding of bottle geometry.

Creating new blood vessels, a process called angiogenesis, for tumors in lymph nodes is different than for tumors in other parts of the body, such as the colon or lung, a team from the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC) reports in the journal Cancer Research. Scientists from the MDC labs of Dr. Armin Rehm, Dr. Uta Höpken and Professor Holger Gerhardt were involved in this project. The team identifies potentially more effective treatment targets to slow tumor growth for lymphoma patients.

Lymphoma is cancer of the lymphatic system, which includes the lymph nodes, spleen and bone marrow. Lymphoma patients with indicators of increased blood vessel development usually have lower chances of survival. They also don't respond well to treatments that have successfully inhibited blood vessel development in other cancer types.

"We hypothesized that tumors in lymph nodes are completely different from solid tumors because the lymph nodes provide such a supportive microenvironment for blood borne tumor cells," said Dr. Uta Höpken, who heads MDC's Microenvironmental Regulation in Autoimmunity and Cancer Lab. Still, it was "absolutely surprising that none of the usual suspects were involved," said Dr. Armin Rehm, who leads MDC's Translational Tumorimmunology Lab.

Eliminating suspects

Blood vessels in early lymphoma are unusually dense and irregular, with a lot more branching than observed in blood vessels of healthy lymph nodes. The pattern of branching has not been observed in solid tumors, in infected lymph nodes or in developing organs, which are typically other sites of neo-angiogenesis.

To uncover the unique signaling pathways that drive this development, the team ran analyses using transgenic mouse models that develop lymphoma, as well as mice implanted with lymphoma cancer cells. They looked at gene expression patterns to see which genes and proteins are most active in the initial phases of tumor development.

Culprits usually implicated in tumor angiogenesis - inflammation, low oxygen levels, and signaling between the base and tip of blood vessels, called Notch signaling - did not show up in the results.

Successful blocks

A group of proteins, called vascular endothelial growth factor (VEGF), are considered primary drivers of normal blood vessel development, as well as angiogenesis in tumors. In most solid mass tumors, VEGF-A is the protein mediating the process, in conjunction with its receptor, called VEGFR-2.

In the early stages of lymphoma, the team discovered VEGF-C is the most active protein. When they tried to block receptor VEGFR-2 to inhibit VEGF-C activity, nothing changed.

But when the researchers blocked a different receptor, VEGFR-3, blood vessel growth was significantly slowed. They also interrupted a receptor for a small protein called lymphotoxin, which is usually needed for normal lymph node development, also helped slow angiogenesis.

The team used two drugs that are already approved for clinical use in autoimmune disorders to inhibit the pathways. They confirmed the treatment also worked on human cells. While not clinicians themselves, the researchers hope the treatment can be taken up for clinical trials to investigate its effectiveness in human patients. "If a few cancer cells survive chemotherapy, it might be possible to prevent relapse by addressing these pathways with immunotherapy," Rehm said.

Watching from the start

A key feature of this study was the timing. The researchers traced angiogenesis in the first twelve days after cancer cells invaded lymph nodes. This gave them a unique opportunity to observe the early "crosstalk" or interaction between tumor cells and the lymph node microenvironment. Only five to ten per cent of lymph node cells were cancerous, and already the lymph node was being restructured. "The changes we saw occur very early and with a very low tumor burden," Höpken said.

Imaging these early changes in high-resolution presented a challenge that required a great deal of diligence. "Lymphoma cells are widely distributed cells within the highly compartmentalized lymph node," said Lutz Menzel, co-first author and post doc in the Translational Tumorimmunology Lab. "Finding lymphoma-induced remodeling of the stroma, when other areas of the lymph node remained unaffected, quite often became a search for a 'needle in the haystack' under the microscope."

The team underscored the importance of animals for this work. Such a study is not possible with human patients, because they are not yet showing symptoms. "Animals provide the advantage to see what is going on at the beginning of disease, rather than the end," Rehm said. "Organoids are simply not far enough developed to mimic the interaction between many different cell types in complex lymph node tissue."

The group plans to continue investigating the relationships between tumor cells and the lymph node microenvironment, and see if single-cell sequencing can reveal even more about the angiogenesis process.

Our brain is steadily engaged in soliloquies. These internal communications are usually also bombarded with external sensory events. Hence, the impact of the two neuronal processes need to be permanently fine-tuned to avoid their imbalance. A team of scientists at the Ruhr-Universität Bochum (RUB) revealed the role of the neurotransmitter Serotonin in this scenario. They discovered that distinct serotonergic receptor types control the gain of both streams of information in a separable manner. Their finding may facilitate new concepts of diagnosis and therapy of neuronal disorders related to malfunction of the serotonin system. The study is published online in the open access journal eLife on 7. April 2020.

Impacting on different streams of information in the brain

„The following everyday life example may sketch the task that the brain needs to solve", explains Dr. Dirk Jancke, Head of the Optical Imaging Group at the Institute of Neural Computation: „Imagine sitting with your family at dinner, a heated debate is going on how to properly organise some internal affairs. Suddenly the phone starts ringing; you are picking up while family discussion goes on. In order to understand the calling party correctly, the crowd in the back must speak lower or the caller needs to speak up. Thus, the loudness of each internal background conversation and external call need to be properly adjusted to ensure non-interfered - that means separable - information transfer." As in this anecdote, comparable brain processes involve serotonin.

Serotonin is a neurotransmitter of the central nervous system, in common parlance called „Happy hormone" because it contributes to changes in brain state and is often associated with effects on mood. The study of the RUB team now demonstrates that serotonin participates also in the scaling of current sensory input and ongoing brain signals.

Controlling neuronal release of serotonin with light

The RUB neuroscientists discovered the underlying mechanisms in experiments that investigated cortical processing of visual information. For their study, they used genetically modified mice in which the release of serotonin could be controlled by light. This mouse line was developed by the group of Professor Stefan Herlitze, Department of General Zoology and Neurobiology, to enable specific activation of serotonergic neurons by an implanted light fiber.

Combining this technique with optical imaging, the RUB team found that increasing levels of serotonin in the visual brain leads to concurrent suppression of ongoing activity and activity evoked by visual stimuli. Two types of receptors played a distinct major role here. "This was surprising to us, because both receptors are not only co-expressed in specific neurons but also widely distributed across different cell types in the brain", says Zohre Azimi, first author of the study. Separable action of these receptors allows distinct modulations of information carrying internal brain communication and evoked sensory signals. Low serotonin levels, as they typically occur during sleep at night, favor internal brain communication, and thus, may promote important functions of dreaming. "Dysfunction in the interplay of these receptors, on the other hand, harbor the risk of an overemphasis of either internally or externally driven information channels", says Jancke. For example, irregular 5-HT receptor distributions caused by genetic predisposition may become manifest in an imbalanced perception of inner and outside world, similar as seen in clinical pictures of depression and autism.

Facilitating understanding of serotonin effects

The scientists hope that their findings contribute to a better understanding of how serotonin affects fundamental brain processes. In turn, their study may trigger future research in developing receptor-specific drugs that benefit patients with serotonin-related psychiatric diseases.

The protein STING (Stimulator of Interferon Genes) is a critical component of the body's innate immune defence system, but can also contribute to chronic autoimmune and autoinflammatory diseases.

Monash Biomedicine Discovery Institute (BDI) researchers led by Dr Dominic De Nardo have discovered the mechanism behind one of two signalling arms involved in the cGAS-STING pathway. Their findings, published in Cell Reports today are important for the field and have significant implications for therapeutic targeting of this pathway.

Beyond being a major component of the host innate immune response to viral infection, the cGAS-STING pathway has also been implicated as a key player in a number of cellular and disease processes, including autoimmune disease (e.g. Aicardi-Goutières syndrome and forms of lupus), autoinflammatory conditions, neurodegenerative disorders and cancer.

It is being exploited in cancer immunotherapies, with research in preclinical models showing that STING activation primes the host's immune system to kill cancer cells.

Once activated, the cGAS-STING pathway has two major outcomes. One is the well-defined type I interferon (IFN) response, which helps combat viruses. The second outcome is a cytokine response, mediated by NF-kappaB, which is important for generating the inflammatory response that counteracts infection and helps the body get back to homeostasis.

"But no-one really knew exactly how these cytokines were being made," Dr De Nardo said.

Dr De Nardo, Group Leader in the Department of Anatomy and Developmental Biology, became curious after reading research papers on the STING interferon response that only briefly mentioned the cytokine response in "throwaway lines".

"As someone who very much likes to understand mechanisms thoroughly, I thought the work in the literature hadn't gone far enough," he said.

"It was an interesting 'unknown'; we thought we should fill in this knowledge gap".

The two signalling arms of the cGAS-STING pathway were thought to be mediated by a single upstream kinase, TANK binding kinase (TBK1). Using a new approach to knockout TBK1 from preclinical models, the researchers demonstrated that TBK1 was essential for the interferon response - consistent with what was known. However, they found that the absence of TBK1 did not affect cytokine production, which was still robust.

They then discovered that a closely related TBK1 homologue, I-kappa-B kinase epsilon (IKK-epsilon), when knocked out, also had no effect on cytokine production. However, knocking out both TBK1 and IKK-epsilon together resulted in the loss of both the interferon and the cytokine response.

"That basically told us that the mechanism that drives the second cytokine pathway depends on both proteins, but that they act redundantly - if one's missing the other one does the job," Dr De Nardo said.

"That was why other researchers hadn't worked this pathway out yet; they didn't delve as deeply as we did," he said.

"We basically described a new model for this pathway, which is exciting."

"What we've done is redefine the pathway that leads to cytokine production downstream of cGAS-STING," Dr De Nardo said.

"It's also significant from the perspective of treating people who might have diseases related to this protein."

The researchers are now examining the mechanisms involved in greater detail.

Dr De Nardo's PhD student, Katherine Balka, is first author on the paper.

"It has been really exciting to unravel some of the details surrounding STING signalling and I look forward to continue to expand on these findings," Ms Balka said.

Professor Benjamin Kile, Executive Dean of the Faculty of Health and Medical Sciences at the University of Adelaide, and Associate Professor Seth Masters from the Walter and Eliza Hall Institute of Medical Research were other senior authors who contributed to the study.

A pair of chemicals used by wallflowers and their kin to ward off predators have evolved to complement each other, with one targeting generalist herbivores and the other targeting specialised herbivores that have become resistant to the generalist defence.

Plants are engaged in an ongoing arms race with the creatures that eat them. They evolve defences to deter plant eaters, while their herbivores evolve counter-defences. The new study, published today in eLife, reveals details of the evolutionary chemical arms race in the wallflower genus Erysimum, a group of flowering plants in the mustard family Brassicaceae.

The first line of defence in all Brassicaceae plants are chemicals called glucosinolates, which are activated when predatory creatures nibble on the plants. More recently, wallflowers have developed a second line of defence by producing chemicals called cardenolides to deter plant-eating creatures that evolved defences to glucosinolates.

"Studying how these two defences evolved in this large genus can help scientists understand the trade-offs that the plants face as they try to defend themselves against multiple enemies," explains lead author Tobias Züst, PhD, Research Associate at the Institute of Plant Sciences, University of Bern, Switzerland.

To do this, Züst and his team sequenced the genome of the wormseed wallflower, a short-lived wild mustard. They next created a detailed family tree for this plant and 47 other wallflower species and compared the diversity and abundance of glucosinolates and cardenolides across these species. They found that the two defences varied independently of each other, and that closely related, geographically co-occurring species shared similar cardenolide traits, but not glucosinolate traits. This is likely a result of separate selective pressures acting on each defence.

"Even though most species co-expressed two different types of potentially costly chemical defences, there was no evidence of a trade-off between glucosinolates and cardenolides," Züst says. "Instead, these two types of chemicals appear to complement each other and do not serve redundant functions."

Züst adds that the emergence of cardenolides corresponds with an explosion in the number of wallflower species, which suggests this second complementary defence may have allowed these plants to succeed and diversify into new habitats.

"Further analysis of the wormseed wallflower genome will be needed to help scientists identify glucosinolate and cardenolide-producing genes in this species, as well as aid our understanding of the function of these chemicals in the evolution of Brassicaceae defences," concludes senior author Georg Jander, Professor at the Boyce Thompson Institute in Ithaca, New York, US.

Key Takeaways:

Researchers identify critical factors at each of three phases of crowdfunding: "friend funding", "getting crowded", and "races to the goal" and the characteristics of crowdfunders contributing to the successful fund raising.

Based on this understanding, fundraisers can maximize both the likelihood of successful fund raising and the amount of capital raised by optimizing fundraising goals, and crowdfunding platforms can optimize their targeting strategies in promotional campaigns and better predict which projects are likely to be successful.

CATONSVILLE, MD, April 6, 2020 - While the concept of crowdfunding is still in its early phases of development, a group of marketing researchers have conducted a study that reveals the most powerful drivers behind effective crowdfunding campaigns. According to the researchers, there are three primary mechanisms that serve as the major drivers of crowdfunding campaigns that yield results.

Crowdfunding is the process of raising capital from a crowd of investors through an online platform in order to produce new products or offer new services. Once a crowdfunding fundraising project reaches its goal, investors begin to receive returns on their investments.

In recent years, crowdfunding has been heralded as an untapped and vast new opportunity for entrepreneurs and start-ups who may have had challenges in obtaining funding from more traditional sources.

It's commonly understood in business fundraising that there are three phases: a "friend-funding" phase, where most funds are contributed by friends and family of the founders; a second phase known as the "getting crowded phase," where the process starts to build momentum beyond friends and family; and the "race to the goal phase," where the process gains momentum until the goal is achieved.

This study looked at this process and identified challenges and opportunities at each crowdfunding phase.

The research study, to be published in the INFORMS journal Marketing Science, is titled "Modeling Dynamics in Crowdfunding." It is authored by Chul Kim of the City University of New York; P.K. Kannan and Michael Trusov of the University of Maryland; and Andrea Ordanini of Bocconi University in Milan, Italy.

"In our research, we suggest three major drivers that lead to the dynamics in crowdfunding process: investors' forward-looking strategic behavior, social interactions among individual investors, and their expectations on the crowd's behavior" said Kim. "We found strong evidence for all three mechanisms and confirmed how they contribute to the dynamic patterns of crowdfunding".

"In the early stage (like the "friend-funding" phase), an individual crowdfunder expects that her investment will encourage other crowdfunders' participation. It can be a strong incentive for her to participate even at the early stage," said Kannan.

"In the middle stage where most of crowdfunding projects are likely to stagnate, it is very important to ignite the crowding process through social interactions among crowdfunders for successful goal completion," said Ordanini. "In the end, once the crowdfunding project gains momentum, investors sitting on the sides waiting for the opportunistic moment will jump in and follow."

"Based on these understandings on the crowdfunding dynamics, we identified for fundraisers the optimal goals that ensure intended results while raising the maximum capital," said Trusov. "For the crowdfunding platforms, we arrived at ways to optimize targeting of the right investors, identifying those crowdfunders who have the potential to contribute the most to the program's success. And, we have found ways to more accurately predict whether a crowdfunding campaign will succeed, and when it will succeed by observing early investment patterns."

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.