Culture

"Probiotic" is a broad term that refers to a range of different microorganisms that confer health benefits. Just as medications are identified by product names that connect them to the conditions they treat, probiotics are referred to by specific names that link them to scientifically-demonstrated health effects. A complete probiotic name includes the Latin name for genus and species, in addition to the strain: for example, Lactobacillus rhamnosus GG.

A global group of scientists, led by Prof. Giovanna Felis of Italy, Prof. Michael Ganzle of Canada, and Prof. Sarah Lebeer of Belgium, has recently published a paper announcing name changes for some of the bacteria that were historically grouped under the category of Lactobacillus. Members of the Lactobacillus genus are among the most popular bacteria found in consumer probiotic products and fermented foods.

The impetus for the name changes comes from new scientific tools developed over the past few decades, which enable scientists to look at bacterial genes. Now that scientists are able to sequence the genes of bacteria, they have information about which ones are closely genetically related and they are changing the bacterial names to better reflect these relationships. Thus, the wide variety of bacteria that were previously grouped under Lactobacillus have been separated into 25 different genera.

According to the naming conventions for all living things, the first species ever described as a Lactobacillus gets to retain its genus name - so the yogurt-making bacterial species Lactobacillus delbruecki will keep its name, along with the bacteria that are closely related to it.

The new paper, which includes International Scientific Association for Probiotics and Prebiotics board member Dr. Sarah Lebeer as co-author, was published in the International Journal of Systematic and Evolutionary Biology. Lebeer says, "This task had been on the agenda of scientists for a while. We are pleased that we managed to unite different international teams working on comparative genomics of Lactobacillus with taxonomy experts, collaborating for the best interest of the whole field."

Lebeer adds, "I admit it's a bit painful to see the names of my favorite bacteria change (including Lacticaseibacillus rhamnosus GG for LGG). Yet I look forward to the new insights provided by this comprehensive analysis of taxonomy, evolutionary history, physiology, and ecology of lactobacilli. The most closely related bacteria sharing most properties now have the same genus name, while lactobacilli that are more distantly related can be more clearly discriminated from each other."

The paper authors have created a website where the previous names and the new names of the bacteria can be searched.

The bacteria in consumer products will remain the same after these name changes are implemented, but their product labels will be updated. Because only the genus names are affected (and many new genus names were deliberately chosen to begin with the letter 'L'), most products will remain easy to recognize.

The paper proposes splitting the existing genus Lactobacillus into Lactobacillus and Paralactobacillus, as well as 23 new genera with the following names: Holzapfelia, Amylolactobacillus, Bombilactobacillus, Companilactobacillus, Lapidilactobacillus, Agrilactobacillus, Schleiferilactobacillus, Loigolactobacilus, Lacticaseibacillus, Latilactobacillus, Dellaglioa, Liquorilactobacillus, Ligilactobacillus, Lactiplantibacillus, Furfurilactobacillus, Paucilactobacillus, Limosilactobacillus, Fructilactobacillus, Acetilactobacillus, Apilactobacillus, Levilactobacillus, Secundilactobacillus, and Lentilactobacillus.

ISAPP has created an infographic explaining these name changes for consumers.

Irvine, Calif., April 15, 2020 - On Tuesday, California Gov. Gavin Newsom suggested that reopening the state's economy will require six steps, the first of which involves "tracing and tracking individuals" in order to identify those who need to remain in isolation.

Researchers at the University of California, Irvine have developed a tool that could be instrumental in this effort. TrackCOVID is a free, open-source smartphone application that permits contact tracing for potential coronavirus infections while preserving privacy.

The team's project is detailed in a paper published recently in JMIR mHealth and uHealth.

"Contact tracing is the process of tracking down and isolating people who may have been exposed to an infectious disease after someone has tested positive," said lead author Tyler Yasaka, a software engineer and junior specialist in otolaryngology at the UCI School of Medicine. "This process has traditionally been slow and inefficient, and current technology-based solutions have privacy concerns because they require continuous tracking of everyone's location."

TrackCOVID works in a different way, he said, by creating an anonymous graph of interactions. Every time a person gathers with others or goes to a public place, he or she can use the app to log contacts by either hosting or joining a checkpoint, which allows possible paths of virus transmission to be discovered. The first person to register as a checkpoint host is given a Quick Response code; others subsequently join the checkpoint by scanning this QR code.

As people congregate with others over time, their interactions are linked to each other anonymously. Anyone who tests positive for COVID-19 can report it through the app without revealing his or her identity. Using the graph of interactions, the app will notify users who may be at elevated risk of exposure.

"We built a simplified simulation model that showed the app is more effective - that it flattens the curve of infections - when more people use it," said co-author Dr. Ronald Sahyouni, a biomedical engineer in UCI's joint M.D./Ph.D. Medical Scientist Training Program and an incoming neurosurgery resident at UC San Diego.

How could this be encouraged? Co-author Brandon Lehrich, who earned a B.S. in biomedical engineering at UCI in 2018, suggested that endorsement by local, state and national government entities would be beneficial - as would enlisting the help of grocery stores and other "essential" gathering places.

The establishments could post signs displaying their QR code, which visitors could scan with their smartphones. TrackCOVID would open automatically in their device browsers, and they'd be anonymously checked into that specific location.

"If the customer happens to be at an elevated risk level, they'll see an alert on their screen," Lehrich said. "If enough public places are doing this, then a lot of contact tracing will happen without any users making a conscious effort other than scanning a QR code when they go shopping. From there, I think people will start to see the value of the app and begin using it to create checkpoints for their private interactions as well."

Yasaka added, "We hope our app goes viral before too many more people come in contact with the more dangerous virus."

Ever since the outbreak of the SARS-CoV-2, scientists have been scrambling to identify the species of origin to understand how the new coronavirus first leapt from its animal hosts to humans, causing the current pandemic infecting more than a million people worldwide.

Scientists have been looking for an intermediate animal host between bats, which are known to harbor many coronaviruses, and the first introduction of SARS-CoV-2 into humans.

Many animals, beginning with snakes and most recently, pangolins, have all been put forth as the likely intermediate, but the viruses isolated from them are too divergent from SARS-CoV-2, suggesting a common ancestor too far back in time---living in the 1960s[1].

Now, University of Ottawa biology professor Xuhua Xia, tracing coronavirus signatures across different species, has proposed that stray dogs---specifically dog intestines--- may have been the origin of the current SARS-CoV-2 pandemic.

"Our observations have allowed the formation of a new hypothesis for the origin and initial transmission of SARS-CoV-2," said Xia. "The ancestor of SARS-CoV-2 and its nearest relative, a bat coronavirus, infected the intestine of canids, most likely resulting in a rapid evolution of the virus in canids and its jump into humans. This suggests the importance of monitoring SARS-like coronaviruses in feral dogs in the fight against SARS-CoV-2."

The findings appear in the advanced access online edition of the journal Molecular Biology and Evolution.

Xia has long-studied the molecular signatures of viruses in different hosts. When viruses invade a host, their genomes often bear the battle scars from fighting off and evading the host's immune system through changes and adaptations found within their genomes.

Humans and mammals have a key antiviral sentinel protein, called ZAP, which can stop a virus in its tracks by preventing its multiplication in the host and degrading its genome. The viral target is a pair of chemical letters, called CpG dinucleotides, within its RNA genome. CpG dinucleotides act as a signpost that a person's immune system uses to seek and destroy a virus. ZAP patrols human lungs, and is made in large amounts in the bone marrow and lymph nodes, where the immune system first primes its attack.

But it's been shown that viruses can punch back. Single-stranded coronaviruses, like SARS-CoV, can avoid ZAP by reducing these CpG signposts, thus rendering ZAP powerless. A similar examination of HIV, another RNA virus, shows that it has also exploited this evolutionary trick to lose CpG in response to human antiviral defenses. One implication of this is that the remaining CpG dinucleotides on the viral genome are likely functionally important for the virus and could serve as target of modification to attenuate virulence in vaccine development.

"Think of a decreased amount of CpG in a viral pathogen as an increased threat to public health, while an increased amount of CpG decreases the threat of such viral pathogens," said Xia. "A virus with an increased amount of CpG would be better targeted by the host immune system, and result in reduced virulence, which would be akin to natural vaccines."

To perform the study, Xia examined all 1252 full-length betacoronavirus genomes deposited into GenBank to date. Xia found that SARS-CoV-2 and its most closely related known relative, a bat coronavirus (BatCoV RaTG13), have the lowest amount of CpG among its close coronavirus relatives.

"The most striking pattern is an isolated but dramatic downward shift in viral genomic CpG in the lineage leading to BatCoV RaTG13 which was reported to be sampled from a bat (Rhinolophus affinis) in Yunnan Province in 2013 but only sequenced by Wuhan Institute of Virology after the outbreak of SARS-CoV-2 infection in late 2019," said Xia. "This bat CoV genome is the closest phylogenetic relative of SARS-CoV-2, sharing 96% sequence similarity."

"In this context, it is unfortunate that BatCoV RaTG13 was not sequenced in 2013, otherwise the downshifting in CpG might have served as a warning due to two highly significant implications," said Xia. "First, the virus likely evolved in a tissue with high ZAP expression which favors viral genomes with a low CpG. Second and more importantly, survival of the virus indicates that it has successfully evaded ZAP-mediated antiviral defense. In other words, the virus has become stealthy and dangerous to humans."

Xia applied his CpG tool to reexamining the camel origin of MERS, and found
those viruses infecting camel digestive system also had lower genomic CpG than those infecting camel respiratory system.

When he examined the data in dogs, he found that only genomes from canine coronaviruses (CCoVs), which had caused a highly contagious intestinal disease worldwide in dogs, have genomic CpG values similar to those observed in SARS-CoV-2 and BatCoV RaTG13. Second, canids, like camels, also have coronaviruses infecting their digestive system with CpG lower than those infecting their respiratory system (canine respiratory coronavirus or CRCoV belonging to BetaCoV).

In addition, the known cellular receptor for SARS-CoV-2 entry into the cell is ACE2 (angiotensin I converting enzyme 2). ACE2 is made in the human digestive system, at the highest levels in the small intestine and duodenum, with relatively low expression in the lung. This suggests that mammalian digestive systems are likely to be a key target infected by coronaviruses.

"This is consistent with the interpretation that the low CpG in SARS-CoV-2 was acquired by the ancestor of SARS-CoV-2 evolving in mammalian digestive systems and interpretation is further corroborated by a recent report that a high proportion of COVID-19 patients also suffer from digestive discomfort," said Xia. "In fact, 48.5% presented with digestive symptoms as their chief complaint."

Humans are the only other host species Xia observed to produce coronavirus genomes with low genomic CpG values. In a comprehensive study of the first 12 COVID-19 patients in the U.S., one patient reported diarrhea as the initial symptom before developing fever and cough, and stool samples from 7 out of 10 patients tested positive for SARS-CoV-2, including 3 patients with diarrhea.

Canids are often observed to lick their anal and genital regions, not only during mating but also in other circumstances. Such behavior would facilitate viral transmission from the digestive system to the respiratory system and the interchange between a gastrointestinal pathogen and a respiratory tract and lung pathogen.

"In this context, it is significant that the bat coronavirus (BatCoV RaTG13), as documented in its genomic sequence in GenBank (MN996532), was isolated from a fecal swab. These observations are consistent with the hypothesis that SARS-CoV-2 has evolved in mammalian intestine or tissues associated with intestine."

Another finding of Xia's study involves viruses recently isolated from pangolins. Nine SARS-CoV-2-like genomes have recently been isolated and sequenced from pangolin and deposited in GISAID database (gisaid.org). "The one with the highest sequence coverage (GISAID ID: EPI_ISL_410721) has an ICpG value of 0.3929, close to the extreme low end of the CpG values observed among available SARS-CoV-2 genomes. Thus, SARS-CoV-2, BatCoV RaTG13 and those from pangolin may either have a common ancestor with a low CpG or have convergently evolved low CpG values."

Based on his results, Xia presents a scenario in which the coronavirus first spread from bats to stray dogs eating bat meat. Next, the presumably strong selection against CpG in the viral RNA genome in canid intestines resulted in rapid evolution of the virus leading to reduced genomic CpG. Finally, the reduced viral genomic CpG allowed the virus to evade human ZAP-mediated immune response and became a severe human pathogen.

"While the specific origins of SARS-CoV-2 are of vital interest in the current world health crisis, this study more broadly suggests that important evidence of viral evolution can be revealed by consideration of the interaction of host defenses with viral genomes, including selective pressure exerted by host tissues on viral genome composition," said Xia.

Researchers from Yale-NUS College in Singapore and University College Cork (UCC) in Ireland have analysed preserved scales from wing cases of two fossil weevils from the Late Pleistocene era (approx. 13,000 years ago) to better understand the origin of light-scattering nanostructures present in present-day insects.

The researchers, led by Yale-NUS Assistant Professor of Science (Life Sciences) Vinod Kumar Saranathan and UCC paleobiologists Drs Luke McDonald and Maria McNamara, found that the wing cases of the fossil weevils contained preserved photonic 'diamonds', one of the many types of crystal like nanoscopic structure that interacts with light to produce some of the brightest and purest colours in nature.

The outer coverings of many insects comprise repeating units arranged in a crystalline formation that interact with visible light to produce structural colours, which typically have a metallic, iridescent appearance. For many of these insects, the iridescent colours perform a variety of functions including camouflage, signalling potential mates, and warning off predators. To date, the evolutionary history of these complex tissue structures has not been clearly defined. This study highlights the great potential of the fossil record as a means to unearth the evolutionary history of structural colours, not only in weevils but also in other insects, and paves the way for further research on the development of these light-scattering nanostructures and the vibrant colours they give rise to.

The researchers used powerful electron microscopes and state-of-the-art synchrotron X-ray scattering and optical modelling techniques to identify and characterise a rare 3D photonic crystal nanostructure in the fossil weevil scales - whose blue and green hues are very similar to those of modern weevils from the same genus - revealing a diamond-like arrangement. Instances of 3D nanostructures are extremely rare in the fossil record. This study marks the second time such nanostructures have been found. The only other instance of such nanostructures found in the fossil record of another weevil was also discovered by Asst Prof Saranathan and Dr McNamara.

The fact that very similar substrate-matching green colours have been maintained over hundreds of thousands of generations suggest that the same selective pressures for camouflage have been acting on these weevils. This is consistent with a recent study by Asst Prof Saranathan and weevil systematist Dr Ainsley Seago that suggests the weevils' colours evolved initially for camouflage amongst their leafy background, before diversifying for other functions such as to signal potential mates or deter predators.

Asst Prof Saranathan, who holds a concurrent appointment at the National University of Singapore's Department of Biological Sciences, said, "It is very interesting to discover that insects first seem to evolve complex 3D nanoscale architectures in order to escape predators by blending in with their background (usually brown or green). Only later do these colours diverge for other uses, such as signalling potential mates or as a warning to predators that the insect is not worth eating."

Researchers using the Gemini North telescope on Hawai'i's Maunakea have detected the most energetic wind from any quasar ever measured. This outflow, which is travelling at nearly 13% of the speed of light, carries enough energy to dramatically impact star formation across an entire galaxy. The extragalactic tempest lay hidden in plain sight for 15 years before being unveiled by innovative computer modeling and new data from the international Gemini Observatory.

The most energetic wind from a quasar has been revealed by a team of astronomers using observations from the international Gemini Observatory, a program of NSF's NOIRLab. This powerful outflow is moving into its host galaxy at almost 13% of the speed of light, and stems from a quasar known as SDSS J135246.37+423923.5 which lies roughly 60 billion light-years from Earth.

"While high-velocity winds have previously been observed in quasars, these have been thin and wispy, carrying only a relatively small amount of mass," explains Sarah Gallagher, an astronomer at Western University (Canada) who led the Gemini observations. "The outflow from this quasar, in comparison, sweeps along a tremendous amount of mass at incredible speeds. This wind is crazy powerful, and we don't know how the quasar can launch something so substantial". [1]

As well as measuring the outflow from SDSS J135246.37+423923.5, the team was also able to infer the mass of the supermassive black hole powering the quasar. This monstrous object is 8.6 billion times as massive as the Sun -about 2000 times the mass of the black hole in the center of our Milky Way and 50% more massive than the well-known black hole in the galaxy Messier 87.

This result is published in the Astrophysical Journal and the quasar studied here now holds the record for the most energetic quasar wind measured to date, with a wind more energetic than those recently reported in a study of 13 quasars [2].

Despite its mass and energetic outflow, the discovery of this powerhouse languished in a quasar survey for 15 years before the combination of Gemini data and the team's innovative computer modeling method allowed it to be studied in detail.

"We were shocked - this isn't a new quasar, but no one knew how amazing it was until the team got the Gemini spectra," explains Karen Leighly, an astronomer at the University of Oklahoma who was one of the scientific leads for this research. "These objects were too hard to study before our team developed our methodology and had the data we needed, and now it looks like they might be the most interesting kind of windy quasars to study."

Quasars - also known as quasi-stellar objects - are a type of extraordinarily luminous astrophysical object residing in the centres of massive galaxies [3]. Consisting of a supermassive black hole surrounded by a glowing disk of gas, quasars can outshine all the stars in their host galaxy and can drive winds powerful enough to influence entire galaxies [4].

"Some quasar-driven winds have enough energy to sweep the material from a galaxy that is needed to form stars and thus quench star formation," explains Hyunseop (Joseph) Choi, a graduate student at the University of Oklahoma and the first author of the scientific paper on this discovery. "We studied a particularly windy quasar, SDSS J135246.37+423923.5, whose outflow is so thick that it's difficult to detect the signature of the quasar itself at visible wavelengths."

Despite the obstruction, the team was able to get a clear view of the quasar using the Gemini Near-Infrared Spectrograph (GNIRS) on Gemini North to observe at infrared wavelengths. Using a combination of high-quality spectra from Gemini and a pioneering computer modeling approach, the astronomers uncovered the nature of the outflow from the object -- which proved, remarkably, to be more energetic than any quasar outflow previously measured.

The team's discovery raises important questions, and also suggests there could be more of these quasars waiting to be found.

We don't know how many more of these extraordinary objects are in our quasar catalogs that we just don't know about yet," concludes Choi "Since automated software generally identifies quasars by strong emission lines or blue color -- two properties our object lacks -- there could be more of these quasars with tremendously powerful outflows hidden away in our surveys."

"This extraordinary discovery was made possible with the resources provided by the international Gemini Observatory; the discovery opens new windows and opportunities to explore the Universe further in the years to come," said Martin Still, an astronomy program director at the National Science Foundation, which funds Gemini Observatory from the U.S. as part of an international collaboration. "The Gemini Observatory continues to advance our knowledge of the Universe by providing the international science community with forefront access to telescope instrumentation and facilities."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

Caution Warranted: Using the Institute for Health Metrics and Evaluation (IHME) Model for Predicting the Course of the COVID-19 Pandemic

The Institute for Health Metrics and Evaluation model for predicting the course of the coronavirus disease 2019 pandemic has attracted considerable attention, including from the U.S. government. According to the authors from the London School of Hygiene & Tropical Medicine, the appearance of certainty of model estimates is seductive when the world is desperate to know what lies ahead, but caution is warranted regarding the validity and usefulness of the mode projections for policymakers. Read the full text: http://annals.org/aim/article/doi/10.7326/M20-1565.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author Nicholas P. Jewel, PhD, can be reached at jewell@berkeley.edu.

URBANA, Ill. ¬- Soybean production in Africa and other developing regions has the potential to alleviate hunger and boost local economies. But the transition from traditional crops such as cowpea or cassava to a major commercial crop such as soybean is fraught with challenges.

The Soybean Innovation Lab (SIL), housed in the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois, is funded by USAID's Feed the Future initiative to help bring research-based innovation and technology to develop soybean production in Sub-Saharan Africa.

"The challenge is to feed the world and strengthen agriculture in developing countries," says Peter Goldsmith, director of SIL and professor of agricultural and consumer economics at U of I.

"We conduct research that provides the answers to real questions facing practitioners working along the value chain, thereby helping to inform smart development and sustainable policies," he adds.

Goldsmith explains that SIL's economics team supplies critical information that can be put into practice by organizations working directly with farmers.

In one study, SIL researchers investigated the viability of soybean production for smallholder farmers in Ghana, especially women. The data originated with a donor organization that wanted to bring soybean production to hundreds of women farmers. The sponsor assumed that using a standard rollout of training and market linkages could make soybean a successful smallholder crop.

Goldsmith and study co-author Courtney Tamimie analyzed soybean adoption and performance data from the project for 453 smallholder farmers in northwestern Ghana from 2013-2015. Their research documented a steep learning curve for adopting soybeans as a commercial crop. This makes soybean a "long-jump" technology that requires significant shifts in production and marketing practices; a greater dependence on production credit; and different forms of commercial risk not found when producing traditional staple crops.

"Smallholder farmers face severe challenges with a broad commercial crop like soybeans; it's very different from a typical smallholder crop such as traditional staples," Goldsmith says.

"Bringing in a crop that is management heavy and requires new technology is very difficult for farmers who are not part of a system."

For a transition to soybean to be economically feasible, the authors say, smallholder farmers need to be part of a larger system that can provide guidance and support, because the technical load of soybean production is high.

"There are many successful outgrower models whereby the system provides the technology, services, credit, and extension support throughout the crop year, in exchange for grain at harvest," Goldsmith says.

Systems such as cooperatives, outgrower networks, or commercial input/seed companies give farmers access to knowledge that boosts yields and income. Through the system, the farmer receives bundles that include all the components for high soybean yields and a profitable crop, such as certified seed, key inputs, and management support. Much like U.S. farmers, who operate within a rich support network of technology suppliers and advisors, smallholders in Africa also need to be part of a commercial crop system in order to stay competitive.

"In developing countries, the typical model is the independent, smallholder farmer. But that is not viable for a technology- and management-heavy commercial crop like soybean," Goldsmith says. "That's the nature of soybean in a developing country, and this was not known before SIL's research."

A second recent study from the economics team at SIL addressed whether soybean prices are abnormally low, thus making profitable soybean production difficult. Edward Martey, economist at the Savanna Agricultural Institute in northern Ghana, led a team to analyze soybean prices across six marketing regions in Ghana. The researchers note that common thinking among practitioners and their farmers was that low prices, not low yields, were to blame for poor profitability from soybean production in Ghana. Martey and co-authors Goldsmith and Nicolas Gatti show that this is not the case.

Soybean prices in Ghana compare quite favorably to international prices and are consistent with supply and demand factors in the country. The researchers did note that there is significant seasonality due to insufficient storage, poor road infrastructure, and challenging logistics during the harvest period.

"The price is very low at harvest and very high the week before harvest, because the country has very little storage capacity," Goldsmith explains. However, prices overall were comparable to world prices, and sometimes they were even higher.

The researchers conclude that it's not low prices that prevent adoption and profitability of soybean among smallholder famers in Ghana.

"The prices are fair; it's that yields are too low, averaging about 10 bushels per acre for the average farmer, who applies few inputs and uses saved seed," Goldsmith says. "So the question becomes, how can we help farmers increase yield?"

The SIL economics team also released a third study, looking at soybean grain and seed quality, in the series on soybean economics in Ghana.

"The price is not just a function of the world price or supply and demand. It's also a function of the quality of the grain," Goldsmith notes.

In the developed world, pricing based on grain quality is well understood and transparent.

"In the U.S., when you take your grain to the elevator, there's a posted price and then there's a discount schedule for a set of attributes, including foreign matter, moisture, cracks and breaks," Goldsmith explains.

However, developing countries do not have a reliable system of evaluating discounts, which can vary from buyer to buyer, and across the crop year. Poor information on quality hurts farmers who may be overly penalized, but also may not receive proper information to encourage delivery of quality grain and seed.

To better understand the relationship between grain quality and prices, Martey and Goldsmith conducted an experiment to understand the buying process of 227 traders in Ghana. That included three classes of traders: those who buy from farmers and sell in the local marketplace; those who buy grain and then sell it to the processors in the central part of the country; and those who are agents buying for processors.

The study examined trader preferences and reasons for price discounts. Results indicated traders discount for attributes such as off color, small grain size, low oil levels, and high contamination with foreign materials.

While differences across trader types exist, discounts are consistent with hypothesized behavior and are not overly aggressive. Poor and variable grain and seed quality hurt farmers as they seek clear signals about market needs, as well as processors who struggle to operate efficiently. Greater transparency and the adoption and enforcement of national grades and standards would go a long way in supporting the development of the soybean industry in Ghana, the researchers say.

"These and other studies from SIL provide research-based information about the challenges facing soybean development in Africa by supplying practitioners and their organizations with critical knowledge that can better inform their policies and practices," Goldsmith says.

URBANA, Ill. - Public parks can be valuable assets for communities, but crime in the area can "lock up" that amenity value. Crime directly affects the use that people get from their local parks. If crime is reduced, the environmental value can be unlocked, a new University of Illinois study shows.

"Our research is the first to rigorously quantify this effect, which turns out to account for nearly half of the total value of parks in major U.S. cities," says Peter Christensen, environmental economist at U of I, and one of the study's authors.

The importance of safety in parks is intuitive; yet it had not been well-understood. In fact, other studies have failed to account for the complementarity between safety and parks, and have concluded that public parks provide little value to a community.

Christensen explains that "several studies estimate amenity value using city-wide samples that include both safe and dangerous parks. This is like taking the average of an amenity and a dis-amenity. It can produce noisy estimates and the appearance of zero value, which may not actually reflect the value of any park in the sample."

And there are other implications. "These kinds of results can fuel the misconception that people in some inner-city neighborhoods, often minority communities, do not value their parks. Our study shows that in fact they do. And that value goes up as neighborhood parks are made safe," Christensen says.

It's challenging to directly estimate the value of public goods such as parks. Economists have developed methods that make use of economic behavior in the housing market, which captures the value of environmental amenities that households will pay to live near. The housing market also captures the losses from disamenities such as landfills or, in this case, crime.

Christensen and co-authors David Albouy and Ignacio Sarmiento-Barbieri analyzed housing prices from Chicago, Philadelphia, and New York over a 15-year period. The data were provided through a unique data sharing agreement with Zillow, the online real estate company. Christensen, who helped develop the agreement, says it provides scholars with free access to rich data sets that would otherwise cost millions of dollars in institutional subscriptions.

"This allows economists and others to gain traction on research and policy questions that have been around for a while but have been difficult to tackle without modern empirical methods," he says.

The paper, published in Journal of Public Economics, combines the prices and characteristics of all properties transacted in each of the three cities with location-specific crime reports that identify the exact address or geo-location of each incident. Through statistical analysis with heavy data and computational requirements, the researchers were able to rule out other factors and isolate the relationship between property values and changes in crime rates within a half mile of the more than 1,300 public parks in the sample.

The study found that housing value increases by 5% within a half mile of a park, if the area is safe. As you get further away from the park, the effect diminishes and ultimately disappears.

If crime levels are double the average rate, there is no premium value in housing prices near parks. And if crime rates are higher than that, there is a negative effect of up to 3%.

In other words, parks may make crime (already a "public bad") worse, Christensen says. "A park can actually become a disamenity in the sense that you would pay to the live away from it."

In many of the study locations, crime has been reduced over the 15-year period, while in other areas it has remained constant or increased. The study shows that where crime has gone down, the inherent housing value of parks has been unlocked. And this unlocked value is much larger than you might expect, the researchers note. They estimate that reductions in crime have "unlocked" almost $7 billion in property value near urban parks in the Chicago, Philadelphia and New York and calculate another $10 billion of potential value that is still locked up.

Christensen says these findings have implications for public policy. "The first implication is that policymakers need to consider the considerable potential to unlock amenity value through increased safety. The other side of this coin is that terrific parks will lose value if a neighborhood becomes unsafe. This has happened over the past several decades in a number of neighborhoods in the sample," he notes.

A second implication is that allocating resources to reduce crime near parks through targeted efforts such as hotspot policing might be an important first use of public funds. The value of enhancing park features, such as building a new playground in a dangerous park, may be limited by the crime risk.

Christensen cites the recent spike in homicide risk in Chicago. "A number of those shootings that are in our data have involved children caught in the cross-fire in neighborhood parks. These are tragedies for families and communities that can also affect a neighborhood's use of public space in the aftermath," he says.

"It is well-documented that open space is in short supply in many urban areas. For communities that are already housing-constrained and may not be able to commit additional land resources to open space, policymakers and parks departments can consider ways of unlocking value through complementarities like public safety," he says.

"Complements like this [between safety and parks] are attractive because they can provide larger returns to public investments. Tax dollars that reduce crime near parks produce benefits from the overall reduction of risk and also because the park is now a much more valuable place."

Christensen notes that the study does not address the broader implications of how increased property values may affect long-term changes in the composition of the neighborhood. "We do not directly address the issue of gentrification in the current paper," he says. "But policies that are aimed at addressing this complementarity between safety and parks need to consider the longer-run dynamics that can result from unlocked amenity value."

A University of Cincinnati ear, nose and throat specialist says your nose may hold a clue in identifying COVID-19.

The loss of smell may be a key indicator.

Physicians are increasingly recognizing the importance of the nasal cavity in determining the physiology of COVID-19, explains Ahmad Sedaghat, an associate professor in the University of Cincinnati College of Medicine's Department of Otolaryngology-Head and Neck Surgery and an UC Health physician specializing in diseases of the nose and sinuses.

"COVID-19 is not associated with the symptoms that are typically associated with a viral cold such as nasal blockage or mucus production," says Sedaghat. "This distinction is also why it is fairly easy to distinguish COVID-19 from seasonal allergies.

"COVID-19 is associated with a fairly unique combination of nasal symptoms: a sudden loss of one's sense of smell, also known as 'anosmia,' without nasal obstruction," said Sedaghat. "The occurrence of sudden onset anosmia without nasal obstruction is highly predictive of COVID-19 and should trigger the individual to immediately self-quarantine with presumptive COVID-19."

Most individuals experiencing COVID-19 report symptoms two to 14 days after exposure such as fever, cough and shortness of breath. Medical assistance is needed if individuals have trouble breathing, persistent pressure or pain in the chest or confusion or inability to rouse, according to the Centers for Disease Control and Prevention. For most, recovery comes without assistance.

Sedaghat's conclusions are available online in the scholarly journal Laryngoscope Investigative Otolaryngology, where he explains that anosmia without nasal obstruction is "a highly specific indicator of COVID-19."

His findings are based on his review of 19 studies which describe the sinus and nasal disorders reported in relation to the current coronavirus plaguing the nation. Sedaghat's published paper also references a recent study led by Paris physicians Dominique Salmon and Alain Corré, which shows that out of a group of 55 patients presenting with anosmia without nasal obstruction 94% were found to test positive for COVID-19 by nasal swabbing and polymerase chain reaction tests.

Sedaghat said COVID-19 can be spread when the virus, if present in the body, is produced in the lining of the nose and then released into mucus. "When someone sneezes, this mucus -- which contains the virus -- is aerosolized outwards. Similarly, if someone wipes their nose and then touches surfaces without washing their hands first, that could lead to spread of COVID-19," explains Sedaghat.

Loss of smell can occur during anytime an individual is infected with COVID-19, but when this occurs as an initial symptom it is particularly instructive, says Sedaghat.

"A sudden loss of one's sense of smell wouldn't trigger most people to think they have COVID-19," explains Sedaghat. "These individuals could continue business as usual and spread the disease as a carrier. The guidelines for when to formally test for COVID-19 remain fluid in the setting of limited tests. But if someone experiences anosmia without nasal obstruction, aside from quarantining, it would not be unreasonable to reach out to one's primary care physician about getting tested."

Sedaghat says the nasal cavity is likely the major site of entry and infection by COVID-19 since at least 90% of inhaled air enters the body through the nose. "Nasal virus production is at very high levels and tends to occur early in the disease process while patients are still asymptomatic or having very mild symptoms," he says.

KANSAS CITY, MO -- Researchers at the Stowers Institute for Medical Research have fine-tuned a method to pinpoint surfaces within large multi-protein complexes that are close to, and likely to be directly interacting with, one another.

In a paper published online April 14, 2020, in Cell Reports, members of the Washburn Lab describe the combination of three approaches -- affinity tag protein purification, chemical crosslinking with high-resolution mass spectrometry, and computational molecular modeling with protein docking -- to capture information about neighboring surfaces within the Sin3/HDAC protein complex.

"Putting all these pieces together gives us a new perspective on how protein complexes are put together," with the potential to provide more information more quickly, explains Michael Washburn, PhD, director of the Stowers Proteomics Center.

"The capabilities have all existed, and have been used together a bit, but not in great numbers yet," Washburn says. "It's certainly complementary to existing techniques such as nuclear magnetic resonance (NMR), cryo-electron microscopy (EM), and X-ray crystallography, to really understand how protein complexes assemble, and to see -- how are they really interacting? What happens when you perturb them with drugs or mutations?"

The Sin3/HDAC complex functions in chromatin remodeling and human cancer biology by bringing histone deacetylases (HDACs) to specific locations in the genome and removing acetyl groups from histone tails, thereby suppressing gene transcription. Although the components of the Sin3/HDAC complex have been well defined, high-resolution descriptions of the large multi-protein complex have been difficult to achieve using any one technology.

The problem with mass spectrometry alone, says Charles Banks, PhD, a research specialist in the Washburn Lab, and co-first author of the paper, "is that we can only identify the proteins in the tube. We don't know anything about which proteins are physically interacting with which other proteins."

While assays for individual protein interactions can be done, they are often time-intensive, Banks explains. "What would be really good is if we could capture some sort of structural information about the intact complex before we separate the proteins, and that's where crosslinking comes in."

The crosslinker used in this study, disuccinimidyl sulfoxide (DSSO), can crosslink amino acids - specifically lysine residues - in protein complexes that are within about 30 angstroms of one another. And, says Washburn, it "does something inside the new mass spectrometers that is very clever" - it can be cleaved, essentially providing fingerprints of crosslinked peptides.

"If I see a crosslink between two lysine residues, that means in the fully intact folded protein, those lysines are quite close together, giving us positional information," explains Banks. "And if I've got two different proteins, and two lysine residues - one from each protein - crosslinked together, that means those lysines in those two proteins are usually very close together, which is consistent with the proteins interacting with each other."

Then, says Banks, they are able to use inter-protein crosslink information to try to dock existing crystal structures together, similar to assembling pieces of a 3D puzzle.

In this study, led by Banks and co-first author Ying Zhang, PhD, a scientist in the Proteomics Center, the Stowers researchers isolated Sin3/HDAC complexes from HEK293T cells, using HaloTag affinity purification and the SAP30L subunit as bait. After chemical crosslinking, they found 66 inter-protein crosslinks, and 63 self-crosslinks for 13 Sin3 subunits, of which they were able to use molecular modeling to determine the relative positions of 5 subunits (SAP30L, HDAC1, SUDS3, HDAC2, and ING1) around the Sin3A scaffold.

"We think of Sin3A as a platform on which all the other subunits assemble," explains Banks. "We still aren't sure which subunits can bind to Sin3A at the same time, although we know that some of them certainly don't bind at the same time."

"But why are there all these other subunits other than the HDACs? Why can't you just recruit the HDACs?" he asks. "We think that probably, the Sin3 complexes control transcription of a specific set of genes, maybe at a specific time and place in specific cells, and we think the other subunits are probably governing that specificity."

When asked about future research directions, Banks replies, "we're a bit limited with our crosslinker at the moment, because it will only capture information based on two lysines being close to each other. It would be really nice to have different crosslinkers that could crosslink between other amino acids, especially if I have another favorite protein that I'd like to study, that does not have many lysines in its sequence."

Molecular modeling with crosslinking information is "like laying the foundation for getting the complete structure of really large complexes, which is hard to do," says Washburn.

"In the future, we can imagine taking what we've done so far and trying to do cryo-EM on those components, and seeing how the two datasets complement each other. Cryo-EM is an amazing technology, and coupling that with crosslinking mass spectrometry can give a much clearer picture of what these molecules look like at the actual interfaces," explains Washburn.

"This is a convergence of technologies that allows us to, going forward, do this on really any protein complex under almost any circumstance"-- even, yes -- toward understanding how coronavirus proteins interact with human protein complexes.

"You just have to be able to purify it. If you can get enough material, you can really study any protein complex. It's a matter of doing good biochemistry and preparing a good sample. If you can get really spectacular data, you can build models like this," Washburn continues.

"I haven't been this excited about new capabilities in a long time," he says.

Other coauthors of this work include Sayem Miah, PhD, Yan Hao, Mark K. Adams, PhD, Zhihui Wen, Janet L. Thornton, and Laurence Florens, PhD.

This work was funded by the Stowers Institute for Medical Research and by the National Institute of General Medical Sciences of the National Institutes of Health (award RO1GM112639 to MPW and award F32GM122215 to MKA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Lay Summary of Findings

Sin3/HDAC is a large multi-protein complex that is normally responsible for "turning off" a specific set of genes. When its main scaffold is mutated, the complex is also implicated in cancer biology, and is targeted for treatment of many human cancers, including triple negative breast cancer and pancreatic cancer. Although Sin3/HDAC has been well studied and its component subunits have been identified, getting a clear picture of how the subunits assemble has been difficult.

Michael Washburn, PhD, of the Stowers Institute for Medical Research, and his lab have long used proteomics and protein mass spectrometry to study complexes in protein networks. Over the last few years, several technologies have improved, and when combined, allow researchers to obtain unambiguous information regarding the spatial arrangement of neighboring surfaces within multi-protein complexes.

A report from the Washburn Lab, published online April 14, 2020, in Cell Reports, describes the use of three existing approaches -- affinity tag protein purification, chemical crosslinking with high resolution mass spectrometry, and computational molecular modeling with protein docking -- to pinpoint specific surfaces, within the intact protein complex, that are in very close proximity with each other. In total, they identified 66 inter-protein crosslinks (between two different proteins) and 63 self-crosslinks (within the same protein) for 13 Sin3/HDAC subunits, some of which were mutually exclusive.

The combination of these approaches has been used occasionally in the past, but moving forward, the combined technologies will likely be used much more, allowing researchers to pinpoint interacting surfaces in virtually any protein complex, obtained from any source. These capabilities can be further combined with other powerful techniques such as cryo-electron microscopy to provide an even higher resolution picture of the interactions at interfacing surfaces within intact protein complexes.

Until now, the immune sensor TLR8 has remained in the shadows of science. A research team led by the University of Bonn has now discovered how this sensor plays an important role in defending human cells against intruders. The enzymes RNaseT2 and RNase2 cut ribonucleic acids (RNAs) of bacteria into small fragments that are as characteristic as a thumbprint. Only then can TLR8 recognize the dangerous pathogens and initiate countermeasures. The results have now been published in the renowned journal "Immunity".

When bacteria or the pathogens that cause malaria invade living human cells, these cells can be very unwelcoming. They try to drive away the by releasing reactive oxygen species - a principle that is also used in toilet cleaners and disinfectants. The cell enters a state of emergency, places itself in a kind of quarantine and produces inflammatory messengers that attract and activate other immune cells. These immune cells can then kill infected cells or form antibodies against the pathogens and thus, ideally, fight off the infection in the long term.

But how does the living human cell recognize if an undesirable guest is even there? Like a radar system, the immune sensor with the scientific name Toll-like Receptor 8 or "TLR8" monitors whether tell-tale ribonucleic acids (RNA) appear during the recycling of dead cells or ingestion of live pathogens, indicating foreign invaders. This is because, as in a digestive process, complete cells and cell components that are no longer needed are taken up and broken down into their individual components and reassembled into new cell structures. If bacteria or other pathogens are hiding in these components, their different RNAs will appear on the radar screen of TLR8 during the recycling process.

TLR8 stayed in the shadows

"The immune sensor TLR8 was neglected for a long time," says Dr. Eva Bartok. "The reason is that it is not active in mice, but many immunological studies are carried out on these model organisms." In humans it plays an important role. As the research group leader at the Institute for Clinical Chemistry and Clinical Pharmacology at the University Hospital Bonn explains, it was only the advent of the CRISPR-Cas9 gene editing that made it possible to understand the importance of the TLR8 immune sensor in human cells.

The researchers around Dr. Eva Bartok and Prof. Dr. Gunther Hartmann from the Cluster of Excellence ImmunoSensation at the University of Bonn first deactivated TLR8 by removing the gene using CRISPR-Cas9. "The consequence was that human cells were no longer able to recognize RNA from bacteria," says Thomas Ostendorf, lead author from Bartok's research group. "This demonstrates the central importance of TLR8."

CRISPR-Cas9 gene editing enabled the novel study

By switching off other genes, the researchers discovered two important tools of the immune system: RNaseT2 and RNase2. Both enzymes ensure that the immune sensor TLR8 is able to detect the tell-tale ribonucleic acids of bacteria and malaria in the first place. "You can perhaps picture long RNA as balls of wool, the loose end is not really visible," explains Thomas Zillinger, another lead author of the work from Prof. Hartmann's group. As long as the RNA are present as tangled balls, their sequence cannot be identified. TLR8 can only detect whether RNA comes from the host or an intruder once it has been broken down into readable fragments by RNaseT2 and RNase2.

The scientists initially worked with cell culture lines from tumors. To validate the results, they used blood cells from patients with a very rare congenital inflammatory disease in which RNaseT2 cannot be produced due to a genetic defect, and who suffer from severe mental and physical disability as a result. "The primary immune cells from these patients enabled the Bonn researchers to validate the results from the CRISPR-Cas9 model cell lines very well," says Prof. Dr. Jutta Gärtner, Director of the Department of Pediatrics and Adolescent Medicine at the University Medical Center Göttingen, who first described this disease and provided the Bonn researchers with immune cells from these rare patients.

Basic research for vaccines and immunotherapies

"The interaction of RNaseT2 and RNase2 with the immune sensor TLR8 is a key element of the immune response against pathogens inside cells," says Bartok. This finding could potentially lead to the development of new vaccines against infections or immunotherapies for cancer by activating TLR8 more strongly and specifically via tailor-made RNA molecules, thereby turbocharging the immune system. "However, this will require further intensive translational research and development. It may possibly lead to the spin-off of a new biotech company, so that the considerable resources required for clinical development can be made available," adds Prof. Hartmann.

In recent decades, alternative food supply movements have arisen. These are based on greater society involvement in coordinating and making decisions regarding food. These short food supply chains translate into producer markets, food co-ops and consumer groups in which a group of people organizes with producers in order to get supplies of necessary products.

Despite the fact that these systems usually have common elements running through them, such as the search for food sovereignty, nearby producers and local products and the assessment of good agricultural practices, the territorial factor molds the specific characteristics of each chain depending on the city or town where it is located.

Along these lines, a study led by University of Cordoba researcher Liliana Reina Usuga, in which College of Agricultural and Forestry Engineering Professor Tomás de Haro and Granada's Institute of Agricultural and Fisheries Research and Training researcher Carlos Parra-López also participated, analyzed the governance processes, as in the coordination mechanisms of the stakeholders within the territorial short food supply chains in Córdoba and Bogotá, two cities that have the same chains, but function differently due to each city's characteristics. Different population densities and distances in each city determine the way the collectives who participate in these supply chains are organized.

In search of governance processes, they first identified social narratives, the theory upon which these initiatives are created. By means of the Q method, which is a methodology that arose in psychology and is used to identify social narratives, they worked with different stakeholders: producers, NGOs, universities and public administration. Food activism, development aid, the view of these chains as a market niche, local self-management and social and environmental awareness were the five narratives shared by the players in these markets on both sides of the Atlantic, though some narratives were stronger than others depending on the city. While in Córdoba the food activism narrative was stronger, meaning that those who are in these kinds of movements are people who are committed to the environment and social justice, and are driven by this undertaking, in Bogotá there was a greater slant toward development aid, due to many of the chains there being fostered by NGOs and aid workers.

Once these narratives were identified, coordination mechanims were analyzed, such as decision-making (at an assembly or by consensus), setting prices of food and conflict resolution among the groups. According to these mechanisms, a network governance is set up, in which different stakeholders participate horizontally with low central power. In addition, reflexive governance is established, as these movements create spaces for dialog and collective action in order to question food conditions and to suggest alternatives.

With the fostering of reflexive governance and network governance in which society and chain stakeholders are involved, we are coming closer to more sustainable and democratic food systems, passing from the concept of food security (access to and availability of food) to that of food democracy (active participation in decisions on what kinds of food to produce and how to do so).

The public playing a stronger role in deciding about their nutrition and using local chains decreases people's vulnerability when facing food system crises.

A drug that is well-tolerated in patients and prevents cancer coming back in mice has been identified by researchers at the Francis Crick Institute.

One of the biggest challenges in cancer research is preventing cancer returning in patients who have already had treatment. A reason for these relapses is that some cancer cells survive and are able to grow into a new tumour.

As part of the study published in Nature Communications, researchers showed that an experimental drug, Quisinostat, could stop tumour re-growth after initial treatment in live mice, and prevent expansion of surviving human cancer cells in culture.

The drug works by increasing the amount of a protein called histone H1.0 within the tumour cells. This protein stops the cancer cells from replicating and so the tumour from growing.

When the team tested the drug on tumours in mice, it halted tumour growth. And, when it was tested on cells taken from patients with breast, lung or pancreatic cancer, the cancerous cells were trapped in a non-dividing state.

The researchers hope that if proven to be effective in further tests and clinical trials, this drug could be given to patients after treatment to prevent any cancerous cells left behind from driving disease relapse. Importantly, the effect of Quisinostat does not depend on how cancer cells survived treatment, something that varies from patient to patient, and across cancer types, and could have a potentially broad therapeutic benefit.

Cristina Morales Torres, lead author and Principal Laboratory Research Scientist in the Cancer Epigenetics Laboratory at the Crick, says: "This drug works by disabling the cells that fuel long-term cancer growth and drive disease relapse. These early findings even suggest it may be more effective than commonly used drugs that inhibit tumour growth.

"Further research is still needed to confirm whether this drug could prevent cancer coming back in people or if it could be used to control someone's disease long term."

Importantly, this early work also suggests that Quisionostat could impact cancerous cells while leaving healthy cells unharmed.

Paola Scaffidi, co-author and Group Leader of the Cancer Epigenetics Laboratory at the Crick and Professorial Research Associate at the UCL Cancer Institute, says: "Just like stem cells that continuously produce progeny to keep our normal tissues healthy, cancer cells grow, divide and use energy. That's why finding a potential drug that halts tumour growth without hurting normal cells has been a challenge. Excitingly, with Quisinostat, we've seen no harm to healthy stem cells in our initial studies."

The next step for these researchers will be to understand why Quisinostat has a different effect on healthy and malignant cells and whether histone H1.0 can tell us what makes a cancer cell distinct from a stem cell.

Researchers have been able to identify and track the exchange of genes among bacteria that allow them to become resistant to drugs, according to a new study published today in eLife.

The findings add to our understanding of how this exchange of genetic material, also known as horizontal gene transfer, happens in bacteria that cause infections in hospitals. They also highlight that while this transfer is likely to happen frequently, it is a complex process and challenging to study with current methods.

The horizontal gene transfer of mobile genetic elements allows otherwise harmless bacteria to hand off genes that provide resistance to antibiotics, turning them into drug-resistant 'superbugs'. This has led to significant problems in hospitals especially, where bacteria have harnessed the power of horizontal gene transfer to become resistant to both antibiotics and disinfectants, allowing them to cause severe infections in patients.

"The question of how to stop bacteria from exchanging drug resistance genes has challenged infectious disease researchers for decades," says first author Daniel Evans, Research Specialist in the Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, US. "To tackle this challenge, we need to know where and how these genes are being shared in hospitals."

To investigate this, Evans and his team screened the genomes of more than 2,000 clinical bacterial isolates gathered from a single hospital over 18 months. The isolates were collected through the Enhanced Detection System for Hospital-Acquired Transmission project at the University of Pittsburgh.

Once the team had identified possible mobile genetic elements in the bacteria, they searched through the patient care data associated with the bacteria that had elements of interest to see whether horizontal transfer might have happened at the hospital.

Their results determined that many of the mobile elements found in the study were likely being shared among hospital bacteria. In one case, the team identified a plasmid - a circular piece of DNA found in bacterial cells - that encoded multidrug resistance and appeared to have been horizontally transferred between bacteria infecting two separate patients.

"Our work shows how bacterial whole-genome sequence data, which is increasingly being generated in clinical settings, gives us the opportunity to study horizontal gene transfer between drug-resistant bacteria in hospitals," concludes senior author Daria Van Tyne, Assistant Professor of Medicine in the Division of Infectious Diseases, University of Pittsburgh School of Medicine. "We hope these findings, along with future studies, will be useful for designing new strategies to prevent and control multidrug-resistant bacterial infections in patients."

The discovery that immune T cells have a spectrum of responsiveness could shed light on how our immune system responds to infections and cancer, and what goes wrong in immune diseases. Researchers at the Wellcome Sanger Institute, Open Targets, Biogen, GSK and their collaborators found that T cells responded very differently to immune signals the more 'training' they had been exposed to, rather than being a simple switch from naïve to experienced. This could help guide research into finding drug targets for immune diseases such as asthma and rheumatoid arthritis.

Today's study (14th April), published in Nature Communications, also revealed that even highly trained memory T cells are less rigidly specialised than previously thought, and are able to respond to new immune signals. This has implications for immune research, and could help understand for example how the body responds to infections.

T cells are key white blood cells that fight infection and disease, and act like police directing the immune system response. Babies are born with inexperienced - naïve - T cells, which change as they come into contact with bacteria or viruses, to create specific memory T cells that can 'remember' fighting against these infections. These memory T cells can then react more quickly the next time they meet the same threat, telling the immune system to remove the infection rapidly. This is how vaccination protects against disease, by delivering a safe form of an invading virus or bacterium, to train our immune system by building up specific memory T cells.

Problems with T cells can result in severe immune deficiencies, leaving people susceptible to infections. Alternatively, in autoimmune diseases such as rheumatoid arthritis and type 1 diabetes, the body can mistake some of its own cells as a threat and switch on an inappropriate immune response, leading to the body attacking itself.

To better understand how memory T cells form and respond during disease, researchers took blood from healthy volunteers and analysed their T cells. They identified exactly which genes were switched on in each individual T cell, indicating what the cell was doing. They also tested these T cells with different immune molecules, called cytokines, to mimic how they might behave in the body.

The researchers discovered that instead of having a simple switch, from naïve to memory cell, there appeared to be a whole continuum of T cell development. They revealed that the more often a T cell had been activated by one signal, the further along the line of memory T cell development - its 'training' - it was, and the faster it could respond to that specific signal.

Eddie Cano Gamez, a first author on the paper from the Wellcome Sanger Institute and Open Targets, said: "Previously people thought that memory T cells had two stages of development, but we discovered there is a whole spectrum of memory experience. From naïve T cells that have never been activated, to highly trained memory T cells which can react quickly, and many intermediate T cells in between. This spectrum not only affects how fast a cell can respond, but even what signals it can respond to."

The study showed the T cells also had a continuum of responsiveness to other chemical signals, revealing they were less specialised than previously thought. They found that even highly trained memory T cells could be triggered by other, new immune signals.

The researchers discovered that some signals created very different responses in memory cells, depending on their experience level. When a specific chemical signal (transforming growth factor -TGF) was added to naïve T cells, they responded by producing regulatory T cells to calm down the immune system. However, the same chemical had the opposite effect on experienced memory cells, triggering them to release more chemicals that cause inflammation.

The collaboration between researchers at the Sanger Institute, GSK, Biogen and other Open Targets partners, will bolster the translation of these research results into new treatments.

Dr Gosia Trynka, senior author from the Wellcome Sanger Institute and Open Targets, said: "We were surprised to see how flexible and complex the memory T cells' response could be. Understanding this varied T cell response could help us understand our response to infections such as viruses, and also give clues to what is going wrong in immune diseases such as asthma and type 1 diabetes. By understanding the pathways involved in normal immune response, we aim to find better drug targets for developing new medicines."