Culture

Despite having been formalized as a species in 1936, Wolbachia pipientis remains an elusive microbe. The reason why relates to the relationship it establishes with its hosts. Wolbachia lives inside the cells of 40% of the arthropods, in their majority insects, intertwined in a symbiosis so complex that it can no longer survive on its own. "Guessing what it takes to grow and manipulate it outside the host might not be possible", says Luís Teixeira, IGC principal investigator. And, so far, despite countless attempts, no one has succeeded in culturing this bacterium or modifying its genetic sequence.

Before joining the team led by Luís Teixeira, Elves Duarte was interested in studying the symbiosis between Wolbachia and mosquitoes. After meeting Luís, he became fascinated by the availability of genetic tools in the fruit fly and the two ended up mixing ideas to study the genetic basis of Wolbachia growth regulation. "We wanted to do something new and try to manipulate the genetics of Wolbachia. This was the challenge", Luís Teixeira explains. The team focused on a star host species--Drosophila melanogaster, commonly named fruit fly, a long-time runner the field of genetics that is small and easy to maintain, even in large numbers. They screened more than a thousand flies in a variety of conditions to find new over-proliferative mutants of Wolbachia. "This would not have been achieved so easily in other organisms: working with a model organism such as the fruit fly was essential", Elves says.

Wolbachia depends on the reproduction of the host to transmit itself from mother to progeny. How much it grows dictates its cost for the host and the chances of being eliminated. "We wanted to understand the relation between growth and the cost or benefit Wolbachia implies for fruit flies", Luís details. The benefit was analyzed by looking at the antiviral protection conferred by this bacterium and the cost evaluated by looking at longevity of the flies. The team found that protection for the fly depends on the amount of Wolbachia at the moment of infection, whereas the cost relates to how fast it grows in the adult host. "This allows us to dissociate these two variables: the benefit and the cost. And from here we can think of new ways to obtain a Wolbachia that confers protection, but is not too costly", Luís reveals.

The viruses that cause dengue, zika or yellow fever are spreading in the world. Mosquitoes carrying them are increasingly found in places where they did not exist before. Several ongoing studies are already using Wolbachia in mosquitoes to control the spread of dengue virus, for example. "There are already people that were not infected because of this technology", Luís says. "But, in the long run, we are not sure how effective it will be and if the protection it gives is enough. So, it is important to think how we can improve this strategy and fully understand what are the factors that influence it", Luis remarks. Studying the genetic basis of Wolbachia proliferation is an entry door to grasping the fundamental biology that underpins the way it interacts with its hosts and how its growth is regulated.

Many people instinctively associate mucus with something disgusting, but in fact, it has incredibly many valuable functions for our health. It keeps track of our important intestinal flora and feeds the bacteria. It covers all internal surfaces of our body, and, as a barrier to the outside world, it helps us protect ourselves from infectious diseases.

This is because mucus acts as a filter that keeps the bacteria in or out, and the bacteria feed on the sugars in the mucus between meals. So, if we can produce the mucus that is already present in the body with the right sugars, it might be used in brand new medical treatments.

Now, researchers from the DNRF Centre of Excellence, Copenhagen Center for Glycomics, have discovered how to artificially produce the healthy mucus.

'We have developed a method for producing the important information found in human mucus, also called mucins, with their important sugars. Now, we show that it is possible to artificially produce it in the same way as we produce other therapeutic biologics today, such as antibodies and other biological medicine', says Professor Henrik Clausen, lead author of the study and Director of the Copenhagen Center for Glycomics.

The mucus, or mucins, consist mostly of sugars. In the study, the researchers show that it is actually special patterns of sugars on the mucins that the bacteria recognise.

'It is the body's way of selecting the good bacteria and deselecting those that cause diseases. And it is precisely the sugars in the mucus that we are now able to design as needed', says first author of the study, Ph.D. student Rebecca Nason.

The researchers are particularly interested in the mucus in the gastrointestinal tract. Like a giant fishing net, the mucus keeps track of all the bacteria, our microbiome, down there. So, if one could imitate the ability of bacteria to attach to the intestinal mucus, one could design oral medications that stick to the mucus, making them more effective.

'We have found a small molecule from bacteria - which we call X409 - that binds to the intestine, and that is precisely one of the many possibilities we are now working on', says Rebecca Nason.

It can be difficult to get medicine to be effective when it has to be ingested and absorbed into our intestinal system. So, when you design your drug as a pill that the patient swallows, it is not certain that it will be fully efficient.

There are many obstacles on the way down through the digestive system, and the medication needs time in the gastrointestinal tract to be dissolved and distributed in the body', explains Rebecca Nason.

We swallow more than a litre of mucus in the form of saliva per day and more from the stomach, which together with the ever-changing fishing net of mucus in the intestine feed our intestinal microbiome. The microbiome of the intestine is absolutely crucial to our health and of great importance in relation to many diseases.

'An incredible number of diseases have a connection to the intestinal flora, but we still know very little about how we can control the intestinal flora in the treatment of diseases. This is where synthetic mucins could open up new treatment options', says Associate Professor Yoshiki Narimatsu, another of the lead authors of the study.

'Ultimately, one can imagine using mucins as a pre-biotic material, that is, as molecules that help the good bacteria in the body', says Yoshiki Narimatsu.

With artificial mucus, it will also be possible to alleviate infections in the body. Mucus in saliva flushes out bacteria and cleans the oral cavity, and mucus constantly runs down over our eyes and keeps them clean.

'We imagine that instead of using antibiotics, you might produce for example eye drops with the mucin that normally removes the bacteria in the treatment of eye infections. In concrete terms, this means that mucin can dissolve the so-called biofilm of bacteria, which is often pathogenic', says Yoshiki Narimatsu.

Biofilm is a film of bacteria on the surface of a material and is, among other things, what you can feel on your teeth if it has been a long time since you last brushed them.

It is not only bacteria that recognise mucins.

'We also show that mucins are very important for the way in which the common flu virus infects our mucous membranes in competition with mucins which inhibit the infection and flush out the virus', says Yoshiki Narimatsu.

Unlike the covid-19 virus, influenza virus binds to a sugar, which is found on all mucins, and a sugar has already been developed for treatment of the flu.

'We hope mucins may work even better', says Yoshiki Narimatsu.

COLUMBUS, Ohio - Female vampire bats establish an egalitarian community within a roost rather than a society based on a clear hierarchy of dominance that is often seen in animal groups, a new study suggests.

Researchers observed more than 1,000 competitions for food among a colony of 33 adult female bats and juveniles living in captivity, assigning a rank to each bat based on a calculation of wins and losses in those contests.

The team found that, unlike in many mammal societies, the higher-ranking animal didn't necessarily win every bout over food, and there was a randomness to the ranking order - no specific quality they measured gave a bat a better chance at dominance, so any adult female had an equal opportunity to rank very high or very low on a scale of dominance in the roost.

Traditionally, research on group-living animals - especially primates - in the wild has focused on how a dominance structure factors into survival, longevity and healthy offspring, and only later considered the importance of friendship in those same communities.

Senior study author Gerald Carter has worked in reverse order. His research on highly social female vampire bats, whose behaviors resemble what's been observed in some primate groups, has focused on cooperation, finding that vampire bats make "friends" through a gradual buildup of trust and show signs of maintaining those friendships in the wild.

"We realized we don't know anything about dominance among female vampire bats, so this is a first step in the direction of trying to identify how similar they are to primates in this way," said Carter, assistant professor of evolution, ecology and organismal biology at The Ohio State University. "We can say quite clearly that they're definitely not like some of the well-studied primates. They don't have a very clear social rank that they're constantly enforcing."

The study is published today (July 7, 2021) in the journal Royal Society Open Science.

The research team video-recorded 1,023 competitive interactions concerning food over three months in a captive colony of common vampire bats at the Smithsonian Tropical Research Institute (STRI) in Panama. The colony consisted of 24 adult females captured from two distant sites as well as nine young bats - four males and five females.

Winners and losers were identified from five types of events at the blood-meal feeders: displacement of a feeding bat by an intruding bat with or without physical contact; a feeding bat's maintenance of its position following an approach by another bat, with or without contact; and a nearby bat waiting to eat until after a feeding bat leaves the feeder.

Researchers assigned social rank to individual bats based on wins and losses and found widespread variability in adult female bat rankings, with essentially no predictors for how these community arrangements played out. No associations were found between body size, age and reproductive status and dominance ranking, and common vampire bat behaviors of grooming and sharing food were not associated with social rank. Being related to each other had no effect. The only possible predictor detected, when male juveniles were excluded, was smaller forearms in the more dominant adult females.

When compared to data that exists on communities of female yellow baboons and female long-tailed macaques, the vampire bats were also far less likely to show a consistent pattern of wins by the more dominant community members.

"Basically, with these primates, almost 100% of the time the dominant individual wins," Carter said. "With vampire bats, even when you have two individuals that are 10 rankings apart, the more dominant individual is not necessarily displacing the other one."

The findings suggested that young males are subordinate to adult females, and the same is likely to be true for adult males because they are smaller than female vampire bats. Previous research has shown that male vampire bats do compete with each other and fight - and within a colony, males tend to focus on establishing territory rather than carrying on social relationships.

A comparison of group-level dominance measures between female vampire bats and 14 other documented female mammal groups - including African elephants, bison and numerous primates - placed the bats as either 12th or 15th in the overall dominance ranking, depending on the metric used.

Though the single study of animals in captivity doesn't provide all the answers, the research does suggest vampire bats live in communities that are "more fluid and open," Carter said. A fluid and open society is different from, but not necessarily better than, a group characterized by dominance and hierarchy, he noted. A clear power structure actually helps prevent conflict.

"In a group of animals that's always together, it's really important to work out who's dominant, because when you come across food, you all come across that food together," he said.

"With vampire bats, they have this society inside of a tree, and all of the relationships are worked out. But we think vampire bats don't hunt as a stable group - they go out and forage, and come back together. So what that means is that they're not always coming across a food resource together and having to decide who's going to get access to it first."

Driving through a tunnel is a challenging and risky task. Drivers need to lower their speed and adapt to poor light, while the enclosed space may make them anxious. Preventing accidents is a public health challenge that uses insights from engineering, psychology, physiology, and neuroscience. Here, in a virtual reality (VR) study in Frontiers in Psychology, scientists from China, Canada, and the USA show that playback of slow music inside tunnels can reduce tension and fatigue in drivers, making them less prone to speeding and overtaking. These results imply that well-chosen background music can help improve road safety.

"When drivers go through a tunnel, they need to process a large amount of information quickly. We wanted to find the best way to use sound to keep drivers alert and focused inside tunnels. We here compare the effect on brain activity and physiology of different types of sound: slow versus fast music, warning sounds such as sirens, and a voice reminding them to drive safely," says corresponding author associate professor Yanqun Yang from the Transportation Research Center in College of Civil Engineering at Fuzhou University, China. "We show that the best solution is to play slow music inside the tunnel, but to play alarming sounds like sirens at the entry and exit or during emergencies."

Rate of accidents depends on location within tunnels

Previous research has found that accidents are less frequent in tunnels than on open roads, but that accidents that do happen inside tend to be more serious. Nor is the rate of accidents the same along a tunnel's length: for example, accidents are more likely just before or after the entrance. Once drivers are acclimatized to the special environment inside, they tend to reduce speed and move away from the tunnel wall, causing the rate of accidents to decrease. Accidents become more likely again over the middle stretch in long tunnels, because drivers may relax their vigilance from boredom.

The authors here studied whether background sounds and music might help to keep drivers relaxed but focused over the length of a long tunnel. With immersive VR, they simulated a 5100-m-long four-lane tunnel with traffic in both directions, driving between 80 and 100 kmph. They recruited 40 young women and men to act as experimental drivers - these people watched the VR on screens while inside a console that continuously recorded the pressure on the pedals, the steering wheel's angle, driving speed, and acceleration.

Yang et al. used wireless sensors to compare the drivers' neurophysiological response to five experimental sounds: a recording from a real tunnel, the slow music song "Canon" with 72 beats per minute (bpm), the fast song "Croatian rhapsody" with 96 bpm, a police siren, and a female voice warning "Please turn on the lights, slow down, and no-overtaking" or "Here is an accident blackspot, please turn on the lights and slow down."

They measured skin electrical conductance as a proxy for 'arousal', which encompasses attention, vigilance, and memory storage. Measures of heart rate and its variability served as proxies for emotional state, stress, mental load, and fatigue, while EEG measures of the brain's activity were used as proxies for wakefulness, fatigue, relaxation, and nervousness.

Slow music stimulated drivers to drive safely

Drivers drove fastest in response to fast music, and slowest in response to slow music. Comparisons of heart rate variability - typically low in people who are stressed - indicated that the drivers felt most relaxed, with a minimal mental load, when listening to slow music. This was consistent with feedback from drivers, of whom 63% chose the slow music as their preferred background.

Comparisons of the drivers' β brain waves - typically elevated in persons who are nervous or excited, and hence prone to fatigue - indicated that slow music reduced nervousness in the drivers, while voice prompts, fast music, and sirens increased it. Comparisons of the relative patterns of α, β, and θ waves - often combined in research to yield measures of fatigue - indicated that the voice prompt was most effective in preventing tiredness.

Best solution: combination of slow music with occasional sirens

The authors conclude that safety would increase if slow music would be played as a background in tunnels, while sirens should be played only at the entry, exit, and during emergencies.

"We find that slow music played as background throughout the tunnels, replaced by sirens only at spots and times when the risk of accidents is highest, is best to keep drivers alert, at ease, and not tired, while stimulating them to be extra vigilant and focused when needed," says coauthor Dr Wei Lin from the Department of Civil and Architectural Engineering and Construction Management at the University of Cincinnati, USA.

"There still a long way to go before more specific design and management recommendations can be proposed. For example, future studies should test the effect of a greater range of sounds on drivers who differ in age, driving experience, hearing sensitivity, and degree of fatigue. But our study is a proof of principle, which pushes our knowledge on road safety a step forward."

How do predators know to avoid brightly-coloured toxic prey? A collaboration of researchers has put social information theory to the test in a reliable real-world system to find the answer - by copying what others do, or do not, eat.

An international team of researchers from Finland, New Zealand, Colombia and the U.K. have provided the first evidence that wild birds can learn to avoid distasteful prey by observing what others eat.

"We've known for a long time that predators, like birds, associate brightly coloured warning signals with the danger of eating certain prey types. However, we've never been able to demonstrate in the wild how predators learn about these aposematic prey advertisements. If predators do not recognize the signal, then the prey are highly vulnerable to naive predators. This is a big problem that prey face each year when juvenile predators arrive. Since aposematism is widespread in nature, we wanted to solve this problem in a real-world setting" explains one of the lead-authors Rose Thorogood, now at the University of Helsinki.

At the established Madingley Wood field site in Cambridgeshire, UK, Liisa Hamalainen, a doctoral student at the University of Cambridge, used an innovative combination of field experiments and social network analyses to investigate the capacity for social information transmission among bird predators and identified potential implications for predator-prey coevolution. The team's results offer solutions to evolutionary problems in predator-prey dynamics and support theoretical predictions from social learning theory. But more broadly, the research speaks to the role of social information amidst the powerful dynamics of ecology and evolution, and hence opens the door to new studies in other coevolutionary systems.

According to this experiment, one avenue is through social learning. The researchers set up pairs of bird-feeders within the Madingley Wood field site. One feeder would dispense brightly-dyed almond flakes that were left naturally tasty (undefended prey). The other would dispense differently-coloured almond flakes with additives to make them disgustingly bitter (aposematic prey). Local blue tits (Cyanistes caeruleus) and great tits (Parus major) could gather around the feeders and take their pick of food, but also observe the feeding attempts of others.

In between the experimental sessions, the feeders dispensed plain, uncoloured almond flakes. During this time, the researchers used RFID to record predator visits to the feeders. Will Hoppitt, a statistical consultant from Royal Holloway University of London, then generated a social network based on the likelihood for individuals to forage together, and compared this to the patterns observed in the birds' choices of coloured almonds.

The analysis showed that birds could learn to avoid the bitter almonds within eight days, with adults being quicker to learn than the juveniles. Importantly, information about the bitter almonds appeared to flow through the predicted social links, especially from adults to juveniles. This offers a solution to the problem of naive predators, as they can learn by watching the behaviour of others instead of through trial-and-error. Thereby, the selection pressures exerted on their aposematic prey are reduced.

"These results greatly extend the current state of our knowledge gained from studying predator learning under controlled lab conditions. It demonstrates that social interactions both within and across species allow predators to learn very quickly, and in turn allow aposematic prey types to persist across naive predator generations. This highlights that social information transmission is likely to play a critical role in eco-evo dynamics and in many other coevolutionary systems, including host-parasite and plant-pollinator relationships. It's exciting to see what we can find from further field-based as we dive deeper into understanding the social layers of coevolutionary processes" Thorogood sums up.

Dancing with music can halt most debilitating symptoms of Parkinson's disease

First-of-its-kind York U study shows participating in weekly dance training improves daily living and motor function for those with mild-to-moderate Parkinson's

TORONTO, July 7, 2021 - A new study published in Brain Sciences today, shows patients with mild-to-moderate Parkinson's disease (PD) can slow the progress of the disease by participating in dance training with music for one-and-a-quarter hours per week. Over the course of three years, this activity was found to reduce daily motor issues such as those related to balance and speech, which often lead to social isolation.

Joseph DeSouza, senior author, principal investigator and associate professor in the Department of Psychology at York University and PhD candidate Karolina Bearss, found people with Parkinson's (PwPD) who participated in weekly dance training, had less motor impairment and showed significant improvement in areas related to speech, tremors, balance and rigidity compared to those who did not do any dance exercise. Their data showed significant improvements in experiences of daily living, which include cognitive impairment, hallucinations, depression and anxious mood such as sadness. The study showed overall that non-motor aspects of daily living, motor experiences of daily living, motor examination symptoms and motor complications did not show any impairment across time among the dance-trained PwPD group compared to PwPD who do not dance.

The study is the first of its kind to follow PwPD over a three-year period during weekly dance participation with music, providing additional information regarding the nature of progression of motor and non-motor PD symptoms.

"The experience of performing and being in a studio environment with dance instructors appears to provide benefits for these individuals," said DeSouza. "Generally, what we know is that dance activates brain areas in those without PD. For those with Parkinson's disease even when it's mild motor impairment can impact their daily functioning -- how they feel about themselves. Many of these motor symptoms lead to isolation because once they get extreme, these people don't want to go out. These motor symptoms lead to further psychological issues, depression, social isolation and eventually the symptoms do get worse over time. Our study shows that training with dance and music can slow this down and improve their daily living and daily function."

The goal of the research was to create a long-term neurorehabilitation strategy to combat the symptoms of PD. In the study, researchers looked at how a multi-sensory activity, (like dance with music learning) which incorporated the use and stimulation of several sensory modalities in the dance environment including vision, audition, tactile perception, proprioception, kinesthesia, social organization and expression, olfactory, vestibular and balance control -- may influence many of the mood, cognitive, motor and neural challenges faced by PwPD.

Researchers followed collected data from PwPD over three-and-a-half years while they learned choreography over the first year and performed it, that is designed to be adaptable to the disease stage and current symptoms for PwPD.

In the study, 16 participants with mild-to-moderate PD (11 males, five females) with an average age of 69, were tested between October 2014 and November 2017. They were matched for age and severity of disease. Each participant took part in a 1.25-hour dance class at Canada's National Ballet School (NBS) and Trinity St. Paul's church locations. Dancers participated in dance exercises which provided both aerobic and anaerobic movements. This group was then compared to 16 non-dance PwPD participants (the reference group) chosen from a larger PwPD cohort from the Parkinson's Progression Marker Initiative (PPMI), a longitudinal research project funded by the Michael J. Fox Foundation for Parkinson's Research (MJFF) and related funding partners.

Classes began with live music accompaniment during the seated warm-up, followed by barre work, and ended with moving across the floor. All participants learned choreography for an upcoming performance. Researchers recorded videos, conducted paper and pen questionnaires of all participants and performed statistical analyses.

"Dance is so complex, it's a multi-sensory type of environment," said Bearss. "It incorporates and stimulates your auditory, tactile, visual and kinesthetic senses and adds an interactive social aspect. Regular exercise does not offer these aspects. There's so much more to dance."

Researchers will next examine what occurs in the brain immediately before and after a dance class to determine what neurological changes take place.

"Currently there is no precise intervention with PD and usual remedies are pharmacological interventions, but not many options are given for alternate exercises or additional interventions to push their brains," said DeSouza. "Hopefully this data will shed light on additional therapies for this group and be used in the treatment process. There may be changes in the brain that occur with dance with music, but more research is necessary."

When a head of state or government official travels to another country to meet with his/her counterpart, the high-level visit often entails a range of public diplomacy activities, which aim to increase public support in the host country. These activities often include events such as hosting a joint press conference, attending a reception or dinner, visiting a historic site, or attending a social or sports event. A new study finds that public diplomacy accompanying a high-level visit by a national leader increases public approval in the host country. The findings are published in the American Political Science Review.

"Bilateral meetings provide world leaders with a forum to talk about the real issues; yet, a visiting national leader will also often spend a significant amount of time on image building, as the visiting country strives to improve its image around the world," says co-author Yusaku Horiuchi, a professor of government and the Mitsui Professor of Japanese Studies at Dartmouth.

"The simple fact that time and money is allocated for image-building activities as part of these high-level visits suggests that many countries actually think that these public diplomacy campaigns matter. Yet, until now, there has been little, if any, well-identified causal evidence," says Horiuchi. "Our study is the first to show the effectiveness of public diplomacy and how it can shape foreign public opinion."

For the study, political scientists from Dartmouth, the Australian National University and Florida State University examined data on high-level visits by 15 leaders from 9 countries over 11 years (from 2008 to 2018). Eighty-six visits by nine major countries -- Brazil, Canada, China, Germany, India, Japan, Russia, the U.K., and the U.S. -- were analyzed. The team obtained data on the high-level visits and combined it with Gallup World Poll data to examine how public opinion of a visiting leader changes from five days before the visit to five days after the visit.

Through a statistical analysis, the results show that public approval of a visiting leader's job performance increases on average by 2.3 percentage points when the leader visits a foreign county. As the researchers explain, the effect on public opinion does not fade immediately, as it lasts up to two and a half weeks and is especially strong when public diplomacy events are covered by the news media. This effect is also especially large when a new leader visits another country during their first year in office, a phenomenon that the researchers call the "soft-power honeymoon" effect. When a new leader visits another country, the effect on the public's approval rating of the leader is double that of a leader who has been in office for five years or more.

The researchers found that the effect on public opinion is much stronger for the visiting leader rather than for the host leader, illustrating that there was no "coattail" effect: host leaders do not leverage popular visitors to boost their own approval ratings.

"Our results suggest that 'soft power,' a term coined by Joseph Nye referring to a country's ability to influence international outcomes by attraction and persuasion rather than by coercion or payment, can impact foreign public opinion," says Horiuchi.

As part of the analysis, the researchers examined the power ratios between the visiting and host countries based on data from the Correlates of War Project. The data shows that public diplomacy's effect on public approval in a host country is not conditional on the balance of military power, also known as "hard power," between the two countries. The findings provide evidence that soft power is independent of hard power and as the researchers conclude, public diplomacy should not be dismissed as merely a performance.

Data from nine cities in Mexico confirms that identifying dengue fever “hot spots” can provide a predictive map for future outbreaks of Zika and chikungunya. All three of these viral diseases are spread by the Aedes aegypti mosquito. 

Lancet Planetary Health published the research, led by Gonzalo Vazquez-Prokopec, associate professor in Emory University’s Department of Environmental Sciences. The study provides a risk-stratification method to more effectively guide the control of diseases spread by Aedes aegypti. 

“Our results can help public health officials to do targeted, proactive interventions for emerging Aedes-borne diseases,” Vazquez-Prokopec says. “We’re providing them with statistical frameworks in the form of maps to guide their actions.” 

The study encompassed data for 2008 through 2020 from cities in southern Mexico with a high burden of dengue fever cases during that period, along with cases of the more recently emerged diseases of Zika and chikungunya. The cities included Acapulco, Merida, Veracruz, Cancun, Tapachula, Villahermosa, Campeche, Iguala and Coatzacoalcos. 

The results found a 62 percent overlap of hot spots for dengue and Zika and 53 percent overlap for cases of dengue and chikungunya. In addition, dengue hot spots between 2008 and 2016 were significantly associated with dengue hotspots detected between 2017 and 2020 in five of the nine cities. 

The work builds on a previous study of the spatial-temporal overlap of the three diseases, focused on Merida, a city of one million located in the Yucatan Peninsula. That study showed that nearly half of Merida’s dengue cases from 2008 to 2015 were clustered in 27 percent of the city. These dengue hot spots contained 75 percent of the first chikungunya cases reported during the outbreak of that disease in 2015 and 100 percent of the first Zika cases reported during the Zika outbreak of 2016. 

“In this latest paper, we’ve expanded our analysis in scope and geography and shown that the findings are consistent across these nine cities of different sizes and in different regions,” Vazquez-Prokopec says. “We’ve confirmed that dengue, Zika and chikungunya outbreaks tend to concentrate in small areas of a city, and that these hot spots are predictive of where future cases will concentrate.” 

Mosquito control efforts generally involve outdoor spraying that covers broad swaths of a city, but the Aedes aegypti mosquito has adapted to live inside houses. Work by Vazquez-Prokopec and collaborators has shown that the best way to control these mosquitos and the diseases they spread is by spraying a long-lasting pesticide indoors — on the ceilings, along the bases of walls, and in other areas of homes where the mosquitos tend to cluster.

This approach — known as targeted indoor residual spraying — is too expensive and time-consuming to apply across a city. 

The statistical framework in the current paper, however, allows public health officials to concentrate their efforts on previous hot spots for Aedes-borne diseases to better control — and even prevent — outbreaks. 

“The ultimate goal is to give public health officials the power to harness big data and do more effective and efficient mosquito control — even before an epidemic begins,” Vazquez-Prokopec says. 

Vazquez-Prokopec is currently leading a consortium in a randomized clinical trial in Merida to test targeted indoor residual spraying as an intervention against Aedes-borne diseases. The five-year trial, launched in 2020, is funded by a $6.5 million grant from the National Institutes of Health. 

Dengue fever is sometimes called “break-bone fever” due to the excruciating pain that is among its symptoms. More than one third of the world’s population lives in areas at high risk for infection with the dengue virus, a leading cause of illness and death in the tropics and subtropics.

Dengue is endemic through most of Mexico, where between 75,000 and 355,000 cases occur annually, translating into an economic cost of between about U.S. $150 million and $257 million annually. 

Chikungunya is rarely fatal but the symptoms can be severe and debilitating. Zika can cause symptoms similar to those of dengue and chikungunya, such as joint pains and fever. While Zika tends to be less debilitating, or even asymptomatic, if a pregnant woman contracts the virus it can have a catastrophic impact on her unborn child, including severe brain defects. 

Research conducted at Cruzeiro do Sul University in São Paulo, Brazil, can contribute to earlier diagnosis of diabetic neuropathy, a disorder characterized by damage to peripheral nerves, with symptoms such as pain and paresthesia (pricking, burning and numbness), mainly in the legs and feet.

In the study, a group led by Professor Paulo Barbosa de Freitas Júnior measured grip force in diabetic patients while they were holding and handling objects. The results were compared with data for healthy subjects and patients with other neurological diseases, such as multiple sclerosis, Parkinson’s, and carpal tunnel syndrome (pain, numbness and tingling in the hand and arm caused by a pinched nerve in the wrist).

Freitas and his group tested volunteers to measure the grip force exerted by diabetics with and without a diagnosis of neuropathy, as well as healthy subjects, and developed a methodology that can be used to produce equipment for use in clinical practice. In future, the innovation should help physicians diagnose the disorder quickly and easily not long after the onset of initial symptoms of neuropathy in diabetics.

The analysis focused on grip force used to hold and manipulate objects, and on relative safety margin, i.e. grip force normalized by the coefficient of friction between skin in contact with the object and surface of the manipulated material. The central nervous system “calculates” the amount of force needed to hold an object, learning to do so better over time. “Every object has a contact surface with which our fingers create friction when we hold it. The smoother the surface, the more grip force needed to hold it. If it’s rough, we can use less grip force thanks to friction,” Freitas explained.

Considering grip force and safety margin, people with neurological disorders such as multiple sclerosis and Parkinson’s tend to use more force to grip objects than healthy people. The force needed to manipulate an object is moderately greater than the minimum force needed to hold it in the desired position. “In the case of people with neurological alterations, our hypothesis is that they grip objects more strongly as a conservative strategy,” Freitas said. “The nervous system detects a neurological deficiency and sends a command for the hand to use more force as it grips the objects. This process is entirely unconscious, of course.”

The test results showed that healthy volunteers used between 100% and 120% of the minimum force required to hold an object, whereas the force used by participants with neurological alterations was two and a half times to three times greater.

Freitas and his team then investigated the performance of diabetics, who typically suffer from neuropathy as the disease worsens. “There was no prior research on diabetics involving the type of experiment we used in our study,” he said.

The hypothesis was that diabetics would grip objects more tightly, as is the case with people who suffer from carpal tunnel syndrome, multiple sclerosis and Parkinson’s. “However, what we found was the opposite: diabetics used half as much force to hold an object as controls in the simplest task, which was the static test, in which the subject merely has to hold an object without manipulating it,” Freitas said.

An article published in the journal Human Movement Science reports the main findings of the study, which was funded by FAPESP via a Regular Research Grant and a scientific initiation scholarship.

Calculating grip force

Three types of test were conducted with 36 volunteers, including 24 diabetics divided into two groups: 12 who had developed neuropathy, and 12 who had neither been diagnosed with neuropathy nor displayed clinical signs of the disorder. The other 12 participants were healthy and formed the control group. Before testing began, the researchers measured each participant’s skin sensitivity, since the sense of touch is a key factor in conveying to the central nervous system the information required by the brain to calculate the force needed to hold and manipulate objects.

Volunteers were each asked to perform three tasks using the same type of object instrumented to measure force. In the static holding test, they had to hold the object with their dominant hand as if they were holding a glass of water. A beep sounded after ten seconds, and they were to unclasp their fingers slowly so as to release the object, while a researcher measured the friction between the fingers and the object. The second task consisted of picking up an object from a table, lifting it about 5 cm, holding it for 10 seconds, and putting it back on the table. In the third task, termed oscillation, the volunteers had to grasp the object, hold it in front of their navel, and move it about 20 cm up and down for 15 seconds.

In the second and third tasks, the results for diabetics and diabetics with neuropathy were similar to those for controls. The surprise came in the simplest task of all, which was static holding, as diabetics and diabetics with neuropathy used half the force applied by the controls.

The explanation is not exactly a loss of sensitivity in the fingers of diabetics, the researchers explained, but deficient tactile information sent from their fingertips to the central nervous system. There is not enough information of high quality for the brain to make the requisite calculations and the hand to use the right amount of force. “In addition, there are studies showing that certain areas of the spinal cord and cortex that receive and process this sensory information are smaller in diabetics than in healthy people,” Freitas said.

The study suggests diabetes does not only affect the periphery of the body, causing loss of sensitivity in the toes and fingers, for example, but also affects the central nervous system. “This happens early in diabetes. People tend to think these complications happen only after a certain age or when a person has had diabetes for some time, but actually patients have the problem before neuropathy is diagnosed,” Freitas said.

Novel device for rapid early diagnosis

Scientists do not fully understand what causes neuropathy in diabetics. One hypothesis has to do with neuron death or loss of function due to alterations in blood vessels and metabolism. “Because of metabolic alterations, blood doesn’t reach the nerve ends in the soles, palms, toes and fingers, leading to the death of neurons in these peripheral regions,” Freitas surmised. As the disease progresses, neurons in other regions closer to the torso, knees and so on, also suffer damage and may die.

Given this lack of knowledge, prevention is the best option, and the study discussed here will help in this regard, according to Freitas. “Our research provides a foundation on which a simple device could be developed for use in the doctor’s office with rapid results,” he said. Grip and load force can serve as behavioral biomarkers to detect neurological alterations even before the patient manifests clear symptoms of neuropathy. “The idea is to have a device that enables physicians to measure force in a straightforward test and see if the patient shows signs of incipient neurological alterations.”

Neuropathy is currently diagnosed by means of a painful invasive examination using a technique called electroneuromyography, in which an electric current is passed through small electrodes in the shape of needles inserted into the patient’s muscles and the reaction time is measured to assess nerve conduction velocity. Freitas proposes a procedure that can be used during a regular visit to the doctor. The patient would hold an object instrumented to measure grip force. “After 10 to 15 seconds of this test, the physician would have the result: the object was held with this or that level of force, and the value measured is below or above the level considered safe to the act of holding the object. It could evidence neurological alterations arising from diabetes,” he said.

The next steps envisaged by Freitas include developing the instrumented object for use in such testing, which could be simpler than the one used in research. To do so, he needs to determine the best combination between the object’s weight and surface smoothness or roughness, so as to evidence the difference between diabetics and nondiabetics. “We need various combinations of smoothness and roughness, as well as lighter and heavier weights, in order to measure the differences between the combinations, and choose the best for use in future tests,” he said. He is pursuing partnerships with hospitals and companies interested in participating in the development of a solution, as well as volunteers for forthcoming studies. He can be contacted at Paulo.deFreitas@cruzeirodosul.edu.br or defreitaspb@gmail.com.

Immunologists at St. Jude Children's Research Hospital have identified a biological pathway that selectively controls how key immune cells, called T follicular helper cells, mature into functional components of the immune system.

The finding offers the promise of developing drugs to activate the metabolic pathway to enhance the effectiveness of vaccines, including those that protect against COVID-19. Such medications could stimulate the immune system to respond more vigorously following immunization to produce more antibodies against a virus or bacterium.

The work also lays the foundation for drugs that dial down the pathway to alleviate autoimmune diseases such as lupus. In such disorders, an overactive immune system produces antibodies that attack the body's own tissues.

Led by Hongbo Chi, Ph.D. of the Department of Immunology, the researchers published their findings today in Nature.

Regulating the adaptive immune response

Chi and colleagues identified a metabolic control pathway that selectively regulates the development of specialized immune cells in the adaptive immune system. These cells are called T follicular helper cells.

The adaptive immune system is so named because when the body is infected by viruses or bacteria, it learns to target and attack them. T follicular helper cells activate the component of the adaptive immune system called humoral immunity. While humoral immunity attacks invaders circulating outside cells largely via the generation of antibodies, the other adaptive immune system component, cellular immunity, targets invaders inside infected cells.

In their experiments, the researchers sought to discover whether a metabolic control pathway existed that modified the T follicular helper cells to activate them. When such cells are activated, they help antibody-producing cells, called B cells, to mature and to generate infection-fighting antibodies.

Discovering a key pathway

To discover a possible control pathway, Chi and his colleagues used genetic techniques to delete in the T cells multiple enzymes known to be elements of such metabolic control pathways. Then, the scientists introduced the deletion-engineered T cells into mice followed by infection with a virus and tested whether the T cells lacking the enzyme were functional.

Their experiments revealed that one metabolic control pathway, called the CDP-ethanolamine pathway, selectively regulated the T follicular helper cells.

"This finding was a big surprise," Chi said. "First of all, this pathway was considered to have a housekeeping function leading to the production of building blocks for the cell membrane. But we discovered that it has a major signaling function. And secondly, we were surprised that this pathway--and not other parallel pathways of this type--was the only one involved in regulating T follicular helper cells."

As a complementary method to determine if the pathway selectively regulated the T follicular helper cells, the researchers deleted each of the key enzymes they identified in the CDP-ethanolamine pathway. They found that deletion of these enzymes, but not those of other parallel regulatory pathways, selectively impaired development of the T follicular helper cells, but not overall immune function.

Importantly, said Chi, those key enzymes could be targets for drugs that either enhance or inhibit the pathway, and thus the activity of the T cells.

"We are now exploring whether we can enhance the effectiveness of vaccines by using drugs that activate the pathway, to help these T cells mobilize the immune system to generate antibodies in response to a vaccine," he said.

"On the other hand, to treat autoimmune disease, we're interested in developing new ways to inhibit this pathway," he said. "This approach is promising because we know that such activation or inhibition is highly selective for T follicular helper cells and would not affect other immune functions."

The researchers are also delving into the structural mechanisms by which the enzymes work--insights that could offer such drug targets, Chi said.

ST. LOUIS -- In the United States, low-income and minority students are completing college at low rates compared to higher-income and majority peers -- a detriment to reducing economic inequality. Double-dose algebra could be a solution, according to a new study published in roceedings of the National Academy of Sciences of the United States of America (PNAS).

The paper, "Effects of Double-Dose Algebra on College Persistence and Degree Attainment," is the culmination of a series of studies that followed two cohorts of ninth-grade students over a period of 12 years in the Chicago Public Schools (CPS) where double-dose algebra was introduced in 2003.

The new policy required incoming ninth graders with eighth-grade math scores below the national median to complete two periods of math -- one period of algebra, plus an additional period of instruction designed to build foundational prealgebra skills. Research findings showed that, for median-skill students scoring at or above the 50th percentile in the 2003 cohort, double-dose algebra significantly increased semesters of college attended and college degree attainment.

"This provides unique insight for districts that provide extra instruction but are unable to rigorously study the impact of those programs," said Takako Nomi, Ph.D., associate professor of educational studies at Saint Louis University. Her work focuses on educational policy and equity.

Nomi, who also serves as research affiliate at the University of Chicago's Consortium on Chicago School Research, led the study. Other authors include Stephen W. Raudenbush, Ed.D., of the department of sociology at the University of Chicago; and Jake J. Smith, of Harris School of Public Policy at the University of Chicago.

A key takeaway from the study is how schools chose to implement the policy matters, Nomi said. Fewer schools adopted the cut-score-based double-dose algebra program in 2004 than in 2003. Most schools that did strongly comply in 2004, did so by placing their median-skill double-dose students in low-skill algebra classrooms, according to the study.

In terms of classroom peer composition, "the impact was largest when schools didn't group double-dose students with low-skilled students," Nomi said. Research findings demonstrate that when students were placed in double-dose classes with much lower-skilled peers, the program had no effect. Subsequent research should address the design of optimal policies for lower-skill students, Nomi said. A math intervention far more intensive than double-dose algebra is essential to improve their high school and postsecondary outcomes. The study also notes that ninth-grade students who fail math also tend to fail other core classes.

"It's not just a math issue," Nomi said. "The policy of giving extra math is not enough to change the trajectory for the students who struggle the most. It's important to support struggling students in general."

This study was supported by grant R305A170602 from the Institute of Education Sciences entitled, "Doubling Up? Understanding the Long-Term Effects of Ninth-Grade Algebra Reform on College Persistence and Graduation."

Nomi's research interests include urban education, education policy, inequality in education, school reforms, and college readiness. Nomi is associate director of the Sinquefield Center for Applied Economic Research where she collaborates with top SLU researchers. In a separate study, she's exploring why low-income and minority students -- particularly Black males -- are less likely to complete college. She is also a part of a faculty advisory board at SLU's Geospatial Institute.

"Equal pay for equal work," a motto touted by many people, turns out to be relevant to the plant world as well. According to new research by Stanford University ecologists, plants allocate resources to their microbial partners in proportion to how much they benefit from that partnership.

"The vast majority of plants rely on microbes to provide them with the nutrients they need to grow and reproduce," explained Brian Steidinger, a former postdoctoral researcher in the lab of Stanford ecologist, Kabir Peay. "The problem is that these microbes differ in how well they do the job. We wanted to see how the plants reward their microbial employees."

In a new study, published July 6 in the journal American Naturalist, the researchers investigated this question by analyzing data from several studies that detail how different plants "pay" their symbionts with carbon relative to the "work" those symbionts perform for the plants - in the form of supplying nutrients, like phosphorus and nitrogen. What they found was that plants don't quite achieve "equal pay" because they tend not to penalize low-performing microbes as much as would be expected in a truly equal system. The researchers were able to come up with a simple mathematical equation to represent most of the plant-microbe exchanges they observed.

"It's a square root relationship," said Peay, who is an associate professor of biology in the School of Humanities and Sciences. "Meaning, if microbe B does one-quarter as much work as microbe A, it still gets 50 percent as many resources - the square root of one-quarter."

When the researchers tested their equation against 13 measurements of plant resource exchange with microbe partners, they were able to explain around 66 percent of the variability in the ratio of plant payments to two different microbes.

"The biggest surprise was the simplicity of the model," said Steidinger. "You don't get a lot of short equations in ecology. Or anywhere else."

The fruit of frustration
When asked about the motivation for developing this equation, Steidinger summed it up with one word: frustration.

"There is a lot of really interesting literature in a field called 'biological market theory' that deals with how plants should preferentially allocate resources. But for the folks who actually run experiments, it is difficult to translate these models into clean predictions," said Steidinger. "We wanted to make that clean prediction."

An informal survey of the Peay lab members encouraged the researchers to start with the assumption of equal pay because most people agreed it was reasonable to guess that plants treat all microbes the same. To reach their final equation, Steidinger and Peay then factored in the diminishing returns seen in the fertilizer models and assessed them through the lens of biological market theory literature - which uses human markets as a mathematical analogy for exchanges of services in the natural world.

"It turns out if the plant is flush with resources - in this case, the sugars it feeds to its microbes - and if the nutrients are valuable enough, the plant pays its microbes according to a square-root law," said Peay.

The square-root model is a strong start to addressing Steidinger's original frustration but it is not quite at the level of realism he wants to eventually achieve.

"For instance, our model allows a useless microbe to be fired without the plant losing resources," said Steidinger. "But, just as in the human world, it takes an investment to hire a microbe and that initial investment is a gamble that microbial layabouts can consume at their leisure."

Weber's Law
In an attempt to explain why plants follow the square-root model, the researchers turned to a law in psychology. Weber's Law addresses how humans perceive differences in stimuli, such as noise, light or the size of different objects. It explains that, the stronger the stimuli, the worse we are at identifying when it changes. This law has been shown to hold for many non-human animals as well - describing, for example, how birds and bats forage for food and how fish school. Now the researchers suggest it's a good analogy for their plant payment scheme too.

"Our model says that plant should go easy on low-performing microbes, seemingly overpaying the 25-percent-as-good microbe with 50 percent as much resources," said Peay. "Well, it's long been known that humans and non-human animals sense differences in quantity in a way that might bias them towards similar leniency."

In other words, the researchers suggest that, like a human trying to detect the volumes of specific noises in a loud room, a plant making optimal payment decisions may be relatively insensitive to differences in the quality of its microbial employees. And the researchers argue that this insensitivity may be for the best, as it encourages plants to maintain a certain level of microbial diversity, which can help give the plant options for dealing with environmental changes it encounters throughout its lifetime.

"I think what we're seeing is plants behave like animals not because they have the same perceptional limitations - and certainly not because they think like animals - but because we face similar challenges in making the best choices when there are diminishing returns on investment," says Steidinger.

DURHAM, N.C. -- You dash into a convenience store for a quick snack, spot an apple and reach for a candy bar instead. Poor self-control may not be the only factor behind your choice, new research suggests. That's because our brains process taste information first, before factoring in health information, according to new research from Duke University.

"We spend billions of dollars every year on diet products, yet most people fail when they attempt to diet," said study co-author Scott Huettel, a professor of psychology and neuroscience at Duke. "Taste seems to have an advantage that sets us up for failure."

"For many individuals, health information enters the decision process too late (relative to taste information) to drive choices toward the healthier option."

The new paper, which appears July 5 in Nature Human Behaviour, describes the advantage taste has over healthfulness in the decision-making process.

"We've always assumed people make unhealthy choices because that's their preference or because they aren't good at self-control," said study co-author Nicolette Sullivan. "It turns out it's not just a matter of self-control. Health is slower for your brain to estimate - it takes longer for you to include that information into the process of choosing between options."

The research was undertaken when Sullivan was a postdoctoral associate at Duke. She is now an assistant professor of marketing at the London School of Economics and Political Science.

For the study, Sullivan and Huettel recruited 79 young adults of a median age of 24.4 years. Study participants were asked to fast for four hours before the experiment to ensure they arrived hungry.

Participants were asked to rate snack foods on their tastiness, healthfulness and desirability. They were then presented with pairs of foods and asked to choose between them - and the researchers timed their choices.

At the end of the experiment, participants were offered one of the foods they had chosen.

Study participants registered taste information early in their decision process - taking about 400 milliseconds on average to incorporate taste information. Participants took twice as long to incorporate information about a snack's healthfulness into their decisions.

That may not sound like much time. In many cases though, it's enough to alter the choice we make.

"Not every decision is made quickly - house purchases, going to college - people take time to make those choices," Huettel said. "But many decisions we make in the world are fast - people reach for something in the grocery store or click on something online."

The authors say their findings could apply to other choices, not just food. For instance, some financial decisions, such as saving and spending choices, may also be affected by how -
and when - the brain processes different types of information.

Meanwhile, all is not lost in the war against junk food cravings.

Half of study participants received a blurb before the experiment, stressing the importance of eating healthy. Those participants were less likely to choose an unhealthy snack.

The authors also identified something simple that can help people with their food choices: slowing down the decision-making process.

When study participants took longer to consider their options, they tended to pick healthier ones.

"There may be ways to set up environments so people have an easier time making healthy choices," Huettel said. "You want to make it easy for people to think about the healthfulness of foods, which would help nudge people toward better decisions."

When you insist you're not racist, you may unwittingly be sending the opposite message.

That's the conclusion of a new study* by three Berkeley Haas researchers who conducted experiments with white participants claiming to hold egalitarian views. After asking them to write statements explaining why they weren't prejudiced against Black people, they found that other white people could nevertheless gauge the writers' underlying prejudice.

"Americans almost universally espouse egalitarianism and wish to see themselves as non-biased, yet racial prejudice persists," says Berkeley Haas Asst. Prof. Drew Jacoby Senghor, one of the authors. "Our results suggest that the explicit goal of appearing egalitarian might blind people to the possibility that they could be communicating, and perpetuating, prejudicial attitudes."

Co-authored by Derek Brown, PhD 24, and Michael Rosenblum, PhD 20--a post-doctoral scholar at NYU Stern School of Business--the study builds on past research finding people's racial prejudice "leaks out" through nonverbal behavior, such as facial expressions or physical distance. In a series of experiments published in the Journal of Experimental Social Psychology, the researchers looked at perceptions based solely on written content.

They selected a group of white participants, screening out the small percentage who expressed overt prejudice, and scored subjects' racial attitudes with two widely used assessments. The subjects were then asked: "Do you believe that all people are equal and should have equality of opportunity? Why or why not?," and "Are you prejudiced toward Black people? Why or why not?" A second group of white participants, asked to read the written responses, accurately estimated how the writers had scored on the prejudice scale.

Linguistic cues

In a second experiment to parse out whether people were signaling racial attitudes intentionally or inadvertently, they asked one group to answer as honestly as possible and another group to answer "in the least prejudiced way possible." There was no difference to the readers, who accurately scored both groups' answers.

"That gave us some confidence that people are naturally trying to come across as egalitarian, but something about the language they choose is betraying them," Rosenblum said.

What were those linguistic cues? The most powerful indicator, they found, was language that dehumanized or objectified African Americans--for example, "I have a great relationship with the Blacks." Other characteristics such as defensiveness, references to personal responsibility, or a belief that equal opportunity exists were strongly associated with higher levels of prejudice, and cues such as focus on equity or an acknowledgement that inequality exists were associated with lower levels of prejudice. Interestingly, references to being colorblind or mentions of personal contact with Black people weren't indicative of the white participants' attitudes.

"This demonstrates that peoples' use of the cues are meaningful not only for how prejudice is expressed, but also how egalitarianism is perceived," said Brown.

Contagion effect

A third experiment had a sobering result. The researchers found that white participants reported greater prejudice towards Black people after reading statements from the self-avowed white egalitarians who scored high on underlying prejudice. In other words, the readers mirrored the attitudes of the writers, even when they identified themselves as ideologically dissimilar (conservative vs liberal).

"We don't know reading other people's views gave them permission to express more prejudice, or whether they thought that this is the norm and their actual prejudice level changed, but there seemed to be a contagion effect," Rosenblum said. "One of the lessons here is that words carry weight. It does seem that this is one way that prejudice is unwittingly spread."

FOR IMMEDIATE RELEASE

In what turned out to be one of the most important accidents of all time, Scottish bacteriologist Alexander Fleming returned to his laboratory after a vacation in 1928 to find a clear zone surrounding a piece of mold that had infiltrated a petri dish full of Staphylococcus aureus (S. aureus), a common skin bacterium he was growing.

That region of no bacterial growth was the unplanned birth of a medical miracle, penicillin, and would lead to the era of antibiotics. Now, in a paper published today in the journal Science Translational Medicine, researchers at Johns Hopkins Medicine have announced another accidentally discovered, potentially game-changing treatment -- one that may one day provide an alternative immune-based solution to the danger of antibiotic-resistant bacterial infections.

And like Fleming's surprise finding, the bacterium of note is once again S. aureus -- but this time, methicillin-resistant Staphylococcus aureus, the life-threatening strain unharmed by methicillin and other antibiotics, and better known by its acronym, MRSA.

The paper's senior author, Lloyd Miller, M.D., Ph.D., former professor of dermatology, infectious diseases and orthopaedic surgery at the Johns Hopkins University School of Medicine, and now with Janssen Research and Development, says the research team was originally intending to study the mechanisms behind MRSA skin infections in mice with and without the ability to manufacture interleukin-1 beta (IL-1β). This protein, transformed into its active form by enzymes called caspases, enhances protective immunity by helping immune cells called neutrophils, monocytes and macrophages fight bacterial infections.

"We gave the mice a blocker of all caspases [pancaspase inhibitor], a compound known as Q-VD-OPH, thinking it would leave both sets of mice more vulnerable to MRSA infection," Miller says. "To our surprise, blocking caspases had the opposite effect, resulting in a rapid and remarkable clearing of the MRSA bacteria by keeping the immune cells alive and boosting their protective function."

Sensing they might have accidentally uncovered a means of fighting bacterial "superbugs," Miller and his colleagues conducted their latest study to confirm the unexpected finding was not a fluke.

The results were encouraging.

"A single oral dose of Q-VD-OPH decreased the size of MRSA skin lesions and rapidly cleared the bacteria compared with vehicle-treated [given the carrier solution without Q-VD-OPH] and untreated mice," says study lead author Martin Alphonse, Ph.D., a dermatology postdoctoral fellow at the Johns Hopkins University School of Medicine. "And surprisingly, the treatment worked whether IL-1β was present or not -- and without administering any antibiotics."

The researchers, says Alphonse, found that the pancaspase inhibitor reduces apoptosis -- one of three main methods the body uses to remove worn-out or damaged cells -- of neutrophils and monocytes, leaving them in plentiful numbers and better able to remove MRSA bacteria.

"It's like a fire department where older firetrucks are kept operating to help put out blazes, when otherwise, they would have been taken out of service," says Miller.

The researchers also saw enhanced necroptosis -- a second controlled cell death process similar to apoptosis -- of macrophages, which are mature monocytes.

"The destruction of macrophages by necroptosis releases large amount of tumor necrosis factor, or TNF, a protein that triggers bacteria-fighting immune cells to swarm into an infected area of skin," says Alphonse.

Finally, the researchers tested whether Q-VD-OPH in mice could have broader activity against two other dangerous skin bacteria, Streptococcus pyogenes (the cause of multiple diseases, including scarlet fever, necrotizing fasciitis and toxic shock syndrome) and Pseudomonas aeruginosa (often a threat to hospitalized patients on ventilators, with catheters or suffering wounds from surgery or burns). The targeting of the body's immune system against bacteria via pancaspase inhibition -- referred to as "host-directed immunotherapy" -- proved just as successful as it had been for MRSA.

"It was an accidental finding by Alexander Fleming that led to the golden age of antibiotics, but now that's nearing the end because of antibiotic-resistant bacteria," says Miller. "It seems fitting that another surprise in the lab could be the start of a second golden age, the use of host-directed immunotherapy."