Culture

Engineered protein inspired by nature may help plastic plague

image: Mutations of a PET hydrolyzing enzyme PET2 resulted in a 6.7 degrees C increase in thermal stability and a 6.8-fold increase in PET hydrolytic activity. Tm represents melting (denaturation) temperature and colors on enzyme structures show their surface charges (blue: positive, red: negative).

Image: 
NINS/IMS

Cheap to produce and long to degrade, plastic was once a manufacturing miracle. Now, plastic is an environmental plague, clogging landfills and choking waterways. A Japan-based research team has turned back to nature to develop an approach to degrading the stubborn substance. Similar to how a protein binds to cellulose in plants or to chitin in crustaceans to initiate decomposition, an engineered protein is on its way to binding to plastic particles in an effort to more efficiently break them down.

They published their results on June 29 in ACS Catalysis, a journal of the American Chemical Society.

"Polyethylene terephthalate (PET) is produced and used in large quantities in modern society due to its low cost and ease of processing," said paper author Ryota Iino, professor of the Institute for Molecular Science (IMS) in the National Institutes of Natural Sciences (NINS). "However, in recent years, from the perspective of realizing a sustainable society, the complete recycling of PET in industry and the removal of PET from the natural environment have become global issues. To resolve these issues, it is very important to understand how to degrade PET efficiently."

The researchers investigated and engineered an enzyme cloned from a library of genetic materials collected from nature. This enzyme -- called PET2 -- was found to facilitate the degradation of PET by accelerating the reaction between PET's chemical components and water.

Using single-molecule imaging analysis, the team found that the way the enzyme binds to the surface of PET actually limited the rate of degradation.

"We also revealed that by introducing positive charges on the surface of PET-degrading enzyme, the binding rate to the PET surface can be increased," Iino said.

The positive charges react favorably to the PET surface, so more of the enzyme can bind and more effectively degrade the PET. The researchers also found that while engineered PET2 showed high thermal stability and highest activity at 68 degrees Celsius -- slightly lower than most residential kitchen ovens can go -- it may be more effective at higher temperatures where PET's molecular bonds become more flexible and breakable.

"Our ultimate goal is to create a bacterium that can sense PET in the environment, move toward it, and degrade it," Iino said. Such a bacterium would then be able to turn the degraded PET into energy useful for other organisms, effectively acting as an automated recycling center for plastic. "In nature, chitin and cellulose are recycled in this way."

Iino is also affiliated with the School of Physical Sciences at The Graduate University for Advanced Studies (SOKENDAI). Other contributors include Akihiko Nakamura, Department of Applied Life Sciences, Faculty of Agriculture, Shizuoka University, and the Shizuoka Institute for the Study of Marine Biology and Chemistry; and Naoya Kobayashi and Nobuyasu Koga, Exploratory Research Center on Life and Living Systems (ExCELLS), NINS. Koga is also affiliated with IMS, NINS, and SOKENDAI.

The Leading Initiative for Excellent Young Researchers, the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Sumitomo Foundation, and the ExCELLS Special Collaboration Program supported this research.

Credit: 
National Institutes of Natural Sciences

Studies explore links between stress, choline deficiency, preterm births, and mental health

In two recent articles published in Schizophrenia Bulletin, Sharon Hunter, PhD, an associate professor in the University of Colorado School of Medicine Department of Psychiatry, and M. Camille Hoffman, MD, MSc, an associate professor in the University of Colorado School of Medicine Department of Obstetrics and Gynecology, along with their research group, have uncovered a potential link between choline deficiency in Black pregnant women in the United States and increased risk of developmental and behavioral issues that can evolve into mental illness later in their children’s lives.

The first article, published in November 2020, is a study, titled, “Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness.” The second, published last month and titled “Targeting Treatments to Health Disparities,” is a follow-up article delving more deeply into known healthcare disparities highlighted by the study results.

The studies are the result of more than 20 years of research by the group, which began with a general goal of understanding in utero risk factors of schizophrenia.

“At that time, there was a lot of discussion around the idea that mental illnesses like schizophrenia were tied to prenatal neurodevelopment,” Hunter says.

Early choline clinical trial

Choline is an essential nutrient that can be found in foods such as milk, red meats, and eggs. Based on previous studies of choline showing that it is vital for fetal neurodevelopment, including the development of inhibitory neurocircuits in the brain that are abnormal in individuals with schizophrenia and many of their family members, the group launched its first clinical trial in 2004. During the trial, they supplemented pregnant women with a specific form of choline called phosphatidylcholine, then monitored their children until the age of four. Phosphatidylcholine is less likely to cause side effects, such as stomach upset, associated with pure choline. The results of the trial showed that those inhibitory neurocircuits were functioning properly in more children from supplemented moms than in children whose mothers didn’t receive the supplement.

“It showed that mothers who had lower choline levels during the second trimester of pregnancy gave birth to babies who were more likely to have worse neurodevelopmental scores, which can be a marker for later mental illness or behavioral problems,” Hoffman says.

The ultimate goal was to uncover whether supplementing with choline could help prevent schizophrenia, but since the condition isn’t typically diagnosed until a patient is in their 20s, the group instead monitored for the some of the disease’s early indicators.

“We couldn’t follow these children for 20 years, but we could test them as children to see if they had problems with attention or withdrawal or aggression, which can be indicators not just of schizophrenia but of other mental issues as well,” Hunter explains.

Uncovering a racial health care disparity

After the first choline trial, the group conducted a follow-up study in which they measured choline levels in 183 pregnant women. Although the women were told about choline and the researchers suggested that they try to get more choline in their diets, they did not administer any choline supplements to the participants. It was during this study that the group noticed a demographic disparity: overall, choline levels were markedly lower in Black women than any other group.

“When we found these differences in choline levels, we started to wonder whether this also translated to differences in outcomes,” Hunter says. “And preliminary data suggests that it does.”

This disparity in choline levels prompted the researchers to look back at the results of the first clinical trial. When they did, they found that the gestational age at delivery in Black mothers who had been supplemented with choline was extended by an average of three weeks compared to Black mothers who didn’t receive supplementation.

“As an Ob/Gyn, preterm birth is one of the main adverse pregnancy outcomes that we're always working towards preventing,” Hoffman says. “And there are known disparities in both birth weight and risk of preterm birth between Black women and their children and almost every other group.”

Since preterm birth can have adverse effects on the development of cognition and behavior throughout childhood — including mental health — the results of the clinical trial and the subsequent observational study seem to point to two potential benefits of choline supplementation for pregnant women, and, in particular, Black women: enhanced prenatal development of inhibitory neuro-circuits in the brain and older gestational age at delivery.

How systemic racism in the U.S. may play a role in stress and pregnancy

Now the researchers were faced with the question of why Black mothers’ choline levels were so much lower than those of other women? They compared the choline levels of the Black pregnant women in the American study to blood samples from a cohort of pregnant women in Uganda and found that the choline levels of the Ugandan women were much higher than their American counterparts.

“Of course, we know that not all Black women in America are African American or of African heritage, Hunter says. “But still, it seemed like there was something else going on that might account for the racial differences we were seeing.”

So, they turned their attention to a potential culprit and differentiator: stress.

“Part of my contribution to the research group early on was looking at ways to capture and measure stress in relation to two primary pregnancy outcomes,” Hoffman says. “One was gestational age at birth and the other was birth weight, because both of those are markers for either long-term wellness or potential impairments.”

One of the group’s hypotheses was that the more stressed a mother is, the more her liver may sequester choline for itself, meaning that the fetus may not receive an adequate amount for neurodevelopment and is more at risk for preterm birth.

The team used Hoffman’s methods to collect measures of maternal stress in the observational study participants. And while the Black women didn't report feeling more stress, their hair cortisol levels, a biomarker of stress exposure, were higher than those of participants of other races.

“Even though they don't report it, their bodies looked more stressed,” Hunter says. “Our question now is whether there are stressors that Black women experience but that our questionnaires do not capture, or are cortisol levels reflecting accumulated exposure to low-level, background stressors, perhaps stemming from decades or lifetimes or even generations of institutional racism in this country. We don’t have the data to answer those questions yet, but we wanted to get this study out there to say, ‘this is something we should be paying attention to.’”

Could choline be the next folic acid?

The Food and Drug Administration (FDA) currently recommends that pregnant women get 550 milligrams of choline a day, but Hunter says that about 90% of pregnant women don't meet that goal.

“That's hard to do,” she says. “It's not that it can't be done, but it would be difficult. There have also studies that tried to raise choline levels in women by bringing them into a laboratory and providing them with high-choline foods, but they were not very successful.”

“The same was true for folic acid studies 20 years ago,” says Hoffman. “We recommend folic acid for pregnant women because it has a major impact on reducing neural tube defects. But the same story played out back in the early days of folic acid research, where the risk was significantly reduced when folate was included in a supplement versus trying to get people achieve adequate dietary intake. Dietary changes are hard to make, but we know you're going to get higher choline levels when you supplement.”

Hunter says the group hopes to do another clinical trial in the future where they supplement one cohort of Black women at the FDA-recommended choline level, plus another group at about two to three times the recommended amount to see if there is any additional benefit to supplementing at a higher level.

“If we're telling women that they need 550 milligrams of choline per day, but some other factor limits how much choline can get to the fetus, that level of intake may not adequately meet the needs of the developing fetus. We need to understand this,” she says.

Unfortunately, the supplements can be expensive: usually $600–$800 over the course of a pregnancy, and up to about $1,200 for some of the more expensive supplements.

Both Hoffman and Hunter hope to continue to raise awareness around this issue and the health disparity when it comes to Black women.

“For over 50 years, maternal fetal medicine has been trying to figure out ways that we can reduce preterm birth, and then we find a promising contender in the choline data set,” Hoffman says. “It's especially exciting because a major push in obstetrics right now is trying to close these known gaps in outcomes that exist for Black women and their children. The choline and cortisol connection gives us objective, physiologic measures to sort out what changes we need to make in terms of addressing health disparities”

Journal

Schizophrenia Bulletin

DOI

10.1093/schbul/sbab051

Credit: 
University of Colorado Anschutz Medical Campus

Study reveals how our immune system reacts to COVID-19 variants

image: The study included a cohort of plasma donors.

Image: 
Australian Red Cross Lifeblood

Australian scientists researching how our immune system responds to COVID-19 have revealed that those infected by early variants in 2020 produced sustained antibodies, however, these antibodies are not as effective against contemporary variants of the virus.

The research is one of the world's most comprehensive studies of the immune response against COVID-19 infection. It suggests vaccination is more effective than the body's natural immune response following infection and shows the need to invest in new vaccine designs to keep pace with emerging COVID variants.

Published today in PLOS Medicine, the study was made possible by a partnership between the University of Sydney, Kids Research, Sydney Children's Hospitals Network, the Kirby Institute at UNSW Sydney, Australian Red Cross Lifeblood, St Vincent's Hospital and NSW Health Pathology, as well as other local and international collaborators.

The team analysed the serum of 233 individuals diagnosed with COVID-19 over 7 months and uncovered that the level of immunity over time is dependent on disease severity and the viral variant. They show that antibodies developed during the first wave had reduced effectiveness against six variants, ranging from those observed in the second wave in Australia through to three variants of concern that have driven the global pandemic in the UK, Brazil and South Africa.

How do we study the immune response?

The serum of COVID-19 infected individuals was of interest as it is the part of our blood that contains crucial information about our immune system. Analysis of the serum made it possible to create a detailed timeline of the level of 'neutralising antibodies' produced against COVID-19 infection, and so to see if there was long-term immunity.

Neutralising antibodies are part of our immune system's frontline arsenal that is triggered during infection and vaccination. Their job is to shield cells that are usually the target of a pathogen (such as the SARS-CoV-2 virus which causes the COVID-19 disease) from being infected. The level of neutralising antibody response can be a defining feature of how effectively our body fights off illness.

Interestingly, a rare group of 'super responders' was also identified as an exception.

This group of 'super responders' had a stable and robust level of antibodies across all COVID-19 variants. The researchers say this group could prove useful for investigating the potential of convalescent plasma (using blood from people who have recovered to treat others) which has so far proven ineffective against severe COVID-19 illness. In addition, key donors could be looked at closely and their antibodies cloned for future therapeutic use.

Why it is important?

Co-senior author Associate Professor Fabienne Brilot of the University of Sydney and Kids Research, Sydney Children's Hospitals Network, and her research team led the analysis branch of the study, using highly sensitive tools they developed to study the antibodies in detail.

"We can learn a great deal from these people who were infected in the first wave in Australia as they were infected with the same variant that our current vaccines are based on," said Associate Professor Brilot.

"While the approved vaccines are showing good responses, our study highlights the importance of continued vaccine development, especially taking into account the differences in variants."

Co-senior author Associate Professor Stuart Turville of the Kirby Institute said the study was conducted to investigate the level, breadth and longevity of the immunity generated from COVID-19 infection and whether mutation of the virus compromises immunity.

"What this work has shown us is that current observations about vaccines show they offer a much broader protection against COVID-19 and its variants than the body's natural immune response following infection, which is usually only protective against the variant of the virus that the person was infected with. We, therefore, should not rely on the body's natural immune response to control this pandemic, but rather the broadly protective vaccines that are available."

Key findings

SARS-CoV-2 antibody responses are sustained for up to seven months post-infection.

The immune response remained stable in some individuals, and while it decreased in others, no individual showed a negative response during the seven-month period.

Levels of virus-neutralising antibodies were associated with COVID-19 severity.

Antibodies generated after early infection displayed a significantly reduced antibody binding and neutralisation potency to globally emerging viral variants.

Methods

The study analysed the serum from 233 individuals who were diagnosed with COVID-19 from February to October 2020. There were two cohorts to the study--a hospital-based cohort of patients (the ADAPT study at St Vincent's Hospital, Sydney) recruited during the first and second wave of infection in Australia and a national cohort of plasma donors (LIFEBLOOD).

10 COVID-19 strains and variants of concern/ interest were investigated, including:*

First known classified SARS-CoV-2 strain (Wuhan -1 D614)

Alpha (B.1.1.7, United Kingdom)

Beta (B.1.351, South Africa)

Gamma (P1, Brazilian)

Zeta (P2, Brazilian)

*Note naming conventions updated to reflect World Health Organisation classifications

The researchers used a comprehensive suite of assays that measured:

The longevity and type of antibody response against Spike from various variants over time in serum of COVID-19 diagnosed individuals.

Neutralisation of infectious SARS-CoV-2 over time, by infecting cell lines that had ACE2 on its surface (which SARS-CoV-2 binds and targets on the cell to begin infection) with a particle designed to mimic a version of the SARS-CoV-2 virus particle.

Credit: 
University of Sydney

New composites with magnetolectrical properties will help treat neurodegenerative diseases

Polymer composite materials that combine magnetic and electrical properties are the subjects of particular attention for modern-day researchers. Their basic property is the ability to convert electric polarization into a magnetic field and vice versa. Although some materials exhibit a much better magnetoelectric effect, polymer-based composites are easier not only to produce but also to modify.

Such composites have great potential in a variety of different fields. For example, using them as a basis, scientists can develop surfaces that help cultivate various cells. In this case, polymer composites serve as a substrate through which it is possible to affect the culture using a non-contact and controlled electric charge and morphological properties of the surface. It allows simulating natural conditions in the body. Due to such ample opportunities, researchers have been trying to improve the efficiency of the material for several years.

With the help of Russian and foreign colleagues, scientists from the I. Kant Baltic Federal University created two types of composites based on poly(vinylidene fluoride) (PVDF) polymers and a PVDF-based copolymer with the use of PVDF-TrFE trifluoroethylene.

Poly(vinylidene fluoride) is a multipurpose material with a wide array of applications. In a certain crystalline phase, it possesses piezoelectric properties that are expressed in the emergence of electrical polarization under the mechanical influence. Composites developed by the researchers demonstrate a change in polarization both under mechanical impact and the influence of a magnetic field due to the inclusion of magnetic nanoparticles in the polymer structure.

The researchers followed various approaches to modify nanocomposites in order to amplify and control the magnetoelectric response. They used a PVDF-based copolymer with extra pronounced piezoelectric properties, then tried additives from piezoelectric and magnetic particles. The results of the experiments show that the addition of particles of barium titanate (BaTiO3) with a concentration of 5-10% can significantly enhance the magneto-electric effect.

"We have also shown that our composites are biocompatible, that is, they do not harm living systems. This was confirmed in our experiment with the embryonic stem cells of mice. This type of cell is very sensitive to the conditions of cultivation, including the properties of the substrate. Further research will be aimed at increasing the magnetoelectric effect. This is possible due to changes in the size, shape, and concentration of particles in such composites", Kateryna Levada comments, Ph.D., the Head of the Biomedical Applications Laboratory of the REC "Smart Materials and Biomedical Applications".

Credit: 
Immanuel Kant Baltic Federal University

Aging-related conditions increase treatment burden in older cancer patients

DANVILLE, Pa. - Having multiple chronic health conditions and living in a rural area were the top two factors affecting increased healthcare system contact among older patients with bladder cancer, a research team has found.

The Geisinger-led team evaluated 73,395 Medicare beneficiaries age 66 and older who had been diagnosed with non-muscle-invasive bladder cancer to assess their treatment burden, defined as the number of days the patients had contact with a health system in the year following diagnosis.

Nearly two-thirds of the patients had multiple co-existing chronic conditions at the time of bladder cancer diagnosis, as well as other aging-related conditions, including a history of falls, cognitive impairment, depression, weight loss or urinary incontinence. The mean treatment burden for the group was 8.9 days.

The research team found that the presence of multiple co-existing conditions had the largest effect on treatment burden, with each additional condition increasing the average number of health system contact days by 13%. Regardless of the number of chronic conditions reported, rural patients consistently had higher treatment burden than their urban counterparts.

The results were published in the Journal of Geriatric Oncology.

"These findings highlight the need for interventions that reduce treatment burden among the growing population of older adults with cancer, particularly in rural areas," said Tullika Garg, M.D., M.P.H., a urologic oncologist at Geisinger and lead author of the study. "Cancer care, and care for other chronic conditions, goes beyond a single-disease approach and needs to account for the whole person."

Geisinger is making better health easier for patients age 65 and older and those with chronic conditions through innovative programs like 65 Forward Health Centers, offering personalized primary care and wellness services for Geisinger Gold members, and Geisinger at Home, bringing care into the home for Geisinger Gold members with certain chronic conditions.

Credit: 
Geisinger Health System

Identified an early neuronal dysfunction in Parkinson's that could help early diagnosis

image: Schematic of the experimental design for investigating the emergence of functional alterations in dopaminergic neurons obtained from PD patient-specific iPSC. After their generation in the plate, monitorisation of calcium intracellular levels has been used to follow the organisational changes and dynamical traits of the neuronal networks during maturation. Functional analysis of the neuronal connectivity in these cultures allowed the study of early events that originate the pathology. Gene editing in the original patient derived iPSC allowed to revert these defects.

Image: 
G. Carola et al.

Researchers from IDIBELL and the University of Barcelona (UB) have described that neurons derived from Parkinson's patients show impairments in their transmission before neurodegeneration.
For this study, it has been used dopaminergic neurons differentiated from patient stem cells as a model.

Parkinson's is a neurodegenerative disease characterized by the death of dopaminergic neurons. This neuronal death leads to a series of motor manifestations characteristic of the disease, such as tremors, rigidity, slowness of movement, or postural instability. In most cases, the cause of the disease is unknown, however, mutations in the LRRK2 gene are responsible for 5% of cases.

Current therapies against Parkinson's are focus on alleviating the symptoms but do not stop its progression. It is thought that early interventions before the appearance of the first symptoms that prevent neuronal death could slow down or even stop the evolution of the disease. However, currently, the diagnosis is based on the appearance of symptoms, when 70% of the neurons have already been lost.

A group of researchers from IDIBELL and the University of Barcelona (UB), led by Dr. Antonella Consiglio (group leader at IDIBELL, ICREA Academy researcher, and professor at the Faculty of Medicine and Health Sciences of the UB and IBUB/Institute of Biomedicine of the UB), Dr. Angel Raya (coordinator of the IDIBELL Regenerative Medicine program and ICREA researcher) and Dr. Jordi Soriano (group leader and professor at the UB and the Institute of Complex Systems from the University of Barcelona), with other national and international collaborators, have identified early functional deficiencies, before death, in neurons derived from patients with genetic Parkinson's. According to Dr. Consiglio ", these discoveries open the door to early diagnosis, which would allow us to carry out a premature intervention that would slow down neuronal death, and therefore, would stop the evolution of the disease".

In this work, dopaminergic neurons, the most vulnerable in Parkinson's, differentiated from stem cells (iPSC) of healthy individuals and patients with genetic Parkinson's, have been used as a model. Researchers have observed that these dopaminergic neurons are capable of maturing and forming functional neural networks in culture, in both control and Parkinson's disease conditions.

However, in this work published in npj Parkinson's Disease, it is shown that neurons from individuals with Parkinson's are more spontaneously active and present more explosion episodes in which, for example, the entire network is activated at the same time. All this before the neurodegeneration. The researchers believe that this early neuronal dysfunction could be contributing to initiating the cascade of events responsible for the death of dopaminergic neurons, and consequently, Parkinson's disease. Furthermore, this work highlights the extraordinary window of opportunity provided by experimental models based on iPSC in the understanding and presymptomatic evaluation of neurodegenerative diseases.

This work was supported by the European Research Council-ERC, the Spanish Ministry of Economy and Competitiveness, the Carlos III Institute, AGAUR, and the CERCA program of the Generalitat de Catalunya.

Credit: 
University of Barcelona

A universal approach to tailoring soft robots

video: Soft robot with optimised swimming properties

Image: 
SUTD

By combining two distinct approaches into an integrated workflow, Singapore University of Technology and Design (SUTD) researchers have developed a novel automated process for designing and fabricating customised soft robots. Their method, published in Advanced Materials Technologies, can be applied to other kinds of soft robots--allowing their mechanical properties to be tailored in an accessible manner.

Though robots are often depicted as stiff, metallic structures, an emerging class of pliable machines known as soft robots is rapidly gaining traction. Inspired by the flexible forms of living organisms, soft robots have wide applications in sensing, movement, object grasping and manipulation, among others. Yet, such robots are still mostly fabricated through manual casting techniques--limiting the complexity and geometries that can be achieved.

"Most fabrication approaches are predominantly manual due to a lack of standard tools," said SUTD Assistant Professor Pablo Valdivia y Alvarado, who led the study. "But 3D printing or additive manufacturing is slowly coming into play as it facilitates repeatability and allows more complex designs--improving quality and performance."

According to Dr Valdivia y Alvarado, embedded 3D printing--wherein various material inks are extruded in a supportive matrix--is especially suited for fabricating soft robots made of multiple materials or composites. However, to ensure that these robots are optimally designed, the team turned to topology optimisation (TO), where mathematical models are employed to design bespoke structures within a set of constraints.

By automating these two key steps in a single framework, the authors hoped to develop an integrated workflow for creating customised soft robots and minimise potential errors along the way. For the study, the group used a swimming autonomous robot inspired by batoids. The workflow starts by defining the robot's fin geometry, after which TO is used to generate the desired structure with desired properties within prescribed material and motion constraints. The optimised design is then transformed into a code that is read by the team's custom-built 3D printers, which in turn fabricate the robot.

The batoid-inspired soft robots were designed to survive the marine environment's harsh conditions and the approach focused on tailoring their fin composition and assessing how these changes could impact the fabricated robot's swimming performance.

Specifically, three types of fins were created--with two fins respectively made of soft and stiff materials as well as a third fin designed through TO combining the two materials. Unlike the first two fins, which were fabricated using traditional methods, the third composite fin was made following the integrated workflow.

Incredibly, the soft robot with the optimised composite fins was 50 per cent faster than its counterpart with the traditionally casted soft fin, with a speed slightly higher than the robot with the hard fin. The same prototype with the composite fin also turned roughly 30 per cent faster compared to the soft fin and had the smallest turning radius among the three robots--making it better at maneuvering through water.

Having successfully demonstrated the effectiveness of their approach, Dr Valdivia y Alvarado noted that their workflow for fabricating optimised, multi-material soft robots can be universally applied to design other soft robots.

"For example, if we're building a sensor, our objective in TO could be to tailor the electrical conductivity of certain portions of the structure," said Dr Valdivia y Alvarado. "Customising optical, thermal, electrical, as well as other physico-chemical properties would also be interesting for other applications."

Credit: 
Singapore University of Technology and Design

Wolbachia and the paradox of growth regulation

image: Forward genetics in Wolbachia: Regulation of Wolbachia proliferation by the amplification and deletion of an addictive genomic island

Image: 
IGC 2021

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.

Credit: 
Instituto Gulbenkian de Ciencia

Mucus and mucins may become the medicine of the future

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.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

For female vampire bats, an equal chance to rule the roost

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."

Credit: 
Ohio State University

Slow music in tunnels can keep drivers focused and safe

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."

Credit: 
Frontiers

Wild birds learn to avoid distasteful prey by watching others

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.

Credit: 
University of Helsinki

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

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."

Credit: 
York University

Public diplomacy by a visiting national leader sways public opinion in host country

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.

Credit: 
Dartmouth College

Mapping dengue hot spots pinpoints risk for Zika and chikungunya

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. 

Credit: 
Emory Health Sciences