Patients with acute heart attacks (ST elevation myocardial infarction, or STEMI) are very likely to survive if they undergo timely reopening of the occluded coronary artery (coronary reperfusion) in specialized clinical centers. Despite the given survival rates and major improvements in treatment, progression to heart failure still represents a major clinical problem. The patients’ longer-term outcomes depend on the extent of the damage to their heart tissue.

Lead investigator Helen M. Arthur, PhD, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, explains: “Coronary reperfusion after STEMI is standard therapy to salvage ischemic heart muscle. However, evidence suggests that the subsequent inflammatory response that the body initiates to repair the damaged heart tissue can also cause further loss of viable heart muscle. The more muscle that is lost, the greater the risk of subsequent progression to heart failure. The reason for this study was to investigate the potential protective effects of TGFβ1as a possible intervention to minimize this additional damage to the heart beyond the ischemic damage caused by the heart attack itself.”

The research team found that levels of an important anti-inflammatory protein TGFβ1 in the blood of STEMI patients 24 hours after reperfusion correlated with a reduction in infarct size after three months. To investigate this further they used an established mouse model of a heart attack to test the protective effects of TGFβ1, a protein known to be released in the body in response to tissue injury. They also studied its mimic HpTGM, a protein produced by a parasitic worm to help evade the immune response and thereby enable the worm to live within the tissue lining the gut. Intravascular delivery of either of these naturally occurring anti-inflammatory proteins reduced the injurious inflammatory response within the heart and importantly, the extent of heart injury as evidenced by reduced mature scar size.

The investigators were surprised to find almost identical beneficial effects of TGFβ1 and HpTGM treatment. Although TGFβ1 and HpTGM are evolutionarily unrelated, both these molecules interact with cells in a similar manner by activating the same signalling pathway. The dose of anti-inflammatory therapy was given at the time of reperfusion, which corresponds to a clinically useful time for a therapeutic intervention in humans.

Investigators could attribute the beneficial outcomes to the protective effect of these molecules on endothelial cells — the cells lining the blood vessels that help to regulate the exit of proinflammatory white blood cells from the circulation and enter the injured tissue. TGFβ1 has well-established anti-inflammatory properties, whereas HpTGM is a parasitomimetic with great clinical potential. Recent work in the Maizels laboratory at the University of Glasgow has also shown that delivery of HpTGM has a major anti-inflammatory effect in mouse models of colitis or airway inflammation, taking advantage of the product evolved by a parasite to quell the immune response to its presence.

Dr. Arthur concluded: “The current study shows that exogenous delivery of HpTGM at the time of coronary artery reperfusion dampens the proinflammatory response of coronary endothelial cells and reduces cardiac injury, leading to increased myocardial salvage and reduced scar size with the corollary of improved prospects for long-term cardiac function. The use of HpTGM as an anti-inflammatory therapy in treating heart attack patients is clearly an exciting prospect that requires further translational studies.”

Most current asthma treatments stem from the idea that it is an inflammatory disease. Yet, the life-threatening feature of asthma is the attack or the constriction of airways, making breathing difficult. The new study, published today in Science, shows for the first time that many features of an asthma attack — inflammation, mucus secretion, and damage to the airway barrier that prevents infections — result from this mechanical constriction in a mouse model.

The findings suggest that blocking a process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.

Professor Jody Rosenblatt from King’s College London said: “Our discovery is the culmination of more than ten years work. As cell biologists who watch processes, we could see that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma sufferers are far more likely to get long-term inflammation, wound healing, and infections that cause more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all these events.”

In the UK, 5.4 million people have asthma and can suffer from symptoms such as wheezing, coughing, feeling breathlessness and a tight chest. Triggers such as pollen or dust can make asthma symptoms worse and can lead to a life-threatening asthma attack.

Despite the disease commonality, the causes of asthma are still not understood. Current medications treat the consequences of an asthma attack by opening the airways, calming inflammation, and breaking up the sticky mucus which clogs the airway, which help control asthma, but do not prevent it.

The answer to stopping asthma symptoms may lie in cell extrusion, a process the researchers discovered that drives most epithelial cell death. Scientists used mouse lung models and human airway tissue to discover that when the airways contract, known as bronchoconstriction, the epithelial cells that line the airway get squeezed out to later die.

Because bronchoconstriction causes so many cell extrusions, it damages the airway barrier which causes inflammation and excess mucus.

In previous studies, the scientists found that the chemical compound gadolinium can block extrusion. In this study, they found it could work in mice to prevent the excess extrusion that causes damage and inflammation after an asthma attack. The authors note that gadolinium has not been tested in humans and has not been deemed to be safe or efficacious.

Professor Rosenblatt said: “This constriction and destruction of the airways causes the post-attack inflammation and excess mucus secretion that makes it difficult for people with asthma to breathe.

“Current therapies do not prevent this destruction — an inhaler such as Albuterol opens the airways, which is critical to breathing but, dishearteningly, we found it does not prevent the damage and the symptoms that follow an attack. Fortunately, we found that we can use an inexpensive compound, gadolinium which is frequently used for MRI imaging, to stop the airway damage in mice models as well as the ensuing inflammation and mucus secretion. Preventing this damage could then prevent the build-up of musculature that cause future attacks.”

Professor Chris Brightling from the University of Leicester and one of the co-authors of the study said: “In the last decade there has been tremendous progress in therapies for asthma particularly directed towards airway inflammation. However, there remains ongoing symptoms and attacks in many people with asthma. This study identifies a new process known as epithelial extrusion whereby damage to the lining of the airway occurs as a consequence of mechanical constriction and can drive many of the key features of asthma. Better understanding of this process is likely to lead to new therapies for asthma.”

Dr Samantha Walker, Director of Research and Innovation at Asthma + Lung UK, said: “Only two per cent of public health funding is allocated to developing new treatments for the 12 million people living with lung conditions in the UK so new research that can help in the treatment or prevention of asthma is good news.

“This research using an experimental mouse model shows that constricting the airways leads to damage to the lung lining and inflammation, like that seen in asthma. It is this constriction and resulting damage that makes it difficult for people with asthma to breathe.

“Current medications for asthma work by treating the inflammation, but this isn’t effective for everyone. Treatments aim to prevent future asthma attacks and improve asthma control by taking inhalers every day, but we know that ~31 per cent of people with asthma don’t have treatment options that work for them, putting them at risk of potentially life-threatening asthma attacks.

“This discovery opens important new doors to explore possible new treatment options desperately needed for people with asthma rather than focusing solely on inflammation.”

The discovery of the mechanics behind cell extrusion could underlie other inflammatory diseases that also feature constriction such as cramping of the gut and inflammatory bowel disease.

The paper is in collaboration with the University of Leicester and funded by Wellcome, Howard Hughes Medical Institute and the American Asthma Foundation.

“Society is facing a slew of global challenges, and we wanted to assess the extent to which higher education is contributing to the sort of transformative change needed to address these challenges,” says Christopher Galik, co-author of the study and a professor of public administration at North Carolina State University. “For this study, we started at the local level, exploring whether there was any association between university sustainability performance and sustainability in their surrounding communities.”

To explore the issue, researchers looked at data from 105 metropolitan areas in the United States, which are collectively home to 427 higher education institutions. Specifically, the researchers drew on data from two sources, the U.S. Cities Sustainable Development Goal (SDG) Index and the QS Sustainability Universities Ranking.

The SDG Index aggregates dozens of metrics related to a municipality’s sustainability efforts, covering issues such as climate action, energy efficiency and water use. The QS Sustainability Universities Ranking evaluates university efforts related to environmental sustainability as well as efforts aimed at addressing social concerns, such as global partnerships, community engagement and the health and well-being of students, faculty and staff.

The researchers wanted to see whether there was any relationship between universities that scored well on the QS Sustainability Universities Ranking and the municipalities that scored well on the SDGs.

“Sustainability is complicated — it has lots of different components,” says Ha Vien, first author of the paper and a Ph.D. student at North Carolina State University. “And we found that universities are associated with progress on some of those measures, but not others.”

The good news is that there was a very strong correlation between universities that score well on sustainability and communities that score well on innovation, reducing poverty, creating economic opportunities and reducing inequality.

“The bad news is that universities that perform strongly on sustainability measures are also associated with a decline in responsible consumption and production — measured here as increased air pollution and release of toxic chemicals — in their surrounding areas,” Vien says. “There was also little or no correlation between universities that scored well on environmental sustainability and the environmental sustainability scores of their communities.”

“This is an observational study, so it’s impossible to determine causation,” Galik says. “However, the evidence suggests two things. First, universities continue to be strongly associated with innovation and economic development. But second, the idea that universities can contribute to broader sustainable transformations doesn’t seem to be realized yet, at least on a large scale.”

“It took significant time and effort for universities to become the economic drivers that we see today,” Vien says. “Looking into the future, climate change will continue to be a defining challenge for the foreseeable future. Our findings highlight that there are still a lot of opportunities for higher education to make more of a difference in surrounding communities.”

The first-of-its-kind metafluid uses a suspension of small, elastomer spheres — between 50 to 500 microns — that buckle under pressure, radically changing the characteristics of the fluid. The metafluid could be used in everything from hydraulic actuators to program robots, to intelligent shock absorbers that can dissipate energy depending on the intensity of the impact, to optical devices that can transition from clear to opaque.

The research is published in Nature.

“We are just scratching the surface of what is possible with this new class of fluid,” said Adel Djellouli, a Research Associate in Materials Science and Mechanical Engineering at SEAS and first author of the paper. “With this one platform, you could do so many different things in so many different fields.”

Metamaterials — artificially engineered materials whose properties are determined by their structure rather than composition — have been widely used in a range of applications for years. But most of the materials — such as the metalenses pioneered in the lab of Federico Capasso, Robert L. Wallace Professor of Applied Physics and Vinton Hayes Senior Research Fellow in Electrical Engineering at SEAS — are solid.

“Unlike solid metamaterials, metafluids have the unique ability to flow and adapt to the shape of their container,” said Katia Bertoldi, William and Ami Kuan Danoff Professor of Applied Mechanics at SEAS and senior author of the paper. “Our goal was to create a metafluid that not only possesses these remarkable attributes but also provides a platform for programmable viscosity, compressibility and optical properties.”

Using a highly scalable fabrication technique developed in the lab of David A. Weitz, Mallinckrodt Professor of Physics and of Applied Physics at SEAS, the research team produced hundreds of thousands of these highly-deformable spherical capsules filled with air and suspended them in silicon oil. When the pressure inside the liquid increases, the capsules collapse, forming a lens-like half sphere. When that pressure is removed, the capsules pop back into their spherical shape.

That transition changes many of the liquid’s properties, including its viscosity and opacity. Those properties can be tuned by changing the number, thickness and size of the capsules in the liquid.

The researchers demonstrated the programmability of the liquid by loading the metafluid into a hydraulic robotic gripper and having the gripper pick up a glass bottle, an egg and a blueberry. In a traditional hydraulic system powered by simple air or water, the robot would need some kind of sensing or external control to be able to adjust its grip and pick up all three objects without crushing them.

But with the metafluid, no sensing is needed. The liquid itself responds to different pressures, changing its compliance to adjust the force of the gripper to be able to pick up a heavy bottle, a delicate egg and a small blueberry, with no additional programming.

“We show that we can use this fluid to endow intelligence into a simple robot,” said Djellouli.

The team also demonstrated a fluidic logic gate that can be reprogrammed by changing the metafluid.

The metafluid also changes its optical properties when exposed to changing pressures.

When the capsules are round, they scatter light, making the liquid opaque, much like air bubbles make aerated water appear white. But when pressure is applied and the capsules collapse, they act like microlenses, focusing light and making the liquid transparent. These optical properties could be used for a range of applications, such as e-inks that change color based on pressure.

The researchers also showed that when the capsules are spherical, the metafluid behaves like a Newtonian fluid, meaning its viscosity only changes in response to temperature. However, when the capsules are collapsed, the suspension transforms into a non-Newtonian fluid, meaning that its viscosity will change in response to shear force — the greater the shear force, the more fluid it becomes. This is the first metafluid that has been shown to transition between Newtonian and non-Newtonian states.

Next, the researchers aim to explore the acoustic and thermodynamic properties of the metafluid.

“The application space for these scalable, easy-to-produce metafluids is huge,” said Bertoldi.

Harvard’s Office of Technology Development has protected the intellectual property associated with this research and is exploring commercialization opportunities.

The research was supported in part by the NSF through the Harvard University Materials Research Science and Engineering Center grant number DMR-2011754.

It was co-authored by Bert Van Raemdonck, Yang Wang, Yi Yang, Anthony Caillaud, David Weitz, Shmuel Rubinstein and Benjamin Gorissen.

In 2019, six people died from a listeria outbreak caused by contaminated ready-to-eat foods served in a number of hospitals across the UK. In light of this, scientists are now performing vital research which helps to understand how these pathogens can persist in ready-to-eat food preparation environments.

Listeria monocytogenes is a foodborne bacterium that causes an illness called listeriosis. Symptoms for healthy individuals include a high temperature, aches and pains, feeling or being sick; but infection in those who are pregnant, elderly or immunocompromised, can lead to death.

The safety of foods is therefore paramount within the food industry. However, even in the face of well-implemented strategies to disinfect facilities and control for microbial risks, microbes such as listeria can occasionally breach food safety barriers and cross-contaminate food products. This is particularly dangerous in ready-to-eat foods where consumers will not kill contaminating bacteria by heating the food before eating it. Despite this danger, very little research has been done to understand the bacteria in ready-to-eat food production environments.

Researchers wanted to understand the potential sources of cross contamination and the factors that contribute to the survival of L. monocytogenes in these environments,particularly the communities of other microbes that support and protect it.

They began by sampling the floor of a ready-to-eat food factory that had recurrently detected L. monocytogenes in specific non-food contact areas of the factory. They sampled different sites: a preparation area, where ingredients were kept at 4°C, and a production area where they assembled and packaged the food, kept at 10°C. They aimed to measure the changes of bacterial communities over time, so they sampled the sites over ten weeks, before and after cleaning. They then cultured and performed genetic analysis on the samples to identify which bacteria were present and in what proportions.

The results showed that the populations of bacteria that coexist with L. monocytogenes were stable over time and have adapted to the conditions on the factory floor, including food safety controls. Maria Diaz from the Quadram Institute and lead of the study explains, “as L. monocytogenes is supported by a stable community of other bacteria, we may now need to develop new strategies to alter the whole bacterial population to effectively eliminate the pathogen.”

While the overall bacterial populations, and proportions of bacteria were stable before and after cleaning, Maria explains that we cannot assume cleaning efforts do not work. “The populations are very stable, and cleaning is not shifting the composition — it’s not letting one bacterium grow over another. After cleaning, the bacteria reduce in numbers and the bacterial load is lower, making cross contamination less likely.”

There was a marked difference, however, between the different areas of the factory at different temperatures; suggesting that the bacterial populations are highly adapted to the different environments within the factory. It also suggests that the bacteria present in the factory are established populations rather than bacteria introduced from outside sources — as despite movement of personnel between them, the populations remained stable.

While the factory had listeria under control at the time of sampling, this new research is important for understanding the different communities of microbes in different environments across ready-to eat-food facilities. Researchers hope that understanding how listeria survives in these environments could inform more accurate laboratory testing of cleaning methods. Maria adds, “thanks to this research, we can better understand the lifestyle of this pathogen and start to develop laboratory models that allow us to investigate new ways of killing listeria.”

Maria Diaz will present her data at this year’s Microbiology Society Annual Conference which will take place at Edinburgh International Convention Centre. Her talk “Deciphering microbial dynamics in a Ready-to-Eat Food production facility: Insights into Listeria monocytogenes persistence” will take place on 11 April.