Culture

NEW YORK, NY (June 9, 2020) -- A new study of lung anatomy may explain why 1 in 4 cases of COPD--a lung disease most often linked to smoking--occur in people who have never smoked, a fact that has long perplexed researchers.

The research analyzed CT scans of more than 6,500 adults and found that people with small airways relative to their lungs' volume--a relationship termed dysanapsis--are at increased risk of chronic obstructive pulmonary disease (COPD) regardless of their smoking habits.

"Our study shows that having an undersized airway tree compromises breathing and leaves you vulnerable to COPD later in life," says lead author Benjamin M. Smith, MD, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.

"Our findings suggest that dysanapsis is a major COPD risk factor -- on par with cigarette smoking," Smith says. "Dysanapsis is believed to arise early in life. Understanding the biological basis of dysanapsis may one day lead to early life interventions to promote healthy and resilient lung development."

The study was published online today in the Journal of the American Medical Association.

What Is Dysanapsis

Air is transported into the lung via airways that resemble the branches of a tree.

In the 1970s, researchers using simple lung function tests speculated that some people have undersized airways relative to the volume of their lungs. The size mismatch was termed dysanapsis and is believed to develop in childhood when airway branches grow more slowly than lung volume. With the advent of high-resolution in vivo imaging, dysanapsis could finally be measured directly in large cohorts.

Dysanapsis and Health

For many decades, the clinical significance of dysanapsis was unclear due to the difficulty in measuring airway and lung dimensions in large samples of smokers and nonsmokers.

A recent study showed that half of older adults with COPD had low lung function early in life.

"This observation motivated us to think about early life origins of COPD," Smith says. "Combining classic theories from respiratory physiology with state-of-the-art imaging in large epidemiological samples, we tested whether dysanapsis might explain a significant proportion of COPD risk."

COPD--including emphysema and chronic bronchitis-- is characterized by reduced airflow from the lungs and is the third-leading cause of death in the United States.

Lung anatomy Linked to COPD

In the new study, Smith and his colleagues analyzed health data, including lung CT scans, from more than 6,500 older adults enrolled in three major lung studies in the United States and Canada.

They found that individuals with smaller airways relative to lung size had the poorest lung function and the highest risk of COPD and were 8 times more likely to develop COPD.

The findings support a landmark 2015 study demonstrating two major pathways that lead to COPD later in life. In the classic paradigm, individuals with normal lung function experience a rapid decline after years of exposure to irritants, like cigarette smoke or air pollution.

"But there's a second pathway in people who have reduced lung function from an early age. This low starting point increases the risk for COPD in later years, even in the absence of rapid lung function decline," says Smith. "Based on our data, dysanapsis may account for a large percentage of these cases."

Dysanapsis and Smoking

The association between dysanapsis and COPD risk existed for both smokers and nonsmokers and may also explain why only a minority of heavy smokers develop COPD.

The study also looked at the lifelong heavy smokers without COPD and found that these participants had larger than expected airways for their lung size.

"This suggests that people at the opposite end of the dysanapsis spectrum, i.e. those with larger than expected airways, may be able to incur considerable damage from smoking while maintaining enough reserve to avoid COPD," says Smith. "Of course, the harmful effects of smoking are legion, including lung cancer, heart disease, and stroke. So anyone who smokes should do their best to quit."

In times of unexpected uncertainty, such as the sudden appearance of a global pandemic, people may be more prone to paranoia, Yale University researchers suggest in a new study published in the journal eLife.

"When our world changes unexpectedly, we want to blame that volatility on somebody, to make sense of it, and perhaps neutralize it,'' said Yale's Philip Corlett, associate professor of psychiatry and senior author of the study. "Historically in times of upheaval, such as the great fire of ancient Rome in 64 C.E. or the 9/11 terrorist attacks, paranoia and conspiratorial thinking increased."

Paranoia is a key symptom of serious mental illness, marked by the belief that other people have malicious intentions. But it also manifests in varying degrees in the general population. For instance, one previous survey found that 20% of the population believed people were against them at some time during the past year; 8% believed that others were actively out to harm them.

The prevailing theory is that paranoia stems from an inability to accurately assess social threats. But Corlett and lead author Erin Reed of Yale hypothesized that paranoia is instead rooted in a more basic learning mechanism that is triggered by uncertainty, even in the absence of social threat.

"We think of the brain as a prediction machine; unexpected change, whether social or not, may constitute a type of threat -- it limits the brain's ability to make predictions," Reed said. "Paranoia may be a response to uncertainty in general, and social interactions can be particularly complex and difficult to predict."

In a series of experiments, they asked subjects with different degrees of paranoia to play a card game in which the best choices for success were changed secretly. People with little or no paranoia were slow to assume that the best choice had changed. However, those with paranoia expected even more volatility in the game. They changed their choices capriciously -- even after a win. The researchers then increased the levels of uncertainty by changing the chances of winning halfway through the game without telling the participants. This sudden change made even the low-paranoia participants behave like those with paranoia, learning less from the consequences of their choices.

In a related experiment, Yale collaborators Jane Taylor and Stephanie Groman trained rats, a relatively asocial species, to complete a similar task where best choices of success changed. Rats who were administered methamphetamine -- known to induce paranoia in humans -- behaved just like paranoid humans. They, too, anticipated high volatility and relied more on their expectations than learning from the task.

Reed, Corlett and their team then used a mathematical model to compare choices made by rats and humans while performing these similar tasks. The results from the rats that received methamphetamine resembled those of humans with paranoia, researchers found.

"Our hope is that this work will facilitate a mechanistic explanation of paranoia, a first step in the development of new treatments that target those underlying mechanisms," Corlett said.

"The benefit of seeing paranoia through a non-social lens is that we can study these mechanisms in simpler systems, without needing to recapitulate the richness of human social interaction," Reed said.

The way we measure economic health is flawed, according to new research from the Stanford-based Natural Capital Project. When we talk about a country's economic prosperity, we're almost always referring to gross domestic product, or GDP, a calculated value based on the goods and services that flow through an economy. But GDP doesn't account for many of the benefits that people and economies receive from nature, like clean water and climate security.

To address this economic gap, Stanford researchers developed a new metric for measuring the value of nature's contributions to economic activity. Their study, published in Proceedings of the National Academy of Sciences, details how the approach, known as Gross Ecosystem Product (GEP) is being successfully implemented in China.

"We're basically flying blind when it comes to knowing where and how much nature to protect," said the study's senior author Gretchen Daily, a professor of environmental science at Stanford's School of Humanities and Sciences.

"GEP tracks the vital contributions of nature to society, informs investments in securing them and helps evaluate the performance of leaders and policies," added Daily, who is also the faculty director of the Natural Capital Project, an interdisciplinary partnership that helps governments and organizations integrate the values of nature's contributions into economic and development plans.

The researchers used InVEST, the Natural Capital Project's open-source mapping and modeling software, to calculate the flow of benefits that nature provides to people and inform the GEP equation. GEP is calculated in parallel ways to GDP, accounting for and aggregating all of nature's contributions to people in a single, monetary metric. These contributions provide a new lens with which to assess income and performance.

"Over the past 50 years, global GDP has risen by 370 percent," said co-author Stephen Polasky, professor of ecological and environmental economics at the University of Minnesota. "Alongside global economic prosperity, we're seeing the degradation of the vital natural capital that fundamentally underpins human well-being."

The Chinese Academy of Sciences has pioneered the concept of GEP and compiled a wealth of environmental data to do the calculations. Led by Zhiyun Ouyang, director of the academy's Research Center for Eco-Environmental Sciences and lead author on the study, the research team used Qinghai province in China as a testing ground for the new measure. Qinghai province is known as the "water tower of Asia" because it sits at the source of the Mekong, Yangtze and Yellow rivers, which provide water to much of China and other Southeast Asian countries.

"Qinghai is rich in natural capital, but its GDP alone does not reflect that value," Ouyang said. "Using this new metric, we were able to place a value on important ecosystem services, especially water supply, that Qinghai currently exports to other provinces but receives no credit for in the GDP calculation."

The people downstream who benefit from Qinghai's water supply tend to live in provinces wealthier in GDP and, in urban areas, often poorer in GEP. Using GEP, leaders in China are informing "eco-compensation" programs that enable downstream water users to pay for the protection of the water source upstream. These types of programs can help alleviate poverty while keeping critical ecosystem benefits flowing.

The researchers are also thinking about how the new measure could be linked to policy. "GEP by itself is just a metric, a number. But when used to inform and drive policies, it can be a powerful new tool for changing the ways we understand and value nature globally," said Mary Ruckelshaus, managing director of the Natural Capital Project. "Being held accountable for reporting GEP may incentivize governments to make decisions that protect the natural resources on which we all depend."

Like the payment for the water eco-compensation program in China, other countries and governments have been implementing schemes to allow payment for the provision and protection of ecosystem services for decades. But policy development can be slow and burdensome, especially without a standardized measurement or approach. GEP will enable governments to more easily compare options and weigh tradeoffs between different conservation decisions.

The ultimate goal is to see the successes of its application in China applied globally so that economies everywhere track and secure the values of nature to society. The researchers are working with the United Nations Statistics Division to develop ways to scale and standardize GEP as a global reporting metric.

"We see a potential future where GEP is reported alongside GDP in all economies," said Daily. "The use of GEP yielding tangible results already - creating jobs and restoring critical ecosystems. Securing natural capital is at the heart of a future in which all of us can thrive."

OAK BROOK, Ill. - A minimally invasive procedure that destroys cancer cells by freezing them is as effective as surgery for treating early-stage kidney cancer, offering similar 10-year survival rates with a lower rate of complications, according to a study published in the journal Radiology.

Kidney cancer is among the 10 most common cancers in men and women in the United States. About 70% of cases are found at stage 1, the earliest stage. Treatment typically involves surgical removal of the tumor from the kidney, also known as a partial nephrectomy. Radical nephrectomy, or removal of the entire kidney, is another surgical option.

Percutaneous cryoablation (PCA) has emerged as an alternative to surgery that kills the tumor by freezing it. In the procedure, an interventional radiologist inserts a hollow needle into the tumor under imaging guidance. Argon gas circulating through the needle freezes a small volume of tissue, including the tumor and a small amount of normal tissue around it. The tumor dies, and over time it turns into scar tissue that is absorbed by the body.

"We have been doing cryoablation with increasing frequency at Johns Hopkins," said study lead author Christos S. Georgiades, M.D., Ph.D., professor of radiology, oncology and surgery from the Department of Vascular and Interventional Radiology at Johns Hopkins University in Baltimore. "It's an outpatient procedure that takes about 30 to 40 minutes to perform. We observe the patient for three hours, and then they can go home."

For the study, Dr. Georgiades and colleagues looked at 134 patients who underwent cryoablation for early-stage kidney cancer and compared their outcomes over 10 years with those of patients who had either a radical or partial nephrectomy.

Disease-specific survival--that is, the proportion of patients who were still alive or had died from some other cause besides kidney cancer--was 94% at both five and 10 years after treatment, a figure comparable to that reported after radical or partial nephrectomy. Overall survival probability after percutaneous cryoablation at five and 10 years was longer than for radical or partial nephrectomy.?

"For certain patients, cryoablation is equivalent to surgery with fewer side effects," Dr. Georgiades said. "The risk of significant complications from this procedure is about 6%, compared to between 15 and 20% for surgery. In addition, recovery is much faster than with surgery."

The study also found that cryoablation was associated with a low 10-year risk of hemodialysis.

Dr. Georgiades emphasized that cryoablation is only appropriate for early-stage kidney cancer that is confined to the kidney and is up to about 4 centimeters in size. It would not be effective in larger tumors. He doesn't treat patients with cryoablation unless they see a urologist first to get briefed on the surgical option.

"If a patient is interested in hearing about cryoablation, I'll explain the risks, benefits and outcomes," Dr. Georgiades said. "At Johns Hopkins, we give patients all the options and, in the end, they make the final decision. I only offer cryoablation if I know it's going to be beneficial to the patient."

As of now, the standard of care for early-stage kidney cancer is partial nephrectomy. However, the study results from Johns Hopkins, along with results from other studies, are likely to be considered by medical societies as they update their guidelines.

"Studies like this may convince societies to make cryoablation the go-to option, at least for early-stage kidney cancer," Dr. Georgiades said.

An international study that has been carried out on nearly 3000 people in Norway, Germany, and Iceland, shows that our kidney function deteriorates with age, even if we do not have any other diseases. The results from the study have recently been published in the reputable journal for kidney diseases, Journal of the American Society of Nephrology (JASN). In the study, the researchers have examined the kidney function of a group of people between the ages of 50 and 70, and two groups of people between the ages of 70 to 95, to discover how the kidney function develops.

- What we see is that what happens in our kidneys when we age is representative of all the other things that happen in our bodies. The kidney function deteriorates, not because we get ill, but as part of ageing, Bjørn Odvar Eriksen explains, who is a Professor at the Department of Clinical Medicine at UiT and leader of the Metabolic and Renal Research Group.

Eriksen is the lead author of the article that has been published in JASN.

- Loss of kidney function is something that happens to all humans and is thus a way to determine ageing in general. There is still variation as to how quickly this happens, and we still do not have good answers as to why this variation occurs. We have examined many factors that can play a part as to why some of us experience larger loss of kidney function than others, he adds.

One of the groups that have participated in the study consists of over 1600 people and stems from The Tromsø Study, which is Norway's most comprehensive and best participated population study throughout 40 years. This group has been through the different examinations three times; between 2007 to 2009, 2013 to 2015, and 2018 to 2020. The last iteration of the study is still ongoing at The University Hospital of North Norway (UNN) and is lead by Associate Professor Toralf Melsom.

- No other study has done these kinds of examinations on a part of the normal population. That is why this study is so unique, Eriksen says.

The researchers use a precise method of measuring kidney function. They inject a substance into the blood veins that only separates into the kidneys, and let a few hours pass before they measure how much of the substance remains in the blood. This gives a measure of the kidney's ability to remove toxins and waste products. Eriksen explains that more people may experience loss of kidney function as it becomes more common to survive diseases like cancer and heart and vascular diseases.

- For those who experience loss of kidney function at a high age, this is a considerable burden. That is why this is an area that needs further research to find more answers. We are still looking for the fountain of youth, Eriksen says.

A new research letter reveals fewer people have been admitted to stroke centers in Michigan and northwest Ohio since the onslaught of the COVID-19 pandemic, and significantly fewer patients received a mechanical thrombectomy for their ischemic stroke.

The authors call COVID-19's influence on other critical illnesses like stroke a bystander effect. That's because time is of the essence for patients with stroke, but not everyone is getting to a comprehensive stroke center for needed care right now.

In the letter, researchers from Michigan Medicine with colleagues across the Michigan Stroke Treatment Improvement Collaborative reported a significant reduction in ischemic stroke admissions in March when compared both to February of this year (17.8%) and to March of 2019 . Similarly, rates of a procedure for ischemic stroke, mechanical thrombectomy, significantly declined this March compared to February and compared to March of 2019.

"A combination of patient fears, stringent patient transfer criteria, and health system strains may have contributed to lower ischemic stroke admissions as well as the near disappearance of thrombectomy procedures," the authors write.

The differences were most pointed in ischemic stroke and quantity of thrombectomy procedures, authors say, while there was less of a change compared to past months for hemorrhagic stroke.

Physician-scientists specializing in heart failure wanted to know: if their heart transplant patients contract COVID-19, would they have a different experience than the general public or others who are also immunosuppressed?

A team of Michigan Medicine Frankel Cardiovascular Center researchers, led by Matthew Konerman, M.D., identified 13 patients who had a previous heart transplant and were admitted to one of two hospitals in southeast Michigan in March or April for COVID-19 symptoms. All were black males.

"Despite immunosuppression, the clinical presentation and laboratory markers of disease severity showed similarities to what has been observed in the general population," says first author Scott Ketcham, M.D., an internal medicine resident physician. "However, almost half were critically ill and there was a higher rate of mortality than described among non-heart transplant recipients admitted with COVID-19."

The researchers recommend further research with a focus on racial and gender disparities in COVID-19 and on the identification of prognostic markers, treatments and appropriate immunosuppression management for patients with heart transplant with COVID-19.

Scientists have discovered new evidence for active volcanism next door to some of the most densely populated areas of Europe. The study 'crowd-sourced' GPS monitoring data from antennae across western Europe to track subtle movements in the Earth's surface, thought to be caused by a rising subsurface mantle plume. The work is published in Geophysical Journal International.

The Eifel region lies roughly between the cities of Aachen, Trier, and Koblenz, in west-central Germany. It is home to many ancient volcanic features, including the circular lakes known as 'maars'.

These are the remnants of violent volcanic eruptions, such as the one which created Laacher See, the largest lake in the area. The explosion that created this is thought to have occurred around 13,000 years ago, with a similar explosive power to the cataclysmic Mount Pinatubo eruption in 1991.

The mantle plume that likely fed this ancient activity is thought to still be present, extending up to 400km down into the Earth. However, whether or not it is still active is unknown: "Most scientists had assumed that volcanic activity in the Eifel was a thing of the past," said Prof. Corné Kreemer, lead author of the new study. "But connecting the dots, it seems clear that something is brewing underneath the heart of northwest Europe."

In the new study, the team - based at the University of Nevada, Reno and the University of California, Los Angeles in the United States - used data from thousands of commercial and state-owned GPS antennae all over western Europe, to map out how the ground is moving vertically and horizontally as the Earth's crust is pushed, stretched and sheared.

The research revealed that the region's land surface is moving upward and outward over a large area centred on the Eifel, and including Luxembourg, eastern Belgium and the southernmost province of the Netherlands, Limburg.

"The Eifel area is the only region in the study where the ground motion appeared significantly greater than expected," adds Prof. Kreemer. "The results indicate that a rising plume could explain the observed patterns and rate of ground movement."

The new results complement those of a previous study in Geophysical Journal International that found seismic evidence of magma moving underneath the Laacher See. Both studies point towards the Eifel being an active volcanic system.

The implication of this study is that there may not only be an increased volcanic risk, but also a long-term seismic risk in this part of Europe. The researchers urge caution however: "This does not mean that an explosion or earthquake is imminent, or even possible again in this area. We and other scientists plan to continue monitoring the area using a variety of geophysical and geochemical techniques, in order to better understand and quantify any potential risks."

Information about the new COVID-19 infection is constantly evolving based on what clinicians see firsthand. One constant, so far, is that the older population tends to fare worse than younger folks with this disease.

A team led by Daniel Goldstein, M.D., already studies aging and the influenza viral infection, and took this spring away from their lab to figure out if any of their other research, and other research they regularly read, could be helpful in the fight against COVID-19.

"Influenza is of course a different pathogen, but it may give some catalyst for research with the current SARS-CoV2 infection," says Goldstein, of the Michigan Medicine Frankel Cardiovascular Center. Goldstein, with Judy Chen, a doctoral student, and William Kelley, a postdoctoral research fellow, published a new review in the Journal of Immunology.

"We believe some of the phenomena that we're seeing with the current pandemic are similar to what we've seen in our research with aging," Goldstein says. "There seems to be a higher mortality because of dysregulated inflammation more than impaired viral control."

Additionally, increasing activation of neutrophils is reported in the current COVID-19 pandemic, which the authors have reported in their flu models. And how aging affects the immune system prior to infection is the same, and also potentially applicable in understanding the population afflicted by COVID-19, the authors say.

"However, there are certainly some unique things about this virus we're still learning," Goldstein says.

The effects of human presence on the social relationships of wild animals have rarely been studied. Even if the animals are not hunted or killed, increasing contact with humans could have profound indirect impacts. This is because proximity to humans could disturb the animals' ability to perform at tasks that are important for survival - such as feeding together or rearing young.

Researchers from the Department of Evolutionary Biology and Environmental Studies at the University of Zurich (UZH) have now taken a closer look at this topic by studying Masai giraffes in Tanzania. The study, carried out with researchers from the Max Planck Institute of Animal Behavior, the University of Konstanz and Pennsylvania State University, provides the first robust evidence that human presence affects the social structure in this iconic herbivore.

Mapping the social networks of giraffes

For their study, the scientists first needed to obtain large amounts of data from field research. "Detecting signals of natural versus human-caused influences on social relationships among wild animals is challenging," says Monica Bond, PhD candidate at the University of Zurich and first author of the study.

Over a period of six years, Bond and her research collaborators collected photographic data spanning 540 adult female Masai giraffes that live in a large, unfenced landscape in the Tarangire Ecosystem of Tanzania - an environment that features varying levels of anthropogenic (human-caused) disturbance. The researchers were able to identify individual giraffes by their unique and unchanging spot patterns. This resulted in one of the largest-scale social networks ever studied in a wild mammal.

Females live in groups

The field research sheds new light on the social relationships of giraffes: The female giraffes in Tarangire live in a complex multilevel society, with individuals preferring to associate with some females while avoiding others. These preferences result in discrete social communities of 60 to 90 females with little mixing among the groups, even when these share the same general area. "The study reveals that social structuring is clearly an important feature of female giraffe populations," says Barbara König, UZH professor and co-author of the study.

Humans disturb social groups

The data analysis also revealed that the social networks exhibit signs of disturbance when groups of giraffes are exposed to humans: Giraffes living closer to traditional compounds of indigenous Masai people have weaker relationship strengths and more exclusive social associations.

The researchers suspect that giraffes living near traditional human settlements are more likely to encounter livestock and humans. This potentially causes groups of giraffes to split up, even though they are tolerated by the Masai people. This disruption to the giraffes' social system - in addition to poaching, loss of habitat and changes in food supply - could be a reason why Masai giraffe populations have declined 50% in recent years.

Better protection for calves

In other research, the team found that groups of female giraffes with calves were more likely to occur closer to human settlements - possibly because this provides better protection from lions and hyenas. "It seems that female giraffes face a trade-off between maintaining important social bonds and reducing risk to their calves near these traditional settlements," explains Bond.

Overall, the study's results suggest that human presence could play an important role in determining the conservation future of this species of giraffe. Moreover, the study's leading-edge methodology highlights the importance of using the social network approach to reveal otherwise hidden potential causes of population declines.

Alcohol use disorders are associated with high social welfare and health care costs - but what causes them? A new Finnish study looks at the magnitude and reasons behind the economic burden alcohol use disorders have on society.

Earlier studies have shown that alcohol use disorders lead to various health and social problems, which cause an increase in the need and use of various services. However, the magnitude and distribution of the related costs have not been studied before.

Researchers at the University of Eastern Finland used a machine learning technique that is based on a Bayesian network model to analyse causal relationships between different risk factors and the costs associated with them. The analysis included a total of 16 risk factors, including socioeconomic variables such as age, gender, marital status, unemployment status, and social problems like homelessness, illicit drug use, criminal record, and drunk driving. The researchers also looked at what happens when a patient goes into remission, i.e., stops drinking altogether.

Funded by the Strategic Research Council at the Academy of Finland, the study was carried in collaboration between researchers at the University of Eastern Finland, the Finnish Institute for Health and Welfare, and Aalto University. They used a novel approach to control for confounding factors, allowing them to calculate a rough price tag for each risk factor.

The study population comprised 363 Finnish alcohol use disorder patients diagnosed in 2011-2012. Their data were collected from various patient information systems and social welfare databases over a period of five years.

Surprisingly, the number of diagnoses of chronic conditions played the biggest role in the overall cumulation of costs in patients with alcohol use disorder. In patients with at least two chronic conditions, the average 5-year costs of care were 26,000 euros (around 30,000 US dollars) higher than in patients without multiple diagnoses. The costs of care were also increased by earlier use of specialized care (and its high costs), receiving income support, and being over 55 years old. In addition, drug use, homelessness and the number of psychiatric diagnoses also increased the costs of care. Sustained abstinence, on the other hand, lowered the costs. A model created by the researchers shows that roughly 43% of alcohol use disorder patients who quit drinking belong to the lowest cost quartile, compared with the respective figure of 24% for current drinkers.

The findings shed light on how the cumulation of health and social problems increases the costs of social welfare and health care services.

"Since sustained abstinence reduces the costs of care, it would be wise to develop rehabilitation services and provide easy access to care. In addition, people with alcohol use disorders should also get better treatment for their non-alcohol related conditions," Early Stage Researcher and lead author of the article Elina Rautiainen from the University of Eastern Finland says.

Resistance to antibiotics has become a serious public health problem. Hospital infections, prostheses or surgical implants that become infected and do not respond to treatment are a real challenge to the research community, which has been seeking alternatives for effectively eliminating these bacteria for years. In 2012 the researchers from the Department of Chemical Engineering of the Universitat Rovira i Virgili, Vladimir Baulin and Sergey Pogodin, opened a line of research to develop antibacterial models that were inspired by insects. The wings of, for example, dragon flies are made up of complex structures of nanometric geometric shapes, which are highly efficient at killing bacteria. In their attempt to understand these forms and reproduce them as new anti-bacterial materials, a team consisting of Vladimir Baulin, Marc Werner, from the Leibniz-Institut für Polymerforschung (Dresden, Germany) and Elena Ivanova from the Australian university RMIT, discovered that the elasticity of nanopillars is a key factor because they can retain and release sufficient energy to kill the bacteria.

The line of research that had been initiated years before had already found that the wings of these insects are made up of a structure of nanopillars that eliminates bacteria mechanically, which is known as the biocide effect. These mechano-bactericidal properties, by which bacteria are killed almost instantly when they come into contact with the pillars without any need to use a chemical substance, raises numerous questions that researchers are attempting to answer by experimenting with different shapes and geometries that will help them to understand which has the most efficient bactericidal effect.

They investigated the bactericidal capacity on nanometric surfaces by varying the height of the pillars and keeping the other dimensions constant. The results, which have just been published in the journal PNAS, have shown that the flexibility of these pillars is closely connected to their appearance. "Even the solid and rigid materials become flexible if one of the dimensions is much longer than the others (for example, a guitar string or a long pillar)," says Vladimir Baulin. The researchers have developed a physical model that shows that when bacteria come into contact with these pillars they can accumulate elastic energy even at such a small scale. Thanks to this model it is now possible to calculate the elastic response of other structures and optimise their antibacterial properties.

The deformation forces of the pillar caused by the contact of the bacteria are so high that they can even break the bacteria's cell wall, thus providing a new mechanism for killing them. These forces are associated with surface tensions imposed on the bacterial cells. The pillars under the bacteria that approach stretch more at the edges, whereas the pillars located under the centre of the bacteria practically do not change. The study shows, then, that the gradual variation in the height of the pillars of a nanometric surface can determine their bactericidal efficacy.

This discovery may lead to a completely new class of antibacterial materials, which could range from packaging for food to filters or masks. Unlike traditional filters, where the bacteria remain but are not deactivated, the new nanoscale elastic material can safely kill the bacteria in a matter of minutes, which means that they cannot activate any defence mechanisms or give any resistance at all," concluded Baulin.

When humans get infected by pathogenic bacteria, the body's immune system tries to eliminate the intruders. One way of doing this is by launching an inflammatory response - a cascade of events that includes the expression of protective proteins, the activation of immune cells, and a process of controlled cell death when infected cells can't be saved.

Scientists including members of EMBL's Typas group, members of the group of EMBL alumnus Jeroen Krijgsveld at the German Cancer Research Center (DKFZ) in Heidelberg, and other collaborators have investigated how immune cells called macrophages respond to infection by the intracellular pathogen Salmonella enterica. The scientists applied a method recently developed in their labs to enrich, identify, and quantify all newly produced proteins from Salmonella-infected macrophages. They marked newly produced proteins with a specific chemical label and identified them using a technique called mass spectrometry, which allowed them to analyse the entire set of cellular proteins. Importantly, the scientists measured protein levels in macrophages at different infection stages and across different cell compartments. Their study, which is published in Nature Microbiology, shows that monitoring the dynamic changes in protein production and targeting can reveal new insights into the mechanisms by which cells respond to pathogens.

One of the unexpected findings of the study was that a well-known family of proteins called cathepsins move to a new location when cells get infected by Salmonella. Cathepsins are proteases - proteins that break down other proteins. They're normally kept inside small subcellular structures known as lysosomes and have previously been implicated in promoting cell death, although the mechanism or any link between the process and bacterial infection were unknown. The scientists have now discovered that Salmonella causes newly produced cathepsins to accumulate in the nuclei of infected cells. The protein-degrading activity of cathepsins in the nucleus is then required to initiate an inflammatory form of programmed cell death.

The new study shows the benefit of systematically following protein dynamics during infection, which can unravel new pathways and mechanisms the host uses to defend itself against pathogens.

Researchers at the Nanoscience Center and at the Faculty of Information Technology at the University of Jyväskylä in Finland have demonstrated that new distance-based machine learning methods, developed in the University of Jyväskylä, are capable of predicting structures and atomic dynamics of nanoparticles reliably. The new methods are significantly faster than traditional simulation methods used for nanoparticle research and will facilitate more efficient explorations of particle-particle reactions and particles' functionality in their environment. The study was published in a Special Issue devoted to machine learning in The Journal of Physical Chemistry on May 15, 2020.

The new methods were applied to ligand-stabilized metal nanoparticles, which have been long studied at the Nanoscience Center at the University of Jyväskylä. Last year, the researchers published a method that is able to successfully predict binding sites of the stabilizing ligand molecules on the nanoparticle surface. Now, a new tool was created that can reliably predict potential energy based on the atomic structure of the particle, without the need to use numerically heavy electronic structure computations. The tool facilitates Monte Carlo simulations of the atom dynamics of the particles at elevated temperatures.

Potential energy of a system is a fundamental quantity in computational nanoscience, since it allows for quantitative evaluations of system's stability, rates of chemical reactions and strengths of interatomic bonds. Ligand-stabilized metal nanoparticles have many types of interatomic bonds of varying chemical strength, and traditionally the energy evaluations have been done by using the so-called density functional theory (DFT) that often results in numerically heavy computations requiring the use of supercomputers. This has precluded efficient simulations to understand nanoparticles' functionalities, e.g., as catalysts, or interactions with biological objects such as proteins, viruses, or DNA. Machine learning methods, once trained to model the systems reliably, can speed up the simulations by several orders of magnitude.

The new method allowed simulations to be run on a laptop or desktop

In this work the researchers used the potential energies, predicted by the machine learning method, to simulate the atomic dynamics of thiol-stabilized gold nanoparticles. The results were in good agreement with the simulations performed by using the density functional theory. The new method allowed simulations to be run on a laptop or desktop in a time scale of a few hours while the reference DFT simulations took days in a supercomputer and used simultaneously hundreds or even thousands of computer cores. The speed-up will allow long-time simulations of the particles' structural changes and particle-particle reactions at elevated temperatures.

The researchers used a distance-based machine learning method developed in the group of professor Tommi Kärkkäinen in Jyväskylä. It describes each momentary atomic configuration of a nanoparticle by calculating a so-called descriptor, and compares distances between descriptors in a multi-dimensional numerical space. By using correlations to a training set created by the reference DFT simulations, the potential energy can be predicted. This approach, used now for the first time in nanoparticle research, is simpler and more transparent than traditionally used neural networks.

"It is extremely motivating that we can reduce the computational load from running simulations in supercomputers to running them with similar quality in a laptop or a home PC", says PhD student Antti Pihlajamäki who is the lead author of the study.

"It was a great surprise that our relatively simple machine learning methods work so well for complicated nanostructures", states professor Tommi Kärkkäinen.

"In the next phase, our target is to generalize the method to work well for nanoparticles of many different sizes and chemical compositions. We will still need supercomputers to generate enough high-quality data to train the machine learning algorithm, but we hope that in the future we can move to use these new methods primarily to studies of nanoparticle functionality in complicated chemical environments", summarizes Academy Professor Hannu Häkkinen, who coordinated the study.

Studies by Monash Biomedicine Discovery Institute (BDI), have provided a new understanding into the roles two essential amino acids play in metabolic health, which may help scientists in the fight against obesity.

Led by Dr Adam Rose , the recent finding, published in Nature Communications, shows that by reducing the amount of two amino acids - threonine and tryptophan - in young healthy mice, they were able to burn more calories than they consumed, without calorie reduction, keeping them lean and healthy and without the side-effect of lower muscle mass. A low-threonine diet even protected mice that were morbidly obese and prone to developing type 2 diabetes.

While a moderate reduction in dietary protein and therefore essential amino acids can enhance vitality, diets devoid of this component can make people sick very quickly and are not recommended. However, this study has shown that a reconsideration of the functions of these two amino acids in nutrition warrants further exploration.

"Once we understand which particular dietary components are needed for the health-promoting effects of these diets we can design strategies to mimic them, simulating the effects without having the negative side effects," Dr Rose said.

A highlight of the study was an experiment where Dr. Rose and his team genetically manipulated the mice to be able to synthesise the essential amino acid threonine, which blocked the health promoting effects of the low threonine diet and saw the mice gain weight, proving that these two amino acids can hold the key to a new diet approach.

Dr Matthew Piper, a key co-author adds, "We are finding an increasing number of situations in which essential amino acids are powerful modulators of lifelong health and lifespan. Our findings on their specific effects gives us exciting insights into how we might harness their benefits to drive better health."

Co-author Professor Stephen Simpson of the University of Sydney's Charles Perkins Centre said, "We are beginning to understand how critical the balance of dietary amino acids is to the control of appetite, health and ageing."