Culture

TAMPA, Fla (June 21, 2021) -- A blood gene profile associated with a high risk of dying from a severe lung disease can also predict poor outcomes in patients with COVID-19, a multicenter retrospective study led by the University of South Florida Health (USF Health) demonstrated. The risk profile based on 50 genes could help customize how COVID-19 is treated, improve allocation of limited health care resources such as intensive care beds and ventilators, and potentially save lives.

Idiopathic pulmonary fibrosis (IPF), a disease of unknown cause, affects the lung interstitium or the space between the lung sacs and the bloodstream, leading to severe lung scarring. Severe COVID-19 can also damage the lung interstitium leading to severe lung scarring.

"Our study identified at the molecular level, a gene risk profile that predicts worse COVID-19 outcomes before the patient becomes severely ill," said principal investigator Jose Herazo-Maya, MD, an associate professor and associate chief of pulmonary, critical care and sleep medicine at the USF Health Morsani College of Medicine. "That means every patient with COVID-19 could potentially get a blood test that could tell us if they are at high or low risk of dying... And if we know in advance who will likely end up in the ICU and who will likely do well recovering at home with appropriate monitoring, we can tailor our interventions to individual patients based on their level of risk."

The USF Health study appeared online June 20 in EBioMedicine, a publication of THE LANCET. It builds upon previous genomic research by Dr. Herazo-Maya and colleagues at Yale School of Medicine. In 2017, they led an international team that studied and validated a gene expression signature in the blood that reliably forecasts the likelihood of IPF mortality. (Certain patients with lung scarring can live well for years, while others develop worsening disease and die quickly from IPF.)

As the COVID-19 pandemic unfolded, "the basic question we had was 'Can we repurpose the gene signature known to predict mortality in a fibrotic lung disease to predict mortality in those infected with a new coronavirus that can cause lung fibrosis as well?" said the EBioMedicine paper lead author Brenda Juan-Guardela, MD, assistant professor of medicine at the USF Health Morsani College of Medicine and medical director of Respiratory Care Services at Tampa General Hospital (TGH). "To the best of our knowledge, this study is the first to compare overlapping immune gene profiles in COVID-19 and IPF, which were remarkably similar."

The USF Health-led team analyzed gene expression patterns of 50 genes known to predict IPF mortality in three COVID-19 cohorts and two IPF cohorts. The researchers used a molecular scoring system to distinguish between high versus low-risk gene profiles in all five cohorts.

Among their findings:

In the COVID-19 validation cohorts, a 50-gene high risk profile was linked to greater risk of ICU admission, mechanical ventilation, and in-hospital death.

The researchers also performed single-cell, gene expression analyses and identified specific immune cells -- monocytes, neutrophils, and dendritic cells - as the primary source of gene expression changes in the high-risk, COVID-19 gene profile. This finding suggests COVID-19 and IPF may share common innate and adaptive immune responses that trigger lung scarring.

The 50-gene risk profile in COVID-19 can also predicts mortality in IPF at the exact same threshold.

At TGH, Dr. Herazo-Maya treats previously hospitalized COVID-19 patients who come to the Center for Advanced Lung Disease with severe lung fibrosis; some are being evaluated for lung transplantation. "Even though coronavirus cases are dropping, that doesn't mean all the patients will recover without complications," he said. "We're starting to see the damaging, long-term effects in the lungs of some COVID-19 survivors."

While more studies are needed, researchers and clinicians may soon be able to apply the gene risk profiles to help advance the care of both COVID-19 and IPF patients, Dr. Herazo-Maya said. His laboratory is currently developing a blood test, based on these genes, that can be easily applied in clinical practice to predict poor disease outcomes.

Besides outcome prediction, the identification of 50-gene risk profiles may also have significant therapeutic potentials. For example, a 10-day regimen of the steroid dexamethasone, a drug that suppresses the immune system, has been shown to increase survival of patients hospitalized with COVID-19.

Immunosuppressant drugs have been essentially discontinued for IPF treatment because they increase mortality when given at high doses and in combination over long periods, Dr. Herazo-Maya said. "But perhaps we could investigate the use of dexamethasone or a similar steroid treatment for a short period of time in a subgroup of IPF patients with a 50-gene high risk profile, using the principle of precision or personalized medicine."

The 50-gene high risk profile may also support the rationale to investigate the use of targeted IPF antifibrotic medications, which slow the rate of lung scarring, to prevent short and long-term sequelae of COVID-19, he added.

DURHAM, N.C. - In the fight against viruses, antibodies have the potential to either block infection or enable infection and make the disease worse, leading to concern about their use as a therapy for COVID-19.

In a study published in the journal Cell, Duke investigators demonstrated in mice and monkeys that human antibodies lacked the ability to make SARS-CoV-2 infection worse and, instead, exerted their defensive powers against the infection. The findings help reinforce evidence that antibodies are safe when given as treatments or induced by COVID-19 vaccines.

The two types of antibodies -- those that neutralize the virus or those that enhance virus replication -- have been the subjects of much research, raising concerns that antibodies could potentially trigger severe infections in some recipients.

But the current research, led by scientists at the Duke Human Vaccine Institute, is the first to use animal models to examine what occurs when SARS-CoV-2 antibodies are tested with the virus.

"Our study, using mice and monkeys, demonstrates that antibodies that are potentially harmful in the test tube do not appear to be harmful in the setting of SARS-CoV-2 infection in mice or monkeys," said co-senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI).

"We tested a number of disease-enhancing antibodies in mouse and monkey experiments -- multiple trials with different antibodies -- and determined that disease enhancement does not occur in the animals, and that's good news for the development of effective treatments and vaccines." Haynes said.

Senior author Kevin Saunders, Ph.D., director of research at DHVI, isolated more than 1,700 antibodies from people who had COVID and screened them for their effects on the virus.

"We quickly found a set that were capable of blocking infection, including a set of antibodies that are candidates for clinical trials to prevent people from getting COVID," Saunders said. "We also found a set of antibodies that, instead of preventing infection in tissue culture, they enhanced infection in the test tube."

But in tests administering the antibodies to mice and monkeys, there were no such effects in the body that could be attributed to antibody administration. The presence of the infection-enhancing antibodies also did not counter how well the protective antibodies functioned in the body.

"These results in animal models suggest that SARS-CoV-2 antibody treatments or the induction of SARS-CoV-2 antibodies by vaccination have a low likelihood of exacerbating COVID-19 disease in humans," Saunders said. "Our findings are immediately applicable to COVID-19 vaccine candidates under development in use, and to antibodies and plasma being used to treat COVID-19."

A team of scientists from NUST MISIS and MIPT have developed and tested a new platform for realization of the ultra-strong photon-to-magnon coupling. The proposed system is on-chip and is based on thin-film hetero-structures with superconducting, ferromagnetic and insulating layers. This discovery solves a problem that has been on the agenda of research teams from different countries for the last 10 years, and opens new opportunities in implementing quantum technologies. The study was published in the highly ranked journal Science Advances.

The last decade has seen significant progress in the development of artificial quantum systems. Scientists are exploring different platforms, each with its own advantages and disadvantages. The next critical step for advancing quantum industry requires an efficient method of information exchange between platform hybrid systems that could benefit from distinct platforms. For example, hybrid systems based on collective spin excitations, or magnons, are being developed. In such systems, magnons must interact with photons, standing electromagnetic waves trapped in a resonator. The main limiting factor for developing such systems is the fundamentally weak interaction between photons and magnons. They are of different sizes, and follow different dispersion laws. This size difference of a hundred times or more considerably complicates the interaction.

Scientists from MIPT together with their colleagues managed to create a system with what is called the ultra-strong photon-to-magnon coupling.

Vasily Stolyarov, deputy head of the MIPT Laboratory of Topological Quantum Phenomena in Superconducting Systems, commented: "We created two subsystems. In one, being a sandwich from superconductor/insulator/superconductor thin films, photons are slowed down, their phase velocity is reduced. In another one, which is also a sandwich from superconductor/ferromagnetic/superconductor thin ?lms, superconducting proximity at both interfaces enhances the collective spin eigen-frequencies. The ultra strong photon-to-magnon coupling is achieved thanks to the suppressed photon phase velocity in the electromagnetic subsystem."

Igor Golovchanskiy, leading researcher, senior researcher at the MIPT Laboratory of Topological Quantum Phenomena in Superconducting Systems, head of the NUST MISIS Laboratory of Cryogenic Electronic Systems, explained: "Photons interact very weakly with magnons. We managed to create a system in which these two types of excitations interact very strongly. With the help of superconductors, we have significantly reduced the electromagnetic resonator. This resulted in a hundred times reduction of the phase velocity of photons, and their interaction with magnons increased by several times."

This discovery will accelerate the implementation of hybrid quantum systems, as well as open up new possibilities in superconducting spintronics and magnonics.

WASHINGTON -- Although quantum technology has proven valuable for highly precise timekeeping, making these technologies practical for use in a variety of environments is still a key challenge. In an important step toward portable quantum devices, researchers have developed a new high-flux and compact cold-atom source with low power consumption that can be a key component of many quantum technologies.

"The use of quantum technologies based on laser-cooled atoms has already led to the development of atomic clocks that are used for timekeeping on a national level," said research team leader Christopher Foot from Oxford University in the U.K. "Precise clocks have many applications in the synchronization of electronic communications and navigation systems such as GPS. Compact atomic clocks that can be deployed more widely, including in space, provide resilience in communications networks because local clocks can maintain accurate timekeeping even if there is a network disruption."

In The Optical Society (OSA) journal Optics Express, S. Ravenhall, B. Yuen and Foot describe work carried out in Oxford, U.K. to demonstrate a completely new design for a cold atom source. The new device is suitable for a wide range of cold-atom technologies.

"In this project we took a design we made for research purposes and developed it into a compact device," said Foot. "In addition to timekeeping applications, compact cold-atom devices can also be used for instruments for gravity mapping, inertial navigation and communications and to study physical phenomena in research applications such as dark matter and gravitational waves."

Cooling atoms with light

Although it may seem counterintuitive, laser light can be used to cool atoms to extremely low temperatures by exerting a force that slows the atoms down. This process can be used to create a cold-atom source that generates a beam of laser-cooled atoms directed toward a region where precision measurements for timekeeping or detecting gravitational waves, for example, are carried out.

Laser cooling usually requires a complicated arrangement of mirrors to shine light onto atoms in a vacuum from all directions. In the new work, the researchers created a completely different design that uses just four mirrors. These mirrors are arranged like a pyramid and placed in a way that allows them to slide past each other like the petals of a flower to create a hole at the top of the pyramid through which the cold atoms are pushed out. The size of this hole can be adjusted to optimize the flow of cold atoms for various applications. The pyramid arrangement reflects the light from a single incoming laser beam that enters the vacuum chamber through a single viewport, thus greatly simplifying the optics.

The mirrors, which are located inside the vacuum region of the cold-atom source, were created by polishing metal and applying a dielectric coating. "The adjustability of this design is an entirely new feature," said Foot. "Creating a pyramid from four identical polished metal blocks simplifies the assembly, and it can be used without the adjustment mechanism."

Better measurements with more atoms

To test their new cold-atom source design, the researchers constructed laboratory equipment to fully characterize the flux of atoms emitted through a hole at the apex of the pyramid.

"We demonstrated an exceptionally high flux of rubidium atoms," said Foot. "Most cold-atom devices take measurements that improve with the number of atoms used. Sources with a higher flux can thus be used to improve measurement accuracy, boost the signal-to-noise ratio or help achieve larger measurement bandwidths."

The researchers say that the new source is suitable for commercial application. Because it features a small number of components and few assembly steps, scaling up production to produce multiple copies would be straightforward.

The human intestine is made up of more than 40 square meters of tissue, with a multitude of folds on its internal surface that resemble valleys and mountain peaks in order to increase the absorption of nutrients. The intestine also has the unique characteristic of being in a continuous state of self-renewal. This means that approximately every 5 days all the cells of its inner walls are renewed to guarantee correct intestinal function. Until now, scientists knew that this renewal could take place thanks to stem cells, which are protected in the so-called intestinal crypts, and which give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells towards the intestinal peaks was unknown.

Now, an international team led by Xavier Trepat, ICREA Research Professor and Group Leader at the Institute for Bioengineering of Catalonia (IBEC), in collaboration with the IRB, researchers from the UB and UPC universities in Barcelona, and the Curie Institute of Paris, has deciphered the mechanisms leading the crypts to adopt and maintain their concave shape, and how the migration movement of the cells towards the peaks occurs, without the intestine losing its characteristic folded shape. The study, published in the prestigious journal Nature Cell Biology, has combined computer modelling, led by Marino Arroyo, professor at the UPC, researcher associated with IBEC and member of CIMNE, with experiments with intestinal organoids from mouse cells, and shows that this process is possible thanks to the mechanical forces exerted by the cells. An important part of this study has been supported by the "la Caixa" Foundation within the framework of the CaixaResearch programme. The entity has also awarded a scholarship to the first co-author, Gerardo Ceada, to carry out his PhD at IBEC.

The forces determine and control the shape of the intestine and the movement of the cells

Using mouse stem cells and bioengineering and mechanobiology techniques, researchers have developed mini-intestines, organoids that resemble the three-dimensional structure of peaks and valleys, recapitulating tissue functions in vivo. Using microscopy technologies developed by the same group, researchers carried out high-resolution experiments for the first time that have allowed them to obtain 3D maps showing the forces exerted by each cell.

In addition, with this in vitro model, scientists have shown that the movement of new cells to the peak is also controlled by mechanical forces exerted by the cells themselves, specifically by the cytoskeleton, a network of filaments that determines and maintains cell shape.

"Contrary to what was believed up until now, we have been able to determine that it is not the cells of the intestinal crypt that push the new ones up, but that it is the cells at the peak pulling the new ones up, akin to a mountaineer who helps another climber by pulling them up", explains Gerardo Ceada from IBEC

"With this system, we have discovered that the crypt is concave because the cells have more tension on their upper surface than on the bottom, which causes them to adopt a conical shape. When this occurs in several cells next to each other, the result is that the tissue folds, giving rise to a pattern of peaks and valleys", adds Carlos Perez-Gonzalez, (IBEC and Curie Institute).

The new mini-intestine model will allow further studies of diseases such as cancer, celiac disease or colitis to be conducted in reproducible and real conditions, in which there is an uncontrolled proliferation of stem cells or a destructuring of the folds. In addition, intestinal organoids can be manufactured with human cells and used for the development of new drugs or for the study of the intestinal microbiota.

LAWRENCE -- Tulsa may not be the first town one thinks of when talking about jazz, and flood management may not be the first vocation one compares to the musical genre. But the success Tulsa displayed in going from one of the nation's most flood-prone cities to a nationally recognized model of long-term risk reduction in just two decades is analogous to the evolution of one of the most American styles of music, a University of Kansas professor points out in a new study.

Tulsa, the second-largest city in Oklahoma, suffered several devastating floods in the 1970s and 1980s, then became a national model for flood mitigation by the 1990s. What hasn't been studied closely is how a group of engineers, planners, government officials, journalists, attorneys and citizens came together as a network of champions that adapted and evolved over a period of decades.

Ward LylesWard Lyles, associate professor of public affairs & administration at KU, co-wrote a study with Penn Pennell, KU urban planning graduate, and Rachel Riley of the University of Oklahoma detailing the group central to Tulsa's success. It was published in the journal Natural Hazards Review. The authors conducted interviews with local champions from multiple professions who began work on a flood mitigation plan in the 1970s, two of whom remained active in the work well into the 2000s, Ron Flanagan and journalist Ann Patton.

After a rapid succession of floods in the early 1970s, residents and some of the local professionals, functioning similarly to a loosely organized improvisational jazz band, seized the "window of opportunity" to press for change. Myriad approaches were pursued, including buying and demolishing homes in the floodplain and building more flood control structures. However, the band's style fell out of favor, so to speak, when a more conservative city government came to power in the late '70s and instituted more developer-friendly policies focused more on growth than floodplain safety. In their own words, some of the local champions were "exiled" from work in Tulsa and had to find jobs in other states. Meanwhile, flood control efforts cooled.

Tulsa U.S. 66 highway signTulsa suffered another devastating event, the "Memorial Day Flood" of 1984, just weeks after the election of new city leadership dedicated to renewing the commitment to flood mitigation. In subsequent years, members of the original band came back together and became more of a swing-style big band with organized sections compared to its more loosely arranged organization it the 1970s. Engineers, planners, attorneys, local residents and elected officials worked in concert to amplify and extend the efforts of the 1970s. Large swaths of flood-prone homes were purchased and the land was converted to open space suited to recreation and, when needed, flood storage. Land use regulations, engineered structure and education programs helped Tulsa become one of the dozen or so leading flood reduction communities in the early 1990s, when the Federal Emergency Management Agency initiated a program that rewarded proactive communities with lower insurances rates for residents.

The evolution was so successful that Tulsa received a major infusion of federal grant support in the late 1990s, cementing the transition of Tulsa's mitigation jazz band from a popular local group to a nationally emulated act, the authors wrote. A novel local nonprofit spun out of this effort and became a jazz institute of sorts, engaging more deeply with the Tulsa community on other hazards like tornadoes, and extending its work more broadly across the state of Oklahoma. The successful evolution illustrates many key points of successful city planning and management; namely, the importance of weaving together a network of many local champions committed to thinking long term, as opposed to the common approach of dealing with disasters solely in the moment and mainly by depending on narrow groups of experts to set policy.

"Our approach nationally has long been to try to engineer your way out of disasters, frantically respond to them when they happen, or not deal with them at all," Lyles said. "We often fail to think carefully about how land use and infrastructure decisions expose the entire community to risk until it is too late. Floods are a perfect example of this problem because flooding happens along rivers and streams, and we know very precisely where they are. The same tends to be true of areas at risk from hurricanes and wildfires, in contrast to tornados, which touch down randomly within a community."

Through the study, the interviewees revealed the critical importance of having a diverse group of local champions with a wide-ranging set of skills, not only in professional expertise like engineering, planning or law, but perhaps most importantly in communication and collaboration. Varied skills and leadership styles among these champions provided adaptability and resilience to the network but also posed challenges, the authors wrote. A key finding of the study is the role Patton played in facilitating and managing relationships, sometimes between people with very different communication styles, political attitudes and even core beliefs. Patton's professional journey - as a journalist working the "Black beat" in Tulsa in the 1970s, as a political operative and government official in the 1970s through the 1990s and a nonprofit entrepreneur in the 2000s -- is all the more remarkable because she completed her college degree just shy of turning 80 years old in the 2010s.

Emergency response groups regularly feature experts who leverage skills in fire, law enforcement and logistics to prepare for and respond to events. The same is true for city planners, engineers and other public service professionals whose responsibilities relate more to long-term risk reduction. But, across each of these professions, historically dominated by older, white males, the so-called "soft skills" of emotional intelligence, social intelligence and cultural humility -- just the kinds of skills Patton exhibited on top of her more traditional expertise -- are often minimized or ignored in favor of technical skills or specialized forms of knowledge.

"The thing we don't talk enough about in managing disasters - including public health emergencies like COVID -- is critical importance of the 'special sauce' of relationship skills essential for fostering, sustaining and harnessing a diverse and dynamic network of people," said Lyles, who has written previously on the value of caring as part of public planning. "You need someone who can help deploy the hard skills with the soft skills."

That aspect is true in a city like Tulsa with a dark history of race relations, just as it is in any location that has people of different backgrounds, cultures and experiences living together, he added. The experiences of Tulsa and others who have successfully, or even unsuccessfully, handled emergency response and planning have a great deal of parallels to the current COVID-19 pandemic response, as political differences, poor collaboration, egos and poor communication hampering responses on national, state and local levels. Understanding differences, or cultural competence, paired with cultural humility, or acknowledging that one does not completely understand the experience of others, could go a long way in improving responses to current disasters and preparation for those that will come in the future.

"It shouldn't be revolutionary that relationships matter," Lyles said. "But it takes skill to weave relationships together. It's not enough to be professionally passionate. We need social and emotional intelligence as well, and especially cultural humility."

All coronaviruses produce four primary structural proteins and multiple nonstructural proteins. However, the majority of antibody-based SARS-CoV-2 research has focused on the spike and nucleocapsid proteins. A study published in PLOS Biology by Anna Heffron, Irene Ong and colleagues at the University of Wisconsin-Madison, USA, suggests that immune responses may develop against other proteins produced by the SARS-CoV-2 virus.

The efficacy of spike protein-based vaccines is variable and not everyone infected with SARS-CoV-2 produces detectable antibodies against the spike or nucleocapsid proteins. Therefore, expanded antibody-based options have the potential to play an important role in improving vaccines, diagnostics, and therapeutics, particularly given the emergence of new variants. To investigate whether SARS-CoV-2 infection induces robust antibody responses against all SARS-CoV-2 proteins, researchers mapped 79 "epitopes" - specific regions of the viral proteome that antibodies recognize and bind to. They also tested whether antibodies that develop in response to SARS-CoV-2 or existing antibodies from previous exposures to coronaviruses might bind to any of the proteins in the six other known human coronaviruses to identify potential cross-reactive epitopes.

In addition to spike and nucleocapsid proteins, the authors located previously unknown, highly reactive B cell epitopes throughout the full array of proteins in SARS-CoV-2 and other coronaviruses, expanding the potential for future vaccine and therapeutic development. Future research is needed, however, to determine how long these antibodies remain and whether responses of vaccinated individuals differ from those who contracted COVID-19 prior to vaccination. Dr. Ong and colleagues will continue to investigate these aspects in adults and children.

Although the authors did not directly profile variants of concern that have emerged since the beginning of the COVID-19 pandemic, a comparison of the original SARS-CoV-2 genome with a few of the variants of concern identified numerous variations in regions that are at or within 3 amino acids of identified antibody binding epitopes.

According to the authors, "Our extensive profiling of epitope-level resolution antibody reactivity in COVID-19 convalescent subjects, confirmed by independent assays, provides new epitopes that could serve as important targets in the development of improved diagnostics, vaccines, and therapeutics against SARS-CoV-2, variants of concern, and dangerous human coronaviruses that may emerge in the future".

Think about how many different pieces of technology the average household has purchased in the last decade. Phones, TVs, computers, tablets, and game consoles don't last forever, and repairing them is difficult and often as expensive as simply buying a replacement.

Electronics are integral to modern society, but electronic waste (e-waste) presents a complex and growing challenge in the path toward a circular economy--a more sustainable economic system that focuses on recycling materials and minimizing waste. Adding to the global waste challenge is the prevalence of dishonest recycling practices by companies who claim to be recycling electronics but actually dispose of them by other means, such as in landfills or shipping the waste to other countries.

New research from the Hypothetical Materials Lab at the University of Pittsburgh Swanson School of Engineering develops a framework to understand the choices a recycler has to make and the role that digital fraud prevention could have in preventing dishonest recycling practices.

"Electronics have huge environmental impacts across their life cycle, from mining rare raw materials to the energy-intensive manufacturing, all the way to the complicated e-waste stream," said Christopher Wilmer, the William Kepler Whiteford Faculty Fellow and associate professor of chemical and petroleum engineering, who leads the Hypothetical Materials Lab. "A circular economy model is well-suited to mitigating each of these impacts, but less than 40 percent of e-waste is currently estimated to be reused or recycled. If our technology is going to be sustainable, it's important that we understand the barriers to e-waste recycling."

Some U.S. firms that have touted safe, ethical and green recycling practices never actually recycle much of what they receive; instead, their e-waste was illegally stockpiled, abandoned or exported. Between 2014 and 2016, the Basel Action Network used GPS trackers in electronics delivered to U.S. recyclers, showing that 30 percent of the products ended up overseas.

The researchers developed a model framework that analyzes dishonest end-of-life electronics management and what leads recyclers to pursue fraudulent activities. They find that the primary way to ensure an e-waste recycler will engage in honest practices with minimum supervision is to make it the more profitable option, either by decreasing the costs of recycling or increasing the penalties for fraudulent practices.

"The main barrier to honest recycling is its cost," said lead author Daniel Salmon, a graduate student in the Department of Electrical and Computer Engineering. "One of our main findings is that if we find a way to make it more profitable for companies to recycle, we will have less dishonest recycling. Targeted subsidies, higher penalties for fraud and manufacturers ensuring their electronics are more easily recyclable are all things that could potentially solve this problem."

The researchers also suggest the use of the blockchain as neutral, third-party supervision to avoid fraudulent recycling practices.

"Our model mentions the influence of monitoring and supervision, but self-reporting by companies enables dishonesty. On the other hand, something like the blockchain does not," said Wilmer, who founded Ledger, the first peer-reviewed scholarly journal dedicated to blockchain and cryptocurrency. "Relying on an immutable record may be one solution to prevent fraud and align behaviors across recyclers toward a circular economy."

The work is part of a larger NSF-funded convergence research project on the circular economy, which is led by Melissa Bilec, deputy director of the Mascaro Center, associate professor of civil and environmental engineering, and Roberta A. Luxbacher Faculty Fellow at Pitt.

In recent years, many juvenile courts have adopted in-home detention with electronic monitoring tethers as an alternative to institutional incarceration. A new study examined whether this approach reduces recidivism among girls involved in the juvenile justice system. The study found that tethers failed to reduce reoffending among the girls; in fact, they may be harmful because in-home detention limits girls' access to treatment programs.

The study, by researchers at the University of Cincinnati (UC) and Michigan State University, appears in Justice Evaluation Journal, a publication of the Academy of Criminal Justice Sciences.

"We believe this is the first study to examine tethers' effectiveness among girls," says Valerie R. Anderson, assistant professor of criminal justice at UC, who led the study. "Most criminal justice practices and policies have been developed for and tested on boys and men, then applied to girls. Our study will help inform policy and evidence-based practice for adjudicated girls."

In-home detention with electronic monitoring (or tethers) has been used widely among adults. Individuals are confined to home and wear tethers so their location can be monitored at all times; tethers are used primarily to ensure compliance with detention requirements, not necessarily to restrict those sentenced from leaving home.

Juvenile courts have begun to use this approach to reduce youth's future delinquency and involvement with the criminal justice system. Tethers are considered an alternative to residential placement as well as an early release alternative to institutional options for continued secure detention, but their effectiveness for girls is unclear.

In this study, researchers used data from a midsized Midwestern juvenile family court's delinquency and truancy divisions between 2004 and 2012. They evaluated the effectiveness of in-home detention with tethers on recidivism rates, comparing 155 girls who received in-home detention with tethers to a control group of 155 girls with characteristics similar to the first group who received either curfews or in-home detention without tethers. The girls' average age was 14 when they had their first contact with the courts, and most were youth of color.

Researchers assessed the girls on 41items across eight domains, including prior/current offenses, education, leisure and recreation, peer relationships, substance abuse, family circumstances, attitudes and orientation, and personality. They measured recidivism by whether girls received new court petitions one and two years after sentencing.

The study found that in-home detention tethers were not effective in reducing recidivism for girls. Girls who received a tether had significantly higher rates of recidivism two years after release from in-home detention (52 percent) than girls who did not receive a tether (35 percent).

The study also found that court petitions were more likely to be related to persons for girls who had been tethered; both tethered and nontethered girls had the same distribution across other types of offenses (e.g., property, drugs, status--offenses such as running away from home and truancy from school).

The authors suggest that gender-specific experiences of adjudicated girls may place them at greater risk for recidivism after at-home detention with tethers. Descriptive analyses of the girls sentenced to electronic monitoring showed that they had significantly higher scores on a measure of risk assessment that measured education, substance abuse, family dynamics, and other factors. This indicates that the girls likely required intensive levels of treatment and support, but by being restrained at home with electronic monitoring, they may have been restricted from fully engaging in treatment programs that could have led to reductions in their risk of recidivism.

In addition, tethering places girls under closer scrutiny, increasing opportunities for probation officers to observe violations, which may lead to new court petitions, the authors explain. And placing girls in homes that may be unstable and where they may experience domestic violence may further exacerbate girls' risk of reoffending.

"In-home detention with tethers is touted as more cost-effective than institutional incarceration and this type of approach may appear better than detention centers, but it is still a punitive sanction that fails to fully address the risks and needs of girls and their families," notes Laura Rubino, a Ph.D. candidate in criminal justice at UC, who coauthored the study. Instead, the study's authors call for programs for girls in the juvenile justice system that address social support, safety, and mental health.

The authors point to several limitations of their study, including shortcomings of the archival data (e.g., restricted flexibility in measurement, lack of measures of gender identity). In addition, racial/ethnic minority and LGBTQ+ girls are overrepresented in the legal system and consistently experience harsher treatment than their counterparts, which requires more research to understand the effects of in-home detention sanctions with diverse groups of youth.

HOUSTON - (June 21, 2021) - Rice University bioengineers collaborated on a six-year study that systematically analyzed how the surface architecture of breast implants influences the development of adverse effects, including an unusual type of lymphoma.

Every year, about 400,000 people receive silicone breast implants in the United States. According to FDA data, most of those implants need to be replaced within 10 years due to the buildup of scar tissue and other complications.

A team including researchers from the Massachusetts Institute of Technology (MIT), Rice, the University of Texas MD Anderson Cancer Center and Baylor College of Medicine published its findings online today in Nature Biomedical Engineering.

"The surface topography of an implant can drastically affect how the immune response perceives it, and this has important ramifications for the [implants'] design," said Omid Veiseh, an assistant professor of bioengineering at Rice who began the research six years ago during a postdoctoral fellowship at MIT. "We hope this paper provides a foundation for plastic surgeons to evaluate and better understand how implant choice can affect the patient experience."

The findings, were co-authored by two dozen researchers, including co-lead authors Veiseh and Joshua Doloff of Johns Hopkins University, MIT's Robert Langer and two of Veiseh's collaborators from the Texas Medical Center, Baylor's Courtney Hodges and MD Anderson's Mark Clemens.

Human impact

Veiseh, whose lab focuses on developing and studying biocompatible materials, said he is particularly excited about the discovery that surface architecture can be tuned to reduce host immune responses and fibrosis to breast implants.

"There's a lot we still don't understand about how the immune system orchestrates its response to implants, and it is really important to understand that within the context of biomaterials," Veiseh said.

Veiseh continued the research after joining Rice's faculty in 2017 as a CPRIT Scholar from the Cancer Prevention and Research Institute of Texas. He and two Ph.D. students from his lab, Amanda Nash and Samira Aghlara-Fotovat, collaborated on the project with the research groups of MD Anderson's Clemens and Baylor's Hodges to correlate findings from MIT animal studies with clinical data from human patients.

"Clinically, we have observed that patients exposed to textured-surface breast implants can develop breast implant-associated large cell lymphoma (BIA-ALCL), but this has not occurred with smooth-surface implants," said Clemens, an associate professor of plastic surgery at MD Anderson who leads a multidisciplinary treatment team on the disease. "This paper gives important novel insights into cancer pathogenesis with clear implications for preventing disease before it develops."

Veiseh said the work also provided important clues that will guide follow-up studies.

"That's the most exciting part of this: it could lead to safer, more compatible biomaterials and implant designs," Veiseh said.

Surface analysis

Silicone breast implants have been in use since the 1960s. The earliest versions had smooth surfaces, but patients with these implants often experienced a complication called capsular contracture, in which scar tissue formed around the implant and squeezed it, creating pain or discomfort as well as visible deformities. Implants could also flip after implantation, requiring surgical adjustment or removal.

In the late 1980s, some companies introduced rougher surfaces intended to reduce capsular contracture rates and make implants stay in place. The textured surfaces have peaks of varying heights. The peaks of some average hundreds of microns.

In 2019, the FDA requested breast implant manufacturer Allergan recall highly textured breast implants that had an average surface roughness of about 80 microns due to risk of BIA-ALCL, a cancer of the immune system.

In 2015, Veiseh and Doloff, then postdocs in the lab of MIT's Langer, began testing five commercially available implants with different surface designs to see how they would interact with surrounding tissue and the immune system. These included the highly textured one that had been previously recalled, one that was completely smooth and three that were somewhere in between.

Experimental results

In a study of rabbits, the researchers found tissue exposed to the more heavily textured implant surfaces showed signs of increased activity from macrophages -- immune cells that normally clear out foreign cells and debris.

All of the implants stimulated immune cells called T cells, but in different ways. The study found implants with rougher surfaces stimulated more pro-inflammatory T cell responses. Among the non-smooth implants, those with the smallest degree of roughness (4 microns) stimulated T cells that appeared to inhibit tissue inflammation.

The findings suggest that rougher implants rub against surrounding tissue and cause more irritation. This may explain why the rougher implants can lead to lymphoma: The hypothesis is that some of the texture sloughs off and gets trapped in nearby tissue, where it provokes chronic inflammation that can eventually lead to cancer.

The researchers also tested miniaturized versions of implants in mice. They manufactured these implants using the same techniques used to manufacture human-sized versions, and showed that more highly textured implants provoked more macrophage activity, more scar tissue formation and higher levels of inflammatory T cells. The researchers worked with the Hodges' lab at Baylor to perform single-cell RNA sequencing of immune cells from these tissues to uncover the specific signals that made the immune cells more inflammatory.

"The surface properties of the implants have profoundly different effects on key signals between immune cells that help recognize and respond to foreign materials," said Hodges, an assistant professor of molecular and cellular biology at Baylor. "The results show that the lightly textured surface avoided the strong negative cytokine immune response induced by the rough surface."

Toward safer implants

After their animal studies, the researchers examined how human patients respond to different types of silicone breast implants by collaborating with MD Anderson on the analysis of tissue samples from BIA-ALCL patients.

They found evidence of the same types of immune responses observed in the animal studies. For example, they observed that tissue samples from patients that had been host to highly textured implants for many years showed signs of a chronic, long-term immune response. They also found that scar tissue was thicker in patients who had more highly textured implants.

"Doing across-the-board comparisons in mice, rabbits and then in human [tissue samples] really provides a much more robust and substantial body of evidence about how these compare to one another," Veiseh said.

The authors said they hope their datasets will help other researchers optimize the design of silicone breast implants and other types of medical silicone implants for better safety.

"We are pleased that we were able to bring new materials science approaches to better understand issues of biocompatibility in the area of breast implants," said Langer, the study's senior author and MIT's David H. Koch Institute Professor. "We also hope the studies that we conducted will be broadly useful in understanding how to design safer and more effective implants of any type."

New York (June 21, 2021)--The American Geriatrics Society (AGS) has published an updated version of the AGS Minimum Geriatrics Competencies for Graduating Medical Students, which were created to ensure that medical school graduates across the U.S. are prepared to provide high-quality care for us all as we age. A refresh of the original set first published more than a decade ago, the 27 competencies integrate new concepts that have emerged more recently in the field of geriatrics, including frailty and person-centered care, and are framed around five key areas of focus for all geriatrics healthcare professionals.

"The updated competencies reflect an evolution in how we frame the work of geriatrics health professionals, a greater understanding of frailty, and a greater focus nationally on ensuring that care is person-centered and driven by individual goals," explained AGS President Peter Hollmann, MD, AGSF. "With these competencies, the field of geriatrics has defined not just what all physicians should know as they embark on their careers but also how they should put that knowledge into practice."

The updated AGS Minimum Geriatrics Competencies for Graduating Medical Students are organized around the Geriatrics 5Ms, a framework developed in 2017 by Frank Molnar, MD, Allen Huang, MD, AGSF, and Mary Tinetti, MD, AGSF, around five key areas: Mind, Mobility, Medications, Multicomplexity, and what Matters most. Clinical educators in medical schools are rapidly adopting the 5Ms as a framework for teaching medical students the skills, knowledge, and abilities they should have to provide high-quality clinical care for older adults. In the updated competencies set, each of the Ms contains new or modified competencies. Of particular note, multicomplexity, which describes the person who benefits most from geriatrics care, includes guidance on integrating a health equity lens into the practice of medicine.

"When we added a 27th competency, we believed it was critically important to highlight how important it is that physicians not only understand the impact that ageism and other forms of discrimination can have on the health of older adults but also take steps to overcome their own bias in addressing issues of health equity," AGS CEO Nancy E. Lundebjerg, MPA, said.

A workgroup of AGS leaders co-chaired by Rosanne Leipzig, MD, PhD, Andrea W. Schwartz, MD, and Mandi Sehgal, MD, updated the 26 original competencies using a modified Delphi method to reach a group consensus based on expert and stakeholder input and a literature review. Having presented their work at the 2021 AGS Virtual Annual Scientific Meeting, the team is currently working on a paper describing their methodology and key qualitative findings from their research. The updated competencies are now available on the AGS website here.

Moving forward, the AGS will continue to advocate that undergraduate medical education prepares graduating physicians to care for us all as we age. AGS is also developing educational tools to help educators to integrate attention to the new competencies into their programs.

WACO, Texas (June 21, 2021) - A new analysis of Venus' surface shows evidence of tectonic motion in the form of crustal blocks that have jostled against each other like broken chunks of pack ice. Published in the PNAS (Proceedings of the National Academy of Sciences), the study -- which includes contributions by Baylor University planetary physicist Peter James, Ph.D. -- found that the movement of these blocks could indicate that Venus is still geologically active and give scientists insight into both exoplanet tectonics and the earliest tectonic activity on Earth.

"We have identified a previously unrecognized pattern of tectonic deformation on Venus, one that is driven by interior motion just like on Earth," said Paul Byrne, Ph.D., associate professor of planetary science at North Carolina State University and lead and co-corresponding author of the work. "Although different from the tectonics we currently see on Earth, it is still evidence of interior motion being expressed at the planet's surface."

Venus had long been assumed to have an immobile solid outer shell, or lithosphere, just like Mars or Earth's moon. In contrast, Earth's lithosphere is broken into tectonic plates, which slide against, apart from, and underneath each other on top of a hot, weaker mantle layer.

James, an assistant professor of planetary geophysics and founder of Baylor University's Planetary Research Group, was part of the international group of researchers involved with the study. He has taken part in three NASA missions and specializes in using of spacecraft data to study the crusts and mantles of planets and moons.

"Earth is the only planet in the solar system with plate tectonics, so our planet is quite exceptional in that regard," James said. "That is particularly interesting when it comes to Venus: Why does a planet like Venus -- roughly the same size as Earth and made of the same types of rocks -- not behave the same way as Earth geologically?"

To answer that question, the team used radar images from NASA's Magellan mission to map the surface of Venus. In examining the extensive Venusian lowlands that make up most of the planet surface, they saw areas where large blocks of the lithosphere seem to have moved: pulling apart, pushing together, rotating and sliding past each other like broken pack ice over a frozen lake.

James provided calculations of the various mechanisms that could be responsible for the force driving the geologic activity on Venus. NASA's Magellan spacecraft measured the gravity field of Venus -- the subtle changes in the strength of gravity in different places on the planet. James was able to use this gravity field to demonstrate that viscous mantle flow, or slow churning, is strongly coupled to the crust.

"The mantle inside Venus pushes and pulls on the surface of the planet more strongly than Earth's mantle does. These calculations of the driving forces corroborated the discovery of block motion and helped us have a better understanding of how it works," James said.

The interior mantle flow found by the study's calculations is significant because it hasn't been demonstrated on a global scale previously. The movement of these crustal blocks could also indicate that Venus is still geologically active.

"We know that much of Venus has been volcanically resurfaced over time, so some parts of the planet might be really young, geologically speaking," Byrne said. "But several of the jostling blocks have formed in and deformed these young lava plains, which means that the lithosphere fragmented after those plains were laid down. This gives us reason to think that some of these blocks may have moved geologically very recently - perhaps even up to today."

The researchers are optimistic that Venus' newly recognized "pack ice" pattern could offer clues to understanding tectonic deformation on planets outside of our solar system, as well as on a much younger Earth.

"One of the neat things about planet research like this is that it helps us understand why our own planet works the way it does," James said. "The theme of our Planetary Research Group at Baylor is a quote from C.S. Lewis's Mere Christianity: 'Aim at heaven and you will get Earth thrown in.' That quote is intended in a spiritual context -- we should seek the kingdom of God before all else, and then this kingdom-mindset can even bear fruit in a secular sense. We like the double meaning of using space research to understand our own planet better."

Science related to Venus is especially timely -- NASA recently announced that it would be sending two new spacecrafts to Venus, VERITAS and DAVINCI+. These will be the first NASA missions launched to Venus since the 1980s. Additionally, the European Space Agency announced last week that it would be sending its own spacecraft called Envision to Venus.

"Strategically, this research is positioning Baylor to be involved with upcoming spacecraft missions. Venus is becoming a bigger priority for space agencies around the world, and we're plugged in to the exciting science opportunities that are on the horizon," James said.

Baylor will continue to be part of Venus research through James' lab. Rudger Dame, a Ph.D. candidate in James' lab, is focusing on Venus for his dissertation research. He has an internship this summer with the NASA Jet Propulsion Laboratory, under the advisement of Sue Smrekar, the principal investigator for the recently announced VERITAS spacecraft.

In addition, James is collaborating with NASA's Goddard Space Flight Center to study the planet Mercury's crust. He also led a recent study published in the journal Geophysical Research Letters about the discovery of a mysterious huge mass of material on the far side of the Moon -- beneath the largest crater in our solar system. The mass -- at least five times larger than the Big Island of Hawaii -- may contain metal from an asteroid that may have crashed into the Moon and formed the crater.

The South Pole-Aitken basin -- thought to have been created about 4 billion years ago -- is "one of the best natural laboratories for studying catastrophic impact events, an ancient process that shaped all of the rocky planets and moons we see today."

Women's electoral candidacies skyrocketed nationwide in the wake of the 2016 presidential election, which many saw as good news for democracy. But behavioral scholars have long maintained that women are more risk-averse than men, and thus are not as likely to sustain a prolonged political career -- involving election losses as well as wins -- the way men candidates traditionally have.

But behavioral scholars have long maintained that women are more risk-averse than men, and thus are not as likely to sustain a prolonged political career -- involving election losses as well as wins -- the way men candidates traditionally have.

Further, naysayers in a variety of media clips voiced that women were "sore losers," and they predicted that the surge of women entering politics at that time would have little long-term impact.

A new University of California, Davis, study suggests, however, that nationwide data show women are in politics for the long haul.

No 'flash in the pan'

"Contrary to those narratives, our results show that the surge in women candidates is unlikely to be a 'flash in the pan' for women's political representation," said Rachel Bernhard, co-author of the study and assistant professor of political science at UC Davis. "Far from being 'sore losers,' women who run for office are just as likely to persist as men."

Bernhard said the post-2016 surge has already created an increase in the base number of women candidates -- and therefore repeat candidates in the future -- such that women's representation in politics is unlikely to return to pre-2016 levels.

The paper, "Men and women candidates are similarly persistent after losing elections," was published today in the Proceedings of the National Academy of Sciences by Bernhard and co-author Justin de Benedictis-Kessner, a political scientist and an assistant professor of public policy at the Harvard Kennedy School.

Women not more likely to quit than men

Researchers analyzing 200,000-plus local and state candidates, running in more than 22,000 jurisdictions throughout the United States from 1950 to 2018, found that women who lose elections are no more likely to quit politics than men who lose. They argue that if women are more cautious and risk-averse, as researchers in economics, political science and social psychology have previously suggested, it is at the point they choose to either run for office or not -- not after a loss.

"Rather than rebutting previous theory, our results suggest a more nuanced theory of gender and political candidate persistence," researchers said in the paper.

Researchers also collected dozens of media clips from 2018, including from Fox News and the Christian Science Monitor, in which the recent surge in women candidates for office was seen by those commenting as temporary.

Election data was collected from a variety of sources, including California local races, and mayoral and state legislative races nationwide.

These are the arenas where most candidates begin their political careers, and where more women are likely to run for election. The elections researchers analyzed included school district, community college district, city and county elections as well as legislative elections.

"Unsurprisingly, those who win their races are much more likely to run for office in subsequent elections," researchers said in their paper. Among state legislative candidates throughout the country, winners are 51 percentage points more likely to run again than losers; among California local candidates, 18 percentage points; and among mayoral candidates nationwide, 47 percentage points.

In these data, propensity to run again after loss are similar for women candidates and men candidates, researchers found.

In analyzing the data, researchers found no statistically significant differences in candidates' responses to losing these races. In state legislative elections, for example, men who lose are 38 percentage points less likely to run again than when they win, while women are 39 percentage points less likely to run again. Overall, the effect of losing for first-time candidates is more likely to discourage them from running again than for experienced candidates, but again there were no distinguishable differences by gender.

"Once women overcome the barriers of running for office in the first place, they are just as likely to persist as men," Bernhard said.

"Since many women who ran in 2018 and 2020 will have to wait four years to run again, it's too soon for us to say exactly what the long-term effects of those surges were -- but based on the data we have, we are optimistic that many of those women are here to stay.

"We hope that these results will be encouraging for the people and organizations who are investing in women and working to get more women in office," she said. "While there is a lot of work to be done to get to gender equality in politics, this study shows that those investments aren't lost even when women lose elections."

The idea that a small number of "bad apples" are responsible for an outsized share of complaints against police officers has gained considerable traction over the last four decades. A new study considered the extent to which police misconduct is likely to be reduced by removing police officers identified early in their careers as being at risk for misconduct. The study concluded that replacing the top 10 percent of police identified as being the most likely to generate use-of-force complaints with officers who have not or are less likely to do so would reduce use-of-force complaints by just 6 percent over a 10 year period.

Conducted by researchers at the University of Pennsylvania and Princeton University, the study appears in Criminology & Public Policy, a publication of the American Society of Criminology.

"Our analysis suggests that removing predictably problematic police officers is unlikely to have a large impact on use-of-force citizen complaints," explains Aaron Chalfin, assistant professor of criminology at the University of Pennsylvania, who led the study. "Moreover, predicting who the problematic officers will be is difficult, so a better idea is to design early warning systems to deter problematic behavior and promote greater accountability."

Analyses of police departments across the United States suggest that a small share of officers accounts for a large share of complaints about misconduct against police. A common estimate is that the top 2 percent of officers account for about 50 percent of known misconduct. Such statistics suggest that reform efforts should focus on terminating the "bad apples" but, as the authors show, such a computation is misleading.

In this study, researchers used data from several sources, including: 1) citizen complaints that implicated Chicago police officers between 2012 and 2017 and 2) use-of-force data from the Chicago Police Department's tactical response reports from April 2011 to April 2016, focusing on the 11,283 officers employed by the department as of September 2017 and going back five years for each officer. The data were made available to the public by the Invisible Institute's Citizens Police Data Project, which hosts a collection of nearly 250,000 complaints against Chicago police officers filed since 1988. The study followed Chicago police officers hired between 2000 and 2007 for 10 years, ranking officers by the number of complaints they received early in their careers to predict future risk of having a complaint filed against them.

Researchers found that between September 2012 and September 2017, 2,885 complaints against Chicago police officers involved use of force. Looking backwards, the top 10 percent of officers accounted for 70 percent of the complaints, leading many observers to posit that the Chicago Police Department could appreciably reduce use-of-force complaints by removing a small number of "bad apples."

To determine whether this would be the most likely outcome, researchers carried out a policy simulation: First, they identified high-risk officers using information generated during their early-career 18-month probationary period, what the researchers termed an early warning system. Then they determined that there was considerable persistence in complaints over an officer's career, suggesting that, on average, officers identified as high risk early in their career persisted in being characterized as high risk later.

Next, the researchers simulated replacing the high-risk officers with officers less likely to have use-of-force complaints (using a variety of different configurations of officers) to estimate the share of citizen complaints over a 10-year period that would be abated solely by terminating officers at high risk of use-of-force complaints.

The study estimated that removing the top 10 percent of the police force (a very difficult task since current rates of termination are approximately 0.2 percent annually) with officers drawn from the middle of the distribution of officers would reduce total complaints just 4.6 percent and use-of-force complaints 6.1 percent. These estimates, which are rather small, reflect the difficulty of identifying "bad apples" early in officers' careers and suggest that a focus on computations that identify "bad apples" looking backwards (e.g., the top 10% of officers end up accounting for 70% of complaints) present a misleading view of the problem in policing.

The effects of terminating the top 10 percent of high-risk officers based on officers' rankings of likelihood using force during a five-year probationary period (instead of the 18-month probationary period) were larger, at 16 percent. But the authors caution that terminating such a large number of officers after five years of service would be politically challenging.

"Early warning systems that simply identify problematic officers and incapacitate them, either through termination or reassignment, are unlikely to lead to large reductions in the use of force," suggests Jacob Kaplan, a postdoctoral fellow at Princeton University, who coauthored the study. "But early warning systems that are coupled with rigorous oversight and genuine accountability might have a larger effect by generating deterrence or spillover effects among officers who are unlikely to be flagged as being high risk, or by changing departmental culture."

What is needed in police departments, the authors say, is broad-based measures to improve managerial practices and increase accountability. Toward this end, they suggest that policymakers provide incentives for better and more complete reporting and discovery of police misconduct.

Among the study's limitations, the authors note that while police departments' early warning systems are not a panacea, they could produce more changes in use-of-force complaints above and beyond the estimates of this study. In addition, they note that their simulation did not identify the promise of early warning systems more generally or what the effects might be at scale.

Furthermore, the authors note that in a city like Chicago, even a small proportional reduction in use-of-force complaints can translate into hundreds fewer complaints annually. This, in turn, could save millions of dollars in settlements of lawsuits as well as improve relations between police and the community.

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium present in many ecological niches, such as plant roots, stagnant water or even the pipes of our homes. Naturally very versatile, it can cause acute and chronic infections that are potentially fatal for people with weakened immune systems. The presence of P. aeruginosa in clinical settings, where it can colonise respirators and catheters, is a serious threat. In addition, its adaptability and resistance to many antibiotics make infections by P. aeruginosa increasingly difficult to treat. There is therefore an urgent need to develop new antibacterials. Scientists from the University of Geneva (UNIGE), Switzerland, have identified a previously unknown regulator of gene expression in this bacterium, the absence of which significantly reduces the infectious power of P. aeruginosa and its dangerous nature. These results, to be published in the journal Nucleic Acid Research, could constitute an innovative target in the fight against this pathogen.

RNA helicases perform essential regulatory functions by binding and unwinding various RNA molecules to perform their functions. RNA helicases are present in the genomes of almost all known living organisms, including bacteria, yeast, plants, and humans; however, they have acquired specific properties depending on the organism in which they are found. "Pseudomonas aeruginosa has an RNA helicase whose function was unknown, but which was found in other pathogens", explains Martina Valentini, a researcher leading this research in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine, and holder of an SNSF "Ambizione» grant. "We wanted to understand what its role was, in particular in relation to the pathogenesis of the bacteria and their environmental adaptation."

A severely reduced virulence

To do this, the Geneva team combined biochemical and molecular genetic approaches to determine the function of this protein. "In the absence of this RNA helicase, P. aeruginosa multiplies normally in vitro, both in a liquid medium and on a semi-solid medium at 37°C", reports Stéphane Hausmann, a researcher associate in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine and first author of this study. "To determine whether the infection capacity of the bacteria was affected, we had to observe it in vivo in a living organism."

The scientists then continued their research using Galleria mellonella larvae, a model insect for studying host-pathogen interactions. Indeed, the innate immune system of insects has important similarities with that of mammals. Moreover, these larvae can live at temperatures between 5°C and 45°C, which makes it possible to study bacterial growth at different temperatures, including that of the human body. Three groups of larvae were observed; the first, after injection of a saline solution, saw 100% of its population survive. In the presence of a normal strain of P. aeruginosa, less than 20% survived at 20 hours after infection. In contrast, when P. aeruginosa no longer possessed the RNA helicase gene, over 90% of the larvae remained alive. "The modified bacteria became almost harmless, while remaining very much alive," says Stéphane Hausmann.

Inhibiting without killing

The results of this work show that this regulator affects the production of several virulence factors in the bacteria. "In fact, this protein controls the degradation of numerous messenger RNAs coding for virulence factors", summarises Martina Valentini. "From an antimicrobial drug strategy point of view, switching off the pathogen's virulence factors rather than trying to eliminate the pathogen completely, means allowing the host immune system to naturally neutralise the bacterium and potentially reduces the risk for the development of resistance. Indeed, if we try to kill the bacteria at all costs, the bacteria will adapt to survive, which favours the appearance of resistant strains."

The Geneva team is currently continuing its work by screening a series of known drug molecules in order to determine whether any of them have the capacity to selectively block this protein, and to study in detail the inhibition mechanisms on which the development of an effective therapeutic strategy could be based.