Culture

Irvine, CA - April 14, 2021 - A new study, led by the University of California, Irvine (UCI), reveals how chronic inflammation promotes muscle fibrosis, which could inform the development of new therapies for patients suffering from Duchenne muscular dystrophy (DMD), a fatal muscle disease.

Titled, "A Stromal Progenitor and ILC2 Niche Promotes Muscle Eosinophilia and Fibrosis-Associated Gene Expression," the study was published today in Cell Reports.
Chronic inflammation is a major pathological process contributing to the progression and severity of several degenerative disorders, including Duchenne muscular dystrophy (DMD). Studies directed at establishing a causal link between muscular dystrophy and muscle inflammation have revealed a complex dysregulation of the immune response to muscle damage.

During muscular dystrophy, chronic activation of innate immunity causes scarring of skeletal muscle, or fibrosis, compromising motor function. How immunity is linked to the molecular and cellular regulation of muscle fibrosis was not well defined, until now.

"In our study we found the interaction between two types of cells--a novel stromal progenitor, which is similar to a stem cell, and group 2 innate lymphoid cells (ILC2), which are a type of immune cell that reside in skeletal muscle--promotes the invasion of white blood cells in muscle. This condition is associated with the elevation of genes that promote muscle tissue scarring found in DMD," said lead author Jenna Kastenschmidt, PhD, an assistant specialist in the UCI School of Medicine Department of Physiology & Biophysics.

The new study not only reveals the interaction of cells contributing to DMD, but it illuminates how muscle eosinophilia is regulated. Eosinophils are white blood cells that infiltrate dystrophic muscle causing fibrosis. In this study, researchers found that eosinophils were elevated in DMD muscle compared to control patients. In addition, researchers found the deletion of ILC2s in dystrophic mice mitigated muscle eosinophilia, reducing the expression of genes associated with muscle fibrosis. These findings contribute to the understanding of the complex regulation of muscle inflammation and fibrosis during muscular dystrophy.

"By further defining the interaction between skeletal muscle-resident immune and stromal cells, we can better understand how chronic inflammation promotes muscle fibrosis and, more importantly, we can facilitate development of novel therapies for DMD," said senior author Armando Villalta, PhD, assistant professor in UCI's Department of Physiology & Biophysics.

Ongoing work from Villalta's lab continues to focus on how distinct facets of the immune system regulate DMD pathogenesis and how these processes influence the efficacy and long-term stability of gene replacement therapy.

New research published in Science Advances provides a template for how to develop directly-acting antivirals with novel modes of action, that would combat COVID-19 by suppressing the SARS-CoV-2 viral infection. The study focused on the macrodomain part of the Nsp3 gene product that SARS-CoV-2 uses to suppress the host cell's natural antiviral response. This part of the virus's machinery, also known as Mac1, is essential for its reproduction: previous studies have shown that viruses that lack it cannot replicate in human cells, suggesting that blocking it with a drug would have the same effect.

The study involved a crystallographic fragment screen of the Nsp3 Mac1 protein by an open science collaboration between researchers from the University of Oxford, the XChem platform at Diamond Light Source, the UK's national synchrotron, and researchers from the QCRG Structural Biology Consortium at the University of California San Francisco. The international effort discovered 234 fragment compounds that directly bind to sites of interest on the surface of the protein, and map out chemical motifs and protein-compound interactions that researchers and pharmaceutical companies can draw on to design compounds that could be developed into antiviral drugs. This work is thus foundational for preparing for future pandemics.

"Robustly identifying this kind of chemical matter for promising and tractable targets like Nsp3 is a first step in rational drug discovery. This is always a long journey fraught with difficulty and failure, but the battery of new structural biology methods that we combined in this study, including fragment screening at Diamond and computational docking at UCSF, are helping to change drug discovery and make it easier to find effective drug candidates," comments Principal Beamline Scientist, Frank von Delft.

These fragments cover a wide range of chemical motifs, and the study lays out the next steps of designing more elaborate molecules that combine the observed themes, synthesizing them and confirming experimentally whether they strongly bind the protein and have a biological effect. The most promising compounds can then be progressed in fully-fledged drug discovery programmes, which includes not only improving the biological potency but also ensuring the final molecule has important drug properties such as easy absorption and minimal side effects.

Most drugs contain a few key components that cause the desired, effect while the rest of the molecule may be important for other reasons, such as solubility, uptake from the gut or how the drug is processed by our metabolism. Traditional high-throughput screening entails testing very large collections of bigger, generally sub-optimal molecules, which are experiment of great complexity.

Instead, fragment screening is an approach for identifying building blocks of the future drug molecule, observing how they interact with the protein under study, contextualizing those interactions, and providing starting points for molecules that directly influence the biology of the protein. This method significantly reduces the number of compounds that need to be screened to find one that really binds, while still informing a broad range of potential molecules. Doing the experiment by structural biology, as implemented at the XChem platform, yields this information directly in 3D, greatly accelerating up the design process and ensuring a far more cost-effective overall experiment.

The UCSF collaborators also used another innovative drug discovery technique, Computational Docking. This deploys computer models and simulations to assess the likely interactions of virtual molecules for favourable interactions with Mac1 and their promise as starting points for drug discovery. The team identified 60 candidates from a virtual library of 20 million molecules, which were then experimentally tested using X-ray crystallography, yielding 20 good hits.

"This is a significantly higher-than-random hit rate, validating the new specific docking methodologies developed by our UCSF colleagues. The high quality structural data of Mac1 that we obtained by X-ray crystallography was essential, but the validation of the approach means that in future, we have additional power for exploring compounds that are not physically available. Overall, this work not only accelerates our ability to validate whether targeting NSP3 Mac1 is an effective way to develop antivirals; it also is hugely valuable in improving the template of methodologies for future inhibitor discovery and development throughout the community of drug discovery," concludes Frank von Delft.

"Family clustering is a confirmed phenomenon associated with Covid-19, and harrowing stories of this disease ravaging families continue to be reported," a new article explains in the March-April issue of the Hastings Center Report. In one extreme example, 28 extended family members in California reportedly tested positive for Covid-19. Two of the family members who quarantined together required hospitalization, and one of them died from the infection. In family clustering cases, multiple loved ones may suffer from the symptoms of Covid-19 and be hospitalized, in quarantine, or recovering; and family members may also have died from the infection.

Family clustering can so devastate a family that there are no healthy, qualified surrogates available to support decision-making, or it can render the emotional burden of decision-making almost unbearable, as it must now be borne in near isolation. In "Navigating Ethical Challenges Posed by Family Clustering during the Covid-19 Pandemic," authors Nicole R. Van Buren, Elijah Weber, Mark J. Bliton, and Thomas V. Cunningham cite cases resulting in death, for instance, when a floor nurse unwittingly transmitted Covid-19 to her elderly father, when an urgent care physician unknowingly transmitted it to his elderly mother whom he lived with and cared for, and when an airport worker transmitted it to his wife, who in turn inadvertently transmitted it to her elderly father. In cases like these, the others observed family members experience guilt and shame, stemming from their belief that they caused their loved one's infection and death.

The authors provide several strategies for patients, doctors, nurses, and families to apply when confronting this phenomenon.

The March-April issue also examines the ethical challenges of consent in a pandemic in several essays, including a piece that looks at calls for prisoners to participate in research on vaccines for Covid-19, in part because the disease has hit prison populations particularly hard. Another essay examines informed consent at the intersection of clinical care and research.

The table of contents of the March-April Hastings Center Report is available here: https://onlinelibrary.wiley.com/toc/1552146x/2021/51/2

The slurred speech, poor coordination, and sedative effects of drinking too much alcohol may actually be caused by the breakdown of alcohol products produced in the brain, not in the liver as scientists currently think. That is the finding of a new study led by researchers from the University of Maryland School of Medicine (UMSOM) and the National Institute on Alcohol Abuse and Alcoholism. It was published recently in the journal Nature Metabolism and provides new insights into how alcohol may affect the brain and the potential for new treatments to treat alcohol misuse.

It is well known that the liver is the major organ that metabolizes alcohol, using the enzyme alcohol dehydrogenase to convert alcohol into a compound called acetaldehyde. Acetaldehyde, which has toxic effects, is quickly broken down into a more benign substance called acetate. This occurs through a different enzyme called acetaldehyde dehydrogenase 2 (ALDH2). Until now, alcohol and acetaldehyde, produced by the liver, have been considered important players in triggering the cognitive impairment associated with imbibing. Acetate, on the other hand, was considered relatively unimportant in producing effects like motor impairment, confusion, and slurred speech. Researchers also did not know which brain region or particular brain cells were most important for alcohol metabolism.

To learn more about the role played by the brain in alcohol metabolism, the researchers measured the distribution of ALDH2 enzyme in the cerebellum, using magnetic resonance (MR) scanners in both mice and in human tissue. They observed that ALDH2 was expressed in the cerebellum, in a type of nerve cell called an astrocyte, in both human brain tissue and in living mice.

The researchers found that this enzyme controlled the conversion of acetaldehyde into acetate in the brain. They also found alcohol-induced cellular and behavioral effects in specific regions of the brain where this enzyme was expressed. Acetate was found to interact with the brain messenger chemical called GABA, which is known to decrease activity in the nervous system. This decreased activity can lead to drowsiness, impair coordination, and lower normal feelings of inhibition.

"We found ALDH2 was expressed in cells known as astrocytes in the cerebellum, a brain region that controls balance and motor coordination," said Qi Cao, PhD, Assistant Professor of Diagnostic Radiology and Nuclear Medicine at the University of Maryland School of Medicine. "We also found that when ALDH2 was removed from these cells, the mice were resistant to motor impairment inducted by alcohol consumption."

Su Xu, PhDHe and his team also found the enzyme ALDH2 in other brain regions responsible for emotional regulation and decision-making (both impaired by excess alcohol consumption), including in the hippocampus, amydala, and prefrontal cortex.

These findings suggest that certain brain regions are important for alcohol metabolism and that abnormalities in the enzyme production in these brain regions can lead to detrimental effects associated with alcohol misuse. They also suggest that acetate produced in the brain and in the liver differ in their ability to affect motor and cognitive function.

"Our next step is to determine whether these mechanisms observed in mice also exist in people," said Dr. Cao. "We would like to know whether alcohol metabolism is directly regulated in the human brain. If further research confirms this to be the case, it could lead to potential new targets for treating alcohol use disorder.

Most people by now have memorized the public health guidelines meant to help minimize transmission of COVID-19: wash your hands, wear a mask, keep six feet apart from others. That part is easy.

What some may not realize is that upholding these guidelines in certain urban areas can present new challenges.

For example, how are you supposed to stay six feet apart from other people when the standard width of a sidewalk is only four feet? What do you do when you want to cross an intersection that requires pressing a button to activate the pedestrian signal, but you are avoiding touching any surfaces?

The COVID-19 pandemic has drastically altered the way individuals interact with other people and their environment, but some public health guidelines meant to protect people conflict with the way public spaces and transport in urban areas are built.

Drive, bike, or walk? The illusion of choice

Dr. David Rojas, an epidemiologist in the Department of Environmental and Radiological Health Sciences at Colorado State University, works with policy makers to improve urban design to make cities more inclusive and sustainable, resulting in better health outcomes for people.

In the case of COVID-19, he noticed that when urban areas were not optimized to accommodate mitigation strategies, it put some people in the awkward position of compromising certain public health guidelines to make a necessary trip to their place of work, school, or worship. Or fear of coming in contact with COVID-19 and the inability to safely travel outside the home kept other people inside.

"The decisions we make are dictated by the options we have. How we decide to move, for example, like whether we take a car or walk to work," Rojas said.

Choosing to travel by car may result in a shorter commute, but it can also mean less daily physical activity compared to bicycling or walking. Likewise, taking a bicycle on the road may get the muscles moving, but riding alongside vehicles every day increases exposure to air pollution from car exhaust.

"Some people don't have the time or opportunity to consider other options," Rojas said. "They have to take their kids to school and get to work within a short period of time, but public transportation is too slow or there aren't any bus stations nearby."

Try taking a bicycle to work when there aren't clearly marked bike lanes and traffic moves too quickly to ride safely. Or walking where the intersections and sidewalks are too narrow and the pedestrian crossings are dangerous.

The options available differ for everyone depending on a range of contributing factors, and any number of sustained detriments impact health, causing long-term issues like obesity, cardiovascular disease, or diabetes, among others. Even an increase of vehicles on the road raises the risk of traffic accidents, in turn putting pressure on the health care system that is responsible for treating resulting injuries.

Designing urban areas with everyone in mind leads to better health outcomes all the time, not only during a pandemic. But, when COVID-19 hit in 2020, people all over the world slowed down and cities adapted their mobility patterns and use of space. This shift created the perfect environment for Rojas to highlight opportunities for improvement in urban design geared toward improving health.

"We need to think about how people experience public spaces differently," Rojas said. "If we have better sidewalks, better connectivity, larger parks that are better designed for everyone, it will be good for chronic diseases, cancer, and many other relevant health outcomes."

10 interventions for long-term health

In an effort to help communities around the world adapt urban areas in light of COVID-19, Rojas worked with an urban planner to create an infographic that details 10 low-cost, temporary interventions to promote urban improvements and public health. The infographic not only identifies interventions that support COVID-19 mitigation strategies, but also explains that many of the changes can be made permanent to contribute to a long-term health vision.

Some of the interventions include adjusting traffic light timing to favor pedestrians and cyclists, expanding public open spaces, and concentrating freight traffic on main roads and at nighttime to improve traffic safety.

The tactical urbanism interventions as an expansion of short-term COVID-19 mitigation strategies are detailed in an article published in Current Environmental Health Reports.

With a projected two-thirds of the human population living in cities by 2050, Rojas asserts that urban designers should plan ahead in the interest of public health. Reponses to the COVID-19 pandemic could provide a push in the right direction.

"We can do two things: make the same mistake of 'copy and paste' regulations or make a change," Rojas said. "We can work with policy makers to not only impact how our cities are designed now, but also to implement better designs for cities created in the future."

To better understand how RNA in bacteria gives rise to protein--and along the way, target these processes in the design of new antibiotics--researchers are turning their attention to the unique way this process happens in bacteria.

In eukaryotic cells, transcription (the process by which information in a DNA strand is copied into messenger RNA) and translation (the process by which a protein is synthesized by the ribosome from the mRNA) are two successive steps. In bacteria, they occur simultaneously: As the RNA is being synthesized by RNA polymerase, the ribosome comes in to make the proteins.

This synchronicity allows for so-called "transcription-translation coupling," wherein the first ribosome can immediately follow and couple with the transcribing RNA polymerase. It is a new area of research that promises to bring insights into processes unique to bacteria that could be targeted with great specificity in the design of antibiotics.

Now, University of Michigan researchers have directly observed previously hidden RNA regulatory mechanisms within such couplings. The results, spearheaded jointly by postdoctoral fellows Surajit Chatterjee and Adrien Chauvier of the U-M Department of Chemistry and the U-M Center for RNA Biomedicine, are published in the Proceedings of the National Academy of Sciences.

The new results promise to have important implications for the future design of antibiotics that could target the coupling mechanism instead of targeting the transcription or translation processes separately.

"With RNA emerging as a major factor in our daily lives--note the SARS-CoV-2 viral genome and the mRNA vaccines to combat its replication--we are at a crossroads where the interplay between RNAs and proteins in their ubiquitous complexes becomes an attractive prospective target for the medicines of the future, including to fight drug-resistant bacterial strains," said senior author Nils Walter, professor of chemistry.

In particular, the researchers found that modulating the translation of a nascent mRNA affects the downstream synthesis of the mRNA itself. When translation is stopped or delayed, the transcription rate is slowed down to avoid overproduction of RNA that would only be degraded in the cell.

To conveniently modulate translation efficiency, the researchers exploited the features of a structured RNA, called a translational riboswitch, embedded near the start of an mRNA of the anthrax bacterium Bacillus anthracis. This RNA changes structure when binding a specific small ligand to reduce translation in response to environmental cues.

The current study shows that the riboswitch--generally thought to only affect translation--can in fact regulate both translation and transcription by exploiting their coupling. By using the riboswitch ligand to slow translation initiation, or inhibitors to delay or stop translation, the scientists observed effects also on the speed of RNA polymerase.

The authors expanded a combination of single-molecule fluorescence microscopy techniques to monitor the dynamic interactions of the transcription and translation machineries during different stages of coupling. They also developed a unique strategy to directly watch transcription-translation coupling in real-time, detecting that the small riboswitch controls the much larger transcription and translation machineries. The work thus surpasses and brings to life previous structure-based studies that provided only snapshots of the already coupled machineries.

The researchers say their results establish important foundations for future RNA research. They explain that the question of how other cellular factors contribute to establishing and maintaining transcription-translation coupling is still enigmatic, raising questions that remain to be investigated. This work could also bring insights into similar biological processes in other pathogenic organisms.

"It is fascinating to see how the huge transcription and translation machineries are held by a tiny mRNA for a controlled gene expression process in bacteria," said Chatterjee.

Chatterjee and Chauvier are senior postdoctoral fellows in the Walter lab within the U-M Department of Chemistry. They are interested in translational and transcriptional riboswitches, respectively. In this study, they combined their knowledge and interest for each aspect of the coupling.

"To me, it's not so much about bacteria, but rather about the biological processes of translation and transcription," Chauvier said. "Genetic regulation is a timely coordinated process and synchronization is the key for the bacteria to adapt to external threats."

Chatterjee, Chauvier and Walter were joined in the effort by graduate student Shiba Dandpat and collaborator Professor Irina Artsimovitch of Ohio State University.

"New evidence of the importance of the Roman/Byzantine Mons Smaragdus settlement within the emerald mining network"

A new paper published in the Journal of Near Eastern Studies presents the results of and images from the resuming of the archaeological seasons in the Mons Smaragdus region in the Egyptian Eastern Desert. The region is known for Roman-era emerald mines, chronicled by authors like Pliny the Elder and Claudius Ptolemy, were rediscovered in the 19th century by the French mineralogist Fréderic Cailliaud. During the 1990s a team from the "Berenike Project" started to survey the area and conducted the first excavations, focusing on the main site identified, Sikait, where the archaeological seasons resumed in January of 2018 and January 2020.

In "New evidence regarding emerald production in Roman Egypt coming from Wadi Sikait (Eastern Desert)" authors J. Oller Guzmán, D. Fernández Abella, V. Trevín Pita, O. Achon Casas, and S. García-Dils de la Vega detail what was found in three buildings. The first structure, referred to as the "Administrative building," was likely a temple long occupied between the 1st and the 4th-5th centuries. Nineteen coins were recovered at the site, along with other items indicating ritual use like incense burners and bronze and steatite figurines. The "Large Temple," one of the most well-preserved structures standing in Sikait, also contained religious artifacts like bones, terracotta body parts, and amulets, and was likely occupied between the 4th and the 5th centuries AD, although inner shrines were possibly used earlier, based on surviving traces of Egyptian hieroglyph and other materials. Finally, the "Six Windows Building" complex, possibly a residential space, included an older inner cavity, which may have been related to mining activity. However, concerning this type of structures, common in Sikait, the authors write, "After analyzing most of these spaces, we can conclude that almost none of them can be identified as beryl mines, and mainly we are dealing with storage or living spaces." Nevertheless, the study of the underground structures presents in Sikait and the surrounding areas allowed the documentation of several beryl mining spaces. The detailed analysis of some mines showed relevant evidence concerning their structure, typology, and evolution, including the discovery of the first register inscription ever found in an ancient emerald mine.

These excavation seasons, the authors write, add to knowledge about emerald production in Roman Egypt. "First, it confirmed the significance of the religious aspect in mining settlements like ancient Senskis." This shows the importance of the settlement within the emerald mining network, as there is no other site in which a similar concentration of cult spaces has been recorded. "This links Sikait to other productive regions in the Eastern Desert, which also offer plentiful evidence of the importance of cult and religion, like the imperial quarries."

The authors propose this work will provide key evidence in the future for determining how exactly were the mines exploited. Future seasons will focus on documenting the mining complexes to get a complete overview of the process of extraction and commercialization of emeralds, which will provide greater historical context. "According to literary sources such as Olympiodorus, in the 5th century AD a permit from the king of the Blemmyes was required to enter the emerald mines." Considering that most of the surviving structures in Sikait date to this period, archaeological information from such sites are fundamental for understanding the progressive abandonment of the Roman/Byzantine control in this area and the gradual substitution by the Blemmyan power.

The U.S. military veteran population is known to have abnormally high rates of suicide, so health officials have been concerned that the COVID-19 pandemic might elevate risk of psychiatric disorders, particularly among those suffering from post-traumatic stress and related disorders.

A recent national study of more than 3,000 veterans participating in the National Health and Resilience in Veterans Study did find that 12.8% reported post-traumatic stress disorder (PTSD) symptoms related to COVID-19 and 8% said they had contemplated suicide during the pandemic.

However, the same survey, published April 8 in JAMA Network Open, revealed another, startling finding. A full 43.3% of respondents -- more than three times the number of those reporting COVID-related PTSD symptoms and five times the number of those who had contemplated suicide -- said that they have experienced positive psychological benefits during the pandemic. These veterans reported greater appreciation of life, closer interpersonal relationships, and an increased sense of personal strength.

"Yes, there have certainly been many negative mental health consequences of the pandemic, but we are also seeing that a considerable proportion of people may experience positive psychological changes," said Robert Pietrzak, director of the Translational Psychiatric Epidemiology Laboratory of the U.S. Department of Veterans Affairs' National Center for PTSD, associate professor of psychiatry and public health at Yale, and lead author of the paper. "This suggests that the experience of stress and trauma related to the pandemic can lead to positive personal growth."

Over the past decade, Pietrzak and Steven Southwick, the Glenn H. Greenberg Professor Emeritus of Psychiatry at Yale and senior author of the new paper, have been studying veterans who experience what is known as "post-traumatic growth" following a traumatic experience. Scientists have long been fascinated with the concept of resilience -- how people who endure trauma find a way to bounce back. The concept of post-traumatic growth posits that while trauma can increase risk for mental disorders such as PTSD, it may also spur positive personal growth.

For the latest findings, Pietrzak and Southwick initially asked veterans about their psychological health between November of 2019 and March 2020. The advent of the pandemic motivated them to follow up that survey with another, of the same group, a year later. In this second survey, they asked questions about PTSD symptoms and possible positive psychological changes related to the pandemic.

Of the 3,078 veterans who responded to both surveys, 43.3% reported that the pandemic led to positive psychological changes in their lives. Among veterans who screened positive for COVID-related PTSD symptoms, more than 70% reported experiencing these changes.

"Post-traumatic growth is a process that often happens naturally and is stimulated by reflective processing about a traumatic event," Pietrzak said. "Sometimes you need to be sufficiently shaken by an experience and even experience symptoms of PTSD to begin to process it at a deeper level and ultimately be able to grow from it."

Greater post-traumatic growth -- particularly an increased appreciation of life and improved interpersonal relationships -- was also associated with a 40% lower likelihood of contemplating suicide during the pandemic. This finding suggests that psychological interventions to promote post-traumatic growth may be a helpful measure to prevent suicide among veterans.

While the scientific study of post-traumatic growth is relatively new, the concept is not. Ancient religious and spiritual traditions, philosophers, and scholars have long expressed the potentially transformative power of suffering.

"The saying 'Grow through what you go through' captures the essence of post-traumatic growth," Pietrzak said.

He and his colleagues plan to continue to follow their cohort of veterans over time to examine the longer-term course of post-traumatic growth and whether it may help promote resilience to subsequent traumatic events.

Biological energy flows, such as in photosynthesis and respiration, depend on the transfer of electrons from one molecule to another. Despite its importance to sustaining life, factors governing the rate of electron transfer, especially over long distances, are not well understood because the systems that mediate such ultrafast processes are very complex. A better understanding of electron transfer rates would help scientists improve chemical transformations, energy conversion, electronic devices, and photonic technologies.

Now, an international team of researchers led by UC Riverside has observed picosecond charge transfer mediated by hydrogen bonds in peptides. A picosecond is one trillionth of a second. As short-chain analogs of proteins, crucially important building blocks of living organisms, peptides are chains of chemically linked amino acids. The discovery shows the role of hydrogen bonds in electron transfer. The results are published in Proceedings of the National Academy of Sciences.

Valentine Vullev, a professor of bioengineering at UC Riverside's Marlan and Rosemary Bourns College of Engineering, along with Daniel Gryko from the Polish Academy of Sciences, and Harry Gray from the California Institute of Technology, led a team that discovered unusually ultrafast electron transfer from a donor to an acceptor molecule connected with oligopeptide linkers stretching up to 20 covalent bonds. Electron transfer usually takes a microsecond, or one millionth of a second, in peptides with such long through-bond distances.

The researchers were surprised to observe picosecond electron transfer, a rate 1 million times faster than previously known for such systems.

"It shouldn't work, but it does," Vullev said. "The picosecond charge transfer we observed contradicts structural biology, assuming the expected random distribution of structures of the flexible peptide chains."

The team chose donor and receptor molecules linked by short peptides they discovered actually assume well-defined structures stabilized by hydrogen bonds. Further analysis revealed that hydrogen bonds within each molecule brought the donor and acceptor close to each other in a scorpion-shaped molecular architecture, enabling picosecond electron transfer.

"This revolutionary design demonstrates short peptides can not only assume well-defined secondary conformations when templated by organic components but also provide a hydrogen-bonding network that can mediate electron transfer with unusually high efficiencies," Vullev said. "Our work provides unprecedented paradigms for the design and development of charge-transfer pathways along flexible bridges, as well as insights into structural motifs for mediating electron transfer in proteins."

The findings could lead to advances in energy storage as well as spur development of organic electronics that use conducting polymers instead of conducting minerals.

"One of the most exciting and fulfilling aspects about working in our group is being at the forefront of such discoveries and observing these spectacular results," said co-author John Clark, a doctoral student in Vullev's lab who did photochemical measurements for the research.

New research by University of Texas at Dallas scientists could help solve a major challenge in the deployment of certain COVID-19 vaccines worldwide -- the need for the vaccines to be kept at below-freezing temperatures during transport and storage.

In a study published online April 13 in Nature Communications, the researchers demonstrate a new, inexpensive technique that generates crystalline exoskeletons around delicate liposomes and other lipid nanoparticles and stabilizes them at room temperature for an extended period -- up to two months -- in their proof-of-concept experiments.

The Moderna and Pfizer/BioNTech COVID-19 vaccines use lipid nanoparticles -- basically spheres of fat molecules -- to protect and deliver the messenger RNA that generates a vaccine recipient's immune response to the SARS-CoV-2 virus.

"The expense of keeping these vaccines very cold from the time they're made to the time they're delivered is a challenge that needs to be addressed, especially because many countries don't have sufficient infrastructure to maintain this kind of cold chain," said Dr. Jeremiah Gassensmith, associate professor of chemistry and biochemistry and of bioengineering at UT Dallas and a corresponding author of the study. "Although we did not include in this work the specific lipid nanoparticles used in current COVID-19 vaccines, our findings are a step toward stabilizing a lipid nanoparticle in a way that's never been done before, so far as we know."

The idea for the research project began during a coffee-break discussion between Gassensmith and Dr. Gabriele Meloni, a corresponding co-author of the study and assistant professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics at UT Dallas.

Gassensmith's area of expertise is biomaterials and metal-organic frameworks, while Meloni's research focus is transmembrane transporter proteins. These proteins reside within cell membranes and are crucial for moving a variety of small molecules, including ions and trace metals, in and out of cells for several purposes.

"Membrane proteins sit in a cell membrane, which is a lipid bilayer," Meloni said. "To study their structure and biophysical and biochemical properties, we must extract these proteins from the membrane using detergents and then reconstitute them back into an artificial membrane -- a proteoliposome -- that mimics the proteins' natural environment."

Shell Creation

Lipid nanoparticles and liposomes are similar in structure, and neither are thermodynamically stable at room temperature, Gassensmith said. The lipid structures can fuse or aggregate, exposing any embedded membrane proteins or cargo to degradation.

"One of the challenges in my field of research is that both membrane proteins and lipid bilayers are very delicate and intrinsically metastable, and we're trying to combine them in order to understand how these proteins function," Meloni said. "We have to handle them carefully and prepare them fresh each time. They cannot be stored for long periods and are not easily shipped to colleagues in other labs."

The researchers joined forces to develop a methodology to stabilize this kind of lipid system and demonstrated their results using transmembrane proteins from Meloni's lab as a case study.

They mixed liposomes -- some with embedded proteins, some without -- with a combination of two inexpensive chemicals, zinc acetate and methylimidazole, in a buffer solution. In about a minute, a crystal matrix began to form around individual liposomes.

"We think that the lipids interact with the zinc just strongly enough to form an initial zinc-methylimidazole structure that then grows around the lipid sphere and completely envelops it, like an exoskeleton," Gassensmith said. "It's analogous to biomineralization, which is how certain animals form shells. We sort of co-opted nature in creating this totally fake shell, where the biomacromolecules -- the lipids and proteins -- catalyze the growth of this exoskeleton."

The ability of biomimetic shells to form around biological molecules is not new, Gassensmith said, but the process hasn't worked well with lipids or liposomes because the metal salts that comprise the shell material suck water out of the liposomes by osmosis and cause them to explode.

"One of the keys to this research was identifying the buffer solution in which everything resides," Gassensmith said.

Building a Buffer

Three graduate students collaborated on the project to develop the unique buffer medium that allows the reaction to occur.

"The buffer medium maintains the ionic strength of the solution and keeps the pH stable so that when you add a huge amount of metal salts, it doesn't osmotically shock the system," said Fabián Castro BS'18, a chemistry doctoral student in Gassensmith's lab and a lead author of the study.

Castro and co-lead authors Sameera Abeyrathna and Nisansala Abeyrathna, chemistry doctoral students (and siblings) in Meloni's lab, worked together to develop the buffer formulation.

Once the biomolecules have grown a shell, they are locked in, and the lipids remain stable. While the exoskeleton is very stable, it has a fortuitous Achilles' heel.

"The shell will dissolve if it encounters something that is attracted to zinc," Gassensmith said. "So, to release and reconstitute the liposomes, we used a zinc chelating factor called EDTA (ethylenediaminetetraacetic acid), which is a common, inexpensive food additive and medicine used to treat lead poisoning."

In addition to the laboratory experiments, in another proof-of concept exercise, Gassensmith mailed through the U.S. Postal Service a sample of the stabilized lipid particles to his mother in Rhode Island. She shipped them back to Texas, but because the COVID-19 pandemic forced the shutdown of most UT Dallas research labs in 2020, the samples sat untouched for about two months until the graduate students returned to campus to examine them. Although the informal experiment lasted much longer than the researchers had expected, the samples survived and functioned "just fine," Gassensmith said.

"This project required two different types of expertise -- my group's expertise in membrane transport proteins and Dr. Gassensmith's long track record working with metal-organic frameworks," Meloni said. "Our success clearly demonstrates how such collaborative research can bring about novel and useful results."

ITHACA, N.Y. - Women's increased agricultural labor during harvest season, in addition to domestic house care, often comes at the cost of their health, according to new research from the Tata-Cornell Institute for Agriculture and Nutrition (TCI).

Programs aimed at improving nutritional outcomes in rural India should account for the tradeoffs that women experience when their agricultural work increases, according to the study, "Seasonal time trade-offs and nutrition outcomes for women in agriculture: Evidence from rural India," which published in the journal Food Policy on March 24.

"To earn more income during peak seasons, landless women have no choice but to spend time in agricultural work, besides engaging in domestic work," said first author Vidya Vemireddy, a TCI alumna and assistant professor at the Indian Institute of Management Ahmedabad. "In contrast, women who have larger farms or higher incomes may choose to reduce the time they spend on agriculture and household activities via hired labor or labor-saving technologies."

To see how time constraints impact women's nutritional outcomes, Vemireddy and TCI director Prabhu Pingali surveyed 960 women from rural Maharashtra, India, about their time use and diets. Their work included an index of standardized local recipes to measure nutrient intake and cooking time.

Pingali is also a professor in the Charles H. Dyson School of Applied Economics and Management, with joint appointments in the Division of Nutritional Sciences and the Department of Global Development in the College of Agriculture and Life Sciences.

Women in rural India face severe constraints on time. They spend about 32% of their time on agricultural activities such as transplanting, weeding and harvesting, while also responsible for unpaid household labor like cooking, cleaning, fetching water and caring for children, Vemireddy and Pingali say. This workload increases during peak agricultural seasons, when they must spend up to five and a half hours per day sowing and harvesting.

Men, by comparison, face fewer time constraints since they spend very little time doing housework.

During peak agricultural seasons, the increased labor leaves women with less time for other personal activities. Vemireddy and Pingali found that these time trade-offs are associated with a decrease in caloric, protein, iron and zinc intake. More specifically, each 100-rupee increase in a woman's agricultural wages per day - meaning she spent more time working on the farm - is associated with a loss of 112.3 calories, 1.5 g of protein, 0.7 mg of iron and 0.4 mg of zinc.

This decrease is likely due to the women having less time and energy to cook nutritious meals, according to Pingali. "Most of the women we surveyed cooked two meals per day," Pingali said. "When faced with a longer workday on the farm, they might have less time to cook in the morning or be too tired in the evening, choosing instead to make easier, less time-consuming, and less nutritious dishes."

These nutritional deficits are worse for landless women who work on other people's farms, grow only food crops, or grow a mix of food and cash crops. By contrast, women who own large tracts of land and specialize in cash crops like cotton see little decline in nutrition during peak seasons, possibly because they have higher incomes.

The negative relationship between women's nutrition and increased farm work has important implications for development programs and interventions that seek to use agriculture to improve nutrition outcomes, such as encouraging households to grow kitchen gardens, the researchers said.

"Agricultural policies and programs that require greater involvement of women must recognize the consequences of increased time burdens and their adverse effects on nutrition," Vemireddy said. "The programs should be designed in such a way that the benefits of women's participation in agriculture outweigh the losses, such as time for well-being enhancing activities."

Vemireddy and Pingali said labor-saving strategies and technologies can lower the burdens placed on women by agricultural and household labor.

However, they said, managing time burdens alone can only improve nutrition so much. Successfully addressing malnutrition in India will still require a reorientation of the country's food policies to make nutrient-rich foods more accessible and affordable.

PHOENIX, Ariz. -- April 13, 2021 -- Findings of a study by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that increasing expression of a gene known as ABCC1 could not only reduce the deposition of a hard plaque in the brain that leads to Alzheimer's disease, but might also prevent or delay this memory-robbing disease from developing.

ABCC1, also known as MRP1, has previously been shown in laboratory models to remove a plaque-forming protein known as amyloid beta (Abeta) from specialized endothelial cells that surround and protect the brain and cerebral spinal cord. Building on previous studies, TGen conducted a series of pre-clinical genomic laboratory experiments. Results suggest that ABCC1 not only could export Abeta out of the brain, but that increasing the expression of ABCC1 could reduce Abeta production, thus preventing, or delaying, the onset of Alzheimer's.

The findings were published in the scientific journal Biology Open.

"Much work remains toward developing a drug that slows the development of or prevents Alzheimer's disease, but our findings suggest that targeting ABCC1 offers a promising path that could eventually lead to effective therapeutics," said Wayne Jepsen, a Postdoctoral Fellow in TGen's Neurogenomics Division, and the study's lead author.

Alzheimer's disease is the sixth leading cause of death in the U.S., annually killing more than 120,000 people. There is no treatment that can effectively prevent or slow this disease. An estimated 5.8 million Americans age 65 or older have Alzheimer's, and that number is expected to more than double over the next 30 years.

Symptoms of Alzheimer's include: memory loss; difficulty learning new things and problems coping with new situations; difficulty with language and problems with reading, writing and working with numbers; difficulty organizing thoughts and thinking logically; and a shortened attention span.

ABCC1 is an Alzheimer's drug target

TGen's study results suggest that ABCC1 is a valid drug target for Alzheimer's because of the multiple ways the gene influences Abeta; not only potentially exporting it from the brain, but also in the way it modulates cellular processes involving amyloid precursor protein (APP), which is abundant in the brain and can be cut up into smaller pieces via the alpha- or beta-secretase pathways.

The alpha-secretase pathway is associated with the development and protection of neurons, which are the functioning cells of the brain and central nervous system. The resulting soluble APP alpha peptide is also associated with memory formation and a process called synaptic plasticity, in which the synapses that connect neurons and allow them to communicate are able to change and adapt to new information.

The beta-secretase pathway leads to the formation of Abeta, a peptide that accumulates to form amyloid plaques, which along with neurofibrillary tangles are the two pathological hallmarks that define Alzheimer's. Scientists have hypothesized that decreasing Abeta production could slow the progression of Alzheimer's.

TGen's experiments indicated that: ABCC1 modulates APP processing away from the formation of amyloid; confirms previous reports that ABCC1 exports Abeta from the inside of cells to the outside of cells; and that thiethylperazine, a drug long used to ease nausea and vomiting, increases ABCC1 transport activity.

"Compounds that can dramatically increase ABCC1 transport activity, or that can increase ABCC1 expression, may prove to be viable drugs for the treatment or prevention of Alzheimer's disease by not only increasing clearance of Abeta from the brain, but also by reducing the amount of Abeta that is produced," said Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, and the study's senior author.

"Interestingly, due to the historical focus in cancer research on finding ABCC1 inhibiting drugs, we are betting that there are already drugs out there that are known to have an opposite ABCC1-activating effect, and our data suggest that such drugs should be examined for anti-Alzheimer's disease activity," Dr. Huentelman said.

Dr. Todd Levine, a neurologist at HonorHealth and an adjunct faculty member at TGen who has reviewed the study but is not an author, said he believes the focus on ABCC1 is a potentially important new avenue of Alzheimer's research: "While it is still early days, the authors of this study present a compelling case for further investigation of ABCC1 as a potential target for new therapeutics against this devastating disease for which better treatments are urgently needed."

In a new study, Dr. LU Xiankai and his colleagues from the South China Botanical Garden (SCBG) of the Chinese Academy of Sciences (CAS) found that tropical forests can capture carbon dioxide (CO2) into soils and thus reduce emitted CO2. But how exactly do tropical forest soils capture atmospheric CO2?

Current knowledge of forest soil carbon sequestration mainly focuses on temperate and boreal forests, where most ecosystems are nitrogen-limited, and an increase in nitrogen supply can enhance net primary productivity (NPP) and subsequent soil carbon sequestration.

Traditionally, many scientists thought that nitrogen-rich tropical forests are unlikely to increase belowground soil carbon storage under greater nitrogen supply due to a lack of stimulation of NPP. However, this assumption has not been fully verified under field conditions, and belowground ecosystems have always been neglected by scientists.

Dr. LU and his colleagues initiated more than a decade of continuous nitrogen addition experiments in a nitrogen-rich tropical forest ecosystem and quantitatively demonstrated that excessive nitrogen deposition significantly increased soil carbon storage by 7-21%.

According to the researchers, soil carbon sequestration efficiency was estimated to be 9 kg of carbon per unit of added nitrogen, which is comparable to temperate forest ecosystems. Interestingly, soil nitrogen retention was significantly and positively correlated with carbon sequestration.

Combining these field experiments with other global data, they concluded that nitrogen deposition stimulates soil carbon sequestration, which is prevalent throughout nitrogen-limited and nitrogen-rich ecosystems, however the underlying mechanisms of these two ecosystems are different.

In nitrogen-limited ecosystems, nitrogen deposition stimulates soil carbon sequestration of organic carbon by increasing aboveground plant litter inputs to forest soils and reducing CO2 emissions from soils. In nitrogen-rich forests, however, the subsequent decreases in CO2 emissions and dissolved organic carbon leaching from soils are the two major drivers of carbon sequestration.

The researchers showed that organic matter interacting with soil minerals plays the dominant role in regulating the stabilization of soil carbon stocks for the two ecosystems.

"This study for the first time proves that excess nitrogen deposition can promote soil organic carbon accumulation in nitrogen-rich tropical forests," said Dr. LU, the first author of the study and principal investigator of the Nitrogen Biogeochemistry Lab at SCBG. "We have highlighted that these mechanisms can be incorporated into state-of-the-art Earth models, improving prediction of terrestrial carbon cycles under global change scenarios."

"Our findings, however, do not imply that we encourage loosening limits on nitrogen emissions into the atmosphere, in view of their adverse impacts on the environment and human health," said LU.

A group of researchers from Kobe University and Chiba University has successfully developed a flexible and simple method of artificially producing genetic switches for yeast, a model eukaryotic organism. The group consisted of Researcher TOMINAGA Masahiro*1, Associate Professor ISHII Jun*2 and Professor KONDO Akihiko*3 (of Kobe University's Graduate School of Science, Technology and Innovation/Engineering Biology Research Center), and Professor UMENO Daisuke et al. (of Chiba University's Graduate School of Engineering).

Genetic switches are gene regulatory networks that control gene expression. The researchers established a platform for creating genetic switches that could be applied to the development of sophisticated, artificially controlled yeast cells to produce large quantities of valuable compounds. These research results were published in 'Nature Communications' on March 23, 2021.

*1 Technology Research Association of Highly Efficient Gene Design (TRAHED) researcher.
*2 Ibid. Vice Director of the Kobe Center.
*3 Ibid. Director of the Kobe Center.

Main Points

Genetic switches are necessary in order to artificially generate new functions in an organism. These switches control the amount of proteins produced by a gene (i.e. gene expression (*1)) and the timing of this production.

There has been a lag in the development of genetic switches for eukaryotic organisms in particular, as well as a significant limitation on the number of genes that can be controlled at the same time.

The researchers developed a new selection platform in which the cutoff threshold can be set. This enabled them to succeed in creating highly functional, artificial genetic switches for yeast that can be produced easily and flexibly.

The developed platform is expected to have a wide range of applications in situations that require precise control of expression levels and timing for a large number of genes. This includes optimizing the balance of metabolic enzyme expression in the construction of cells for producing useful substances that have complex intracellular metabolisms.

Research Background

The number and type of genes that an organism possesses do not solely determine its life functions. The timing and quantity of proteins produced by a gene (i.e. gene expression) are other factors that are known to result in significant alterations. In the field of synthetic biology, recent advances have made it possible to generate many novel cell functions by artificially controlling the expression of certain genes. Genetic switches are necessary in order to control the rate and timing of gene expression. A genetic switch (Figure 1) is a regulatory system that turns the expression of a particular gene 'on' or 'off' in response to a stimulus (or inducer) from either inside or outside the cell (for example, the presence of a chemical substance). Consequently, genetic switches are an essential tool for synthetic biology, which aims to artificially design and construct cellular functions.

Many genetic switches have been developed for simple, single cell organisms (prokaryotes) such as E. coli. However, the systems of gene expression in eukaryotic organisms, such as humans, plants and yeast, are more complex. Consequently, there is a lag in the development of genetic switches for these organisms. Even though yeast is a model eukaryotic organism, attempts to engineer the functions of its cells have faced great limitations.

Research Methodology

When constructing genetic switches, it is very difficult to predict where and how to alter the switches to enable gene expression to be controlled. Evolutionary molecular engineering is a useful method for determining this (Figure 2). The method involves creating a library of genetic switch variants by randomly inducing mutation (*2) in part of or the entire genetic switch, and then selecting the variants that show intended performance. Although it is easy to produce a large number of variants, the desired variants within this number must be quickly identified. An artificial process of elimination (selection) was carried out to select the cells that remained both when gene expression was 'off' and when gene expression was turned 'on' by a specific inducer. However, if the selection is too strong or too weak, it is not possible to single out the best variants. Although it is necessary to select functional genetic switch variants that are suitably robust in both 'on' and 'off' states, it is very difficult to predict how strong the selection should be beforehand.

The team of researchers from Kobe University and Chiba University established a workflow system whereby they could generate selections of varying strengths in parallel by changing the type or concentration of the chemicals used for selection. After selecting a group of variants, the researchers exposed each one to an external stimulus (inducer) and analyzed the extent to which this turned gene expression on by observing the change in the level of light emitted from GFPs (green fluorescent proteins). This allowed them to determine the most appropriate selection, in other words to easily identify genetic switch variants that demonstrated a high level of performance. Using this method, the researchers successfully developed three new genetic switches that were as efficient as the best-performing switch developed for yeast up until now.

By integrating these three genetic switches, the researchers produced yeast that could biosynthesize orange pigment (β-carotene) under AND-gated control (i.e. where β-carotene could only be produced if two specific chemical compounds, DAPG and HSL, were present) (Figure 3).

Further Developments

The selection method developed by this research group will expedite the development of a wide range of genetic switches for yeast, with various performance levels and characteristics. This will also lead to a rapid increase in the number of genes that can be controlled in parallel. Combining these new genetic switches will make it possible to artificially design cellular functions. For example, this could contribute towards the development of sophisticated, artificially regulated yeast cells for producing large quantities of useful organic compounds.

Glossary

1. Gene expression: Genes encode proteins and are made up of 4 types of bases: A, T, G and C. Proteins are produced according to the arrangement of these bases. This process is called gene expression.
2. Mutation: A change in the type of bases that make up a gene. Mutations alter the instructions for making proteins and can result in changes in protein function.

Acknowledgements

This research received funding from the following:

The Japan Agency for Medical Research and Development (AMED)'s 'Project Focused on Developing Key Technology for Discovering and Manufacturing Drugs for Next-Generation Treatment and Diagnosis' (grant numbers JP19ae0101055 and JP19ae0101060).

The New Energy and Industrial Technology Development Organization (NEDO)'s project for the 'Development of Production Techniques for Highly Functional Biomaterials Using Smart Cells of Plants and Other Organisms' (Project Number P16009).

The Japan Science and Technology Agency's JST-Mirai Program (grant number JPMJMI17EJ).

A Grant-in-Aid for Scientific Research on Innovative Areas from the Japan Society for the Promotion of Science (JSPS) in the project area entitled 'Creation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries' (JP16H06450)

JSPS KAKENHI grants (numbers JP18K14374, JP15H04189 and JP15K14228).

Journal Information

Title:
"Robust and flexible platform for directed evolution of yeast genetic switches"
DOI: 10.1038/s41467-021-22134-y

Authors:
Masahiro Tominaga, Kenta Nozaki, Daisuke Umeno, Jun Ishii, Akihiko Kondo.

Journal:
Nature Communications

Though noise may change moment by moment for humans, it has a more lasting effect on trees and plants.

A new Cal Poly study reveals that human noise pollution affects the diversity of plant life in an ecosystem even after the noise has been removed. This is the first study that explores the long-term effects of noise on plant communities. It was published in the Proceedings of the Royal Society B.

In a study conducted twelve years ago near natural gas wells in New Mexico, researchers found that there were 75% fewer piñon pine seedlings in noisy sites as in quiet ones. This was most likely due to the noise driving away the Woodhouse's scrub jay, which plants thousands of pine seeds while storing them to eat during the winter months.

A research team recently returned to the sites to find out whether the piñon pine had recovered over time.

Because companies change the sites where they use noisy compressors to help produce natural gas, some of the previously noisy sites had become quiet. In these areas, there were fewer seedlings and saplings compared to sites that didn't have compressors added to the wellpad to speed up gas extraction. The decrease in saplings results from the time when the site was noisy, but the decrease in seedlings shows that piñon pine seeds still weren't sprouting once the noise was removed.

"The effects of human noise pollution are growing into the structure of these woodland communities," said biology professor and senior author Clint Francis. "What we're seeing is that removal of the noise doesn't necessarily immediately result in a recovery of ecological function."

While it's possible that the piñon pine has decreased because of a lack of opportunities to produce, it's more likely that the Woodhouse's scrub jay hasn't returned to the formerly noisy area and so isn't planting seeds.

"Some animals, like scrub-jays, have episodic memory," said Jennifer Phillips, the lead author who worked on the project while a postdoc at Cal Poly and who is now a professor teaches at Texas A&M-San Antonio. "Animals like the scrub-jay that are sensitive to noise learn to avoid particular areas. It may take time for animals to rediscover these previously noisy areas, and we don't know how long that might take."

Researchers also found differences in juniper seedlings and communities of flowering plants depending on current noise levels and whether noise levels had recently changed because noisy compressors were moved. Sites with greater noise had fewer juniper seedlings and different types of plants than quiet sites. Because of the complexity of ecosystems, the cause of these changes is still unknown.

"Our results reveal that plant communities change in lots of ways with noise exposure," Francis said. "We have a decent understanding of how and why foundational trees like piñon pine are affected by noise from our previous work with jays, but we are also seeing large changes in plant communities through changes in the abundance of shrubs and annual plants. These changes likely reflect impacts of noise on animals that eat plants, such as deer, elk and various insects, plus the many pollinators that are important for plant reproduction. In essence our research indicates that the consequences of noise are far-reaching and reverberate throughout the ecosystem through lots of species."

Future studies can offer a more fine-tuned look at how noise is causing these ecosystem changes. Researchers want to know more about which herbivores, seed dispersers and pollinators avoid or are attracted to noise and how changes in insect and animal behavior combine to affect plant communities.

Based on patterns from over a decade of an ecosystem experiencing noise pollution, evidence suggests that plant communities may take a long time to recover from the effects of human noise. Still, co-author and lead botanist Sarah Termondt, a Cal Poly research affiliate, emphasizes the need to understand the full and lasting costs of noise. "Continuing to look at long-term changes in floristic inventories over time will elucidate whether communities do eventually recover after long periods of noise pollution, even once it is removed from the landscape," she said.

When changes to plant communities are viewed alongside the growing evidence for the problems that noise creates for animals, it is increasingly difficult to ignore the near absence of noise regulations across the U.S.