Culture

At the beginning of the COVID-19 pandemic, intense social distancing and lockdown measures were the primary weapon in the fight against the spread of SARS-CoV-2, but they came with a monumental societal burden. New research from the Center for the Ecology of Infectious Diseases and the College of Public Health at the University of Georgia explores if there could have been a better way.

Published in the journal Proceedings of the Royal Society B, the research analyzes more palatable alternatives to the kind of social distancing mandates that threw a wrench at how businesses, schools and even family gatherings work. The alternatives--widespread testing, contact tracing, quarantines, certification for non-infected people and other public health policy measures--can slow the spread when combined together, but only with significant investments and broad public compliance.

"I understand why government leaders quickly enacted strict social distancing mandates as the COVID-19 pandemic was rapidly spreading in 2020," said lead author John Drake, director of the Center for the Ecology of Infectious Diseases and Distinguished Research Professor in the Odum School of Ecology. "This was the best that we could do at the time. However, school and workplace closures, gathering limits and shelter-in-place orders have had extreme economic consequences. These are harsh, and we really need to find alternative solutions."

Drake worked with other researchers to develop two models. One targeted how to find infected people to limit transmission through active case finding (through testing of at-risk individuals), thorough contact tracing when cases arise, and quarantines for people infected and their traced contacts.

The second model focused on a strategy of limiting exposure by certifying healthy individuals.

"Each model was tested independently and in combination with general non-pharmaceutical interventions (NPIs)," said co-author Kyle Dahlin, a postdoctoral associate with the center.

For this study, those interventions were defined as behavioral or generalized interventions that can be broadly adopted, such as wearing a face mask, hand washing, enhanced sick leave, micro distancing and contactless transactions.

"When we ran the model to evaluate the effectiveness of only using social distancing measures, like workplace closures, after the onset of the first wave, approximately half of the population eventually became infected," said study co-author Andreas Handel, associate professor of biostatistics and epidemiology in UGA's College of Public Health who helped design the models. "When we combined social distancing with general interventions, SARS-CoV-2 transmission was slowed, but not enough for complete suppression."

When they tested the model that actively looked for infection, they found that active case-finding had to identify approximately 95% of infected persons to stop viral spread. When combined with NPIs, like face masks, the fraction of active cases that needed to be located dropped to 80%. Considering that during the first wave of the pandemic in 2020, only 1% to 10% of positive cases were found, such an approach by itself wouldn't work.

The researchers also determined that adding contact tracing and quarantine to active case finding and general NPIs did not drastically change the model's success.

The model that targeted healthy people to limit exposure determined that to successfully control viral spread, SARS-CoV-2 test validity had to occur within a very narrow window of seven to 10 days with a waiting time of three days or less, and NPIs had to be strictly adopted. Otherwise, a large outbreak would occur.

Pej Rohani, Regents' and Georgia Athletic Association Professor of Ecology and Infectious Diseases in the Odum School and College of Veterinary Medicine, said that the models' conclusions indicated the need for continued research.

"These models are important because infectious disease ecologists and epidemiologists need to understand how SARS-CoV-2 transmission can be reduced using measures that do not have extreme societal consequences," he said.

The CEID's research highlighted the importance of a robust and widespread testing program, the general adoption of NPIs like face masks, and targeted measures to globally control the ongoing pandemic. These approaches are still extremely important as vaccines continue to be distributed.

A study published in July 2020 hypothesized a link between the presence of bradykinin, a well-known peptide, and severe cases of COVID-19. Vardan Karamyan, Ph.D., an associate professor and vice chair for the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy Department of Pharmaceutical Sciences, had not previously conducted or evaluated any research related to COVID-19. However, he found the article intriguing because it discussed bradykinin, one of three specific peptides with which his lab has much well-published experience.

The paper received a lot of attention in both the media and scientific literature, but as Karamyan read through it, he felt it failed to address an equally important part of a bigger picture: the likely involvement of two other bioactive peptides, known as substance P and neurotensin, in the same processes and mechanisms proposed by the authors.

"I decided to write a focused review article on the topic and looked for journals which announced special issues devoted to COVID-19," Karamyan recalled.

Karamyan learned that the American Physiological Society (APS) had two journals with ongoing special issues focusing on COVID-19. Because APS has a membership base of highly accomplished scientists and a wide audience, Karamyan submitted the manuscript of his focused review to Physiological Reports, one of APS's peer-reviewed journals that published Karamyan's review in its March 2021 issue.

In the original article, which included the author's data and additional information from other research, Karamyan saw that the researchers had postulated that bradykinin was the peptide at the center of many of the complications experienced by patients with severe COVID-19 cases. Peptides are short chains composed of at least two and no more than 50 amino acids, which also are the building blocks of proteins.

"What they were saying makes sense, and it is really beautifully done; they branch out quite a bit and they put things together in a very systematic way," Karamyan explained. "But what was very surprising is that if their proposed mechanism was true, then two other peptides (substance P and neurotensin) should also be next to bradykinin; yet there was not even a single word about those two peptides."

Karamyan said it was obvious the original study arrived at some important findings, but he also knew that a basic tenant of science says the better any disease is understood, the better the chances of curing or managing it.

"That was their motivation too," Karamyan asserted. "Their study tells us, 'Look, maybe this is what is happening,' and that made me think that I really need to try to bring awareness that there are these two other peptides that could be equally important."

Almost since the pandemic began, research has shown that many of the worst cases of COVID-19 are related to cytokine storms, which is when the body overproduces cytokines in an effort to fight the virus. Cytokines are substances such as proteins, peptides or glycoproteins that are released by cells within the immune system to affect other cells. For instance, cytokines help the body manage conditions such as immunity, inflammation and hematopoiesis (the production of blood cells and platelets). When they are overproduced, however, the resulting cytokine storm can have deleterious effects.

"In the beginning, it's a compensatory reaction when the cytokines are produced, but when it is overdone, this makes things much worse," Karamyan added.

Using their own data and that put forward by previous investigators, the researchers who authored the original paper concluded it was the overexpression of bradykinin, or a bradykinin storm rather than a cytokine storm that was adversely affecting COVID-19 patients.

"As I noted, it makes sense," Karamyan said. "It's not that cytokines don't do anything, but I agree with them that bradykinin could make things worse."

To make their case, the authors of the original paper showed there were mechanisms that would make bradykinin appear to be upregulated, or increased within the body, while other mechanisms meant to degrade bradykinin are downregulated, or decreased. Karamyan said those same mechanisms also would affect substance P and neurotensin in the same manner at least 80% of the time.

"Those same mechanisms, or the majority of them, would lead to elevated levels of not just bradykinin, but also substance P and neurotensin," Karamyan said. "That's one fact; the second is that if this inflammation is going on, if things are deteriorating in a COVID-19 patient, in the same way that bradykinin is making things worse, these peptides are known to do the same thing, and the number one thing is where the vasculature becomes leaky and we have edema formation and so on."

Karamyan said the third fact he pointed out in his review is from his own collaborative and preliminary study with TTUHSC colleague Abraham Al-Ahmad, Ph.D., where they showed that these three peptides together -- bradykinin, substance P and neurotensin -- make more profound changes in vascular permeability than each of them produce alone. Vascular permeability refers to a blood vessel wall's capacity to allow other molecules and cells to pass through.

"When they're together, bradykinin, substance P and neurotensin kind of have this synergetic or combined effect," Karamyan said.

If those three peptides are concurrently available, Karamyan continued, they could adversely affect COVID-19 patients and lead to some of the conditions the authors mentioned such as vascular permeability, oxidative stress, inflammation, edema and others. He coined the term "vasoactive peptide storm" to describe the process.

"It's a made-up term, yes, but all three are vasoactive peptides that would do similar things," Karamyan said. "That's why I suggested a vasoactive peptide storm."

In the original paper, the authors proposed using drugs known as receptor blockers that can prevent or reduce the impact of bradykinin. Karamyan agreed, but suggested adding receptor blockers for substance P and neurotensin to yield better results. In fact, Karamyan's lab may already have an enzyme that can inactivate all three, though he said the approach is speculative at this point.

"An enzyme that we are working with called neurolysin actually degrades all three peptides," Karamyan said. "It inactivates bradykinin, neurotensin and substance P. An alternative approach -- again highly speculative -- could perhaps be instead of using three different drugs to block all three peptides, possibly using one enzyme to get rid of all three peptides."

Whether Karamyan decides to investigate the significance and impact of the so-called vasoactive peptide storm, or leave it for others more accustomed to working with COVID-19, Karamyan believes he may have found another piece to the pandemic puzzle. He and several colleagues have discussed testing the ability of neurolysin to deactivate all three peptides.

"These reviewers were telling me this is something that makes sense and is worthy of trying experimentally," Karamyan said. "Obviously, it was very pleasant to hear this and it gave me confidence. Since then, I'm kind of on the border. It would be some deviation from what I do in regards to the disease itself. In regards to the mechanisms, no, because this is my field: peptides and enzymes. As of now I don't have anything planned yet, but it is possible that I may, or we may collectively as a group look into it."

PITTSBURGH, May 5, 2021 - Subtle differences in the shape of the brain that are present in adolescence are associated with the development of psychosis, according to an international team led by neuroscientists at the University of Pittsburgh School of Medicine and Maastricht University in the Netherlands.

In results published today in JAMA Psychiatry, the differences are too subtle to detect in an individual or use for diagnostic purposes. But the findings could contribute to ongoing efforts to develop a cumulative risk score for psychosis that would allow for earlier detection and treatment, as well as targeted therapies. The discovery was made with the largest-ever pooling of brain scans in children and young adults determined by psychiatric assessment to be at high risk of developing psychosis.

"These results were, in a sense, sobering," said Maria Jalbrzikowski, Ph.D., assistant professor of psychiatry at Pitt. "On the one hand, our data set includes 600% more high-risk youth who developed psychosis than any existing study, allowing us to see statistically significant results in brain structure. But the variance between whether or not a high-risk youth develops psychosis is so small that it would be impossible to see a difference at the individual level. More work is needed for our findings to be translated into clinical care."

Psychosis is an umbrella term for a constellation of severe mental disorders that cause people to have difficulty determining what is real and what is not. Most often, individuals have hallucinations where they see or hear things that others do not. They also may have strongly held beliefs, or delusions, even when most people do not believe them. Schizophrenia is only one disorder associated with psychosis, and psychotic symptoms can occur in other psychiatric disorders, such as bipolar disorder, depression, body dysmorphic disorder or post-traumatic stress disorder. In people who receive a diagnosis of psychosis, there is a great deal of heterogeneity in outcomes over time.

Diagnosis usually happens in later adolescence and early adulthood, but most often symptoms begin to manifest in the teen years, when clinicians can use psychological assessments to determine a person's risk of developing full-blown psychosis.

Jalbrzikowsi and Dennis Hernaus, Ph.D., assistant professor in the School of Mental Health and Neuroscience at Maastricht University, are co-chairs of the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. This group pooled structural magnetic resonance imaging (MRI) scans from 3,169 volunteer participants at an average age of 21 who were recruited at 31 different institutions. About half--1,792 of the participants--had been determined to be at "clinical high risk for developing psychosis." Of those high-risk participants, 253 went on to develop psychosis within two years. The co-chairs emphasized that this study would not be possible without the collaborative efforts of the 100-plus researchers involved.

When looking at all the scans together, the team found that those at high risk for psychosis had widespread lower cortical thickness, a measure of the thickness of the brain's gray matter. In high-risk youth who later developed psychosis, a thinner cortex was most pronounced in several temporal and frontal regions.

Everyone goes through a cortical thinning process as they develop into an adult, but the team found that in younger participants between 12 and 16 years old who developed psychosis the thinning was already present. These high-risk youth who developed psychosis also progressed at a slower rate than in the control group.

"We don't yet know exactly what this means, but adolescence is a critical time in a child's life--it's a time of opportunity to take risks and explore, but also a period of vulnerability," Jalbrzikowski said. "We could be seeing the result of something that happened even earlier in brain development but only begins to influence behavior during this developmental stage."

Hernaus stressed that these findings underscore the importance of early detection and intervention in people who show risk factors for developing psychosis, which include hearing whispers from voices that aren't there and a family history of psychosis.

"Until now, researchers have primarily studied how the brains of people with clinical high risk for psychosis differ at a given point in time," Hernaus said. "An important next step is to better understand brain changes over time, which could provide new clues on underlying mechanisms relevant to psychosis."

Besides being underweight, babies born to women whose diet lacked sufficient protein during pregnancy tend to have kidney problems resulting from alterations that occurred while their organs were forming during the embryonic stage of their development.

In a study published in PLOS ONE, researchers affiliated with the University of Campinas (UNICAMP) in the state of São Paulo, Brazil, discovered the cause of the problem at the molecular level and its link to epigenetic phenomena (changes in gene expression due to environmental factors such as stress, exposure to toxins or malnutrition, among others).

According to the authors, between 10% and 13% of the world population suffer from chronic kidney disease, a gradual irreversible loss of renal function that is associated with high blood pressure and cardiovascular disorder.

The study, conducted at the Obesity and Comorbidities Research Center (OCRC), resulted from PhD research by first author Letícia de Barros Sene with a fellowship from FAPESP.

OCRC is a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP.

In the article, the researchers describe the molecular pathways involved in the proliferation and differentiation of embryonic and fetal kidney cells. They obtained this knowledge by sequencing microRNAs (often called miRNAs) from the offspring of rats fed a low-protein diet while gestating. MirRNAs are small non-coding RNAs that regulate gene expression.

“We know low-protein intake during pregnancy tends to lead to a 28% decrease in the number of the offspring’s nephrons, the structures that filter blood in the kidneys. The resulting overloading of nephrons has several consequences. In the case of rats, pups become hypertensive only ten weeks after birth, when they are still considered young,” Patrícia Aline Boer, a member of the OCRC team and last author of the article, told Agência FAPESP. A healthy kidney has about a million nephrons.

Fetal programming

There has been a great deal of research in recent decades on the links between maternal health during pregnancy and child development, especially focusing on a field known as developmental origins of health and disease (DOHaD).

“In humans, these links were first observed after World War Two as a result of what’s known as the ‘Dutch famine’ [Hongerwinter], when the Nazis blocked food supplies to the Netherlands. Scientific studies showed that babies born to women who starved while pregnant in this period were underweight and developed high blood pressure, alterations in response to stress, heart problems, propensity to diabetes, and increased insulin resistance,” said Boer, who is president of DOHaD Brazil.

Since then, this epigenetic phenomenon has been studied in greater depth using animal experiment models. To understand at the molecular level what triggered the reduction in the number of nephrons, the OCRC researchers analyzed expression of miRNAs and target genes in fetal kidneys (metanephros) of rats at 17 days of gestation.

“We know the drop in the number of nephrons isn’t a genetic but an epigenetic effect,” Boer said. “It’s caused by something in the environment. In this case, gene expression is altered by the stress of hypoproteinemia. The DNA sequence doesn’t change. The expression of some genes in the offspring is altered, and the alteration can be heritable – it can be transmitted to future generations. We studied mirRNAs because they’re very important to genetic expression and alterations not associated with changes in DNA.”

Compared analysis between rats fed a regular protein diet (17% of daily calorie intake) and a second group fed a low-protein diet (6%) during pregnancy revealed alterations in 44 miRNAs – seven of which in genes associated with the proliferation and differentiation of cells essential to nephron development, researchers found. Genetic sequencing, immunohistochemistry and morphological analysis demonstrated that maternal protein restriction changed the expression of miRNAs and proteins involved in renal development as early as the 17th day of gestation.

“Previous research showed a 28% reduction in nephrogenesis, and in our study, there was a 28% decrease in the cells that give rise to nephrons. The proportion was the same, which means there must be some kind of signaling during the embryonic period that the organ has to adapt to a low-protein intake,” Boer said.

Other examples of fetal adaptation to malnutrition leading to alterations in organ development can be found in nature, Boer explained. “In our study, we observed that stem cells [which will become nephrons] differentiate very rapidly and that there was more differentiation and less proliferation of the cells that form nephrons,” she said.

The article “Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus” (doi: 10.1371/journal.pone.0246289) by Letícia de Barros Sene, Wellerson Rodrigo Scarano, Adriana Zapparoli, José Antônio Rocha Gontijo and Patrícia Aline Boer is at: journals.plos.org/plosone/article?id=10.1371/journal.pone.0246289.

Journal

PLoS ONE

DOI

10.1371/journal.pone.0246289

Researchers from the University of Liverpool have shown the potential of repurposing an existing and cheap drug into a long-acting injectable therapy that could be used to treat Covid-19.

In a paper published in the journal Nanoscale, researchers from the University's Centre of Excellence for Long-acting Therapeutics (CELT) demonstrate the nanoparticle formulation of niclosamide, a highly insoluble drug compound, as a scalable long-acting injectable antiviral candidate.

The team started repurposing and reformulating identified drug compounds with the potential for COVID-19 therapy candidates within weeks of the first lockdown. Niclosamide is just one of the drug compounds identified and has been shown to be highly effective against SARS-CoV-2 in a number of laboratory studies.

Using their expertise in the fields of materials chemistry, long-acting drug delivery and pharmacology, CELT scientists used nanoprecipitation to form redispersible solid drug nanoparticle formulations of niclosamide that can be stored as solids, reconstituted with water and utilised as long acting injectables. Their research has demonstrated sustained circulating drug concentrations may be maintained for the duration of early infection after a single injection.

CELT is co-directed by pharmacologist Professor Andrew Owen and materials chemist Professor Steve Rannard at the University of Liverpool.

Professor Steve Rannard said: "Repurposing drug compounds is much more than using existing medicines for a new disease. The existing active drug compound needs to be shown to be active at a significant level, then reformulated to address new challenges. The conventional route of administration may also not be relevant and modifying the way the patient receives the drug compound is highly critical to efficacy. Niclosamide is an ideal candidate to be taken forward as a potential long acting injectable therapeutic to treat Covid-19.

"This is still in early-stage development but the CELT team are currently working with a contract manufacturing organisation to take this forward towards scale up and clinical manufacture. This work is progressing well and if successful, human trials would be next. We envisage a future `Test-and-Treat' scenario where infected people are treated at the point of diagnosis with the full course of therapy in one injection."

Professor Andrew Owen said: "Repurposing of medicines for SARS-CoV-2 has yielded mixed results, with some clear successes for immunomodulatory drugs such as dexamethasone, and work underway to repurpose drugs like favipiravir and molnupiravir that were designed for other viruses.

"The ultimate utility of our long-acting injectable can only be determined in adequately powered and well controlled randomised clinical trials but unlike other drugs that have been explored for repurposing niclosamide target concentrations may be achievable in humans. The formulation has shown great promise in preclinical studies at a time when it is increasingly evident that drugs are urgently required to compliment the vaccines.

"A global pandemic requires a global solution, and it is critical that interventions are available to everyone and not to the privileged few. Accordingly, we are currently working to remove obstacles to availability in low- and middle-income countries to ensure equitable access if clinical success is ultimately demonstrated."

This research paper builds on previous reports released from the team in April 2020 and published in Clinical Pharmacology and Therapeutics. The CELT team have strongly advocated in further publications in the British Journal of Clinical Pharmacology, that repurposing of drugs requires new strategies that encompass reformulation and specific dose optimisation that addresses the needs of SARS-CoV-2 treatment.

New Johns Hopkins University simulations offer an intriguing look into Saturn's interior, suggesting that a thick layer of helium rain influences the planet's magnetic field.

The models, published this week in AGU Advances, also indicate that Saturn's interior may feature higher temperatures at the equatorial region, with lower temperatures at the high latitudes at the top of the helium rain layer.

It is notoriously difficult to study the interior structures of large gaseous planets, and the findings advance the effort to map Saturn's hidden regions.

"By studying how Saturn formed and how it evolved over time, we can learn a lot about the formation of other planets similar to Saturn within our own solar system, as well as beyond it," said co-author Sabine Stanley, a Johns Hopkins planetary physicist.

Saturn stands out among the planets in our solar system because its magnetic field appears to be almost perfectly symmetrical around the rotation axis. Detailed measurements of the magnetic field gleaned from the last orbits of NASA's Cassini mission provide an opportunity to better understand the planet's deep interior, where the magnetic field is generated, said lead author Chi Yan, a Johns Hopkins PhD candidate.

By feeding data gathered by the Cassini mission into powerful computer simulations similar to those used to study weather and climate, Yan and Stanley explored what ingredients are necessary to produce the dynamo--the electromagnetic conversion mechanism--that could account for Saturn's magnetic field.

"One thing we discovered was how sensitive the model was to very specific things like temperature," said Stanley, who is also a Bloomberg Distinguished Professor at Johns Hopkins in the Department of Earth & Planetary Sciences and the Space Exploration Sector of the Applied Physics Lab. "And that means we have a really interesting probe of Saturn's deep interior as far as 20,000 kilometers down. It's a kind of X-ray vision."

Strikingly, Yan and Stanley's simulations suggest that a slight degree of non-axisymmetry could actually exist near Saturn's north and south poles.

"Even though the observations we have from Saturn look perfectly symmetrical, in our computer simulations we can fully interrogate the field," said Stanley.

Direct observation at the poles would be necessary to confirm it, but the finding could have implications for understanding another problem that has vexed scientists for decades: how to measure the rate at which Saturn rotates, or, in other words, the length of a day on the planet.

The incorporation of boron into polycyclic aromatic hydrocarbon systems leads to interesting chromophoric and fluorescing materials for optoelectronics, including organic light-emitting diodes (OLEDS) and field-effect transistors, as well as polymer-based sensors. In the journal Angewandte Chemie, a research team has now introduced a new anionic organoborane compound. Synthesis of the borafluorene succeeded through the use of carbenes.

Borafluorene is a particularly interesting boron-containing building block. It is a system of three carbon rings joined at the edges: two six-membered and one central five-membered ring, whose free tip is the boron atom. While neutral, radical, and cationic (positively charged) borafluorene compounds are quite easy to produce, there have been few examples of anionic (negatively charged) borafluorene compounds to date. Better understanding of their chemistry is important for advances in redox-dependent applications and could lead to new materials with unique bonding or optical properties. However, the relatively high reactivity of borafluorene anions makes their synthesis challenging. A team led by Robert J. Gilliard, Jr. at the University of Virginia Charlottesville, USA) and David J. D. Wilson at Latrobe University (Melbourne, Australia) has now succeeded in the isolation and structural characterization of these elusive anions.

The starting point for their new synthesis is 9-bromo-9-borafluorene, which has a bromine atom attached to its boron atom. This is treated with a very strong reducing agent (potassium graphite, sodium naphthalenide, or lithium naphthalenide) in the presence of special carbenes (organic compounds with a divalent carbon atom and a free electron pair). The anionic borafluorenes formed in the reduction are stabilized by the carbenes.

As the team demonstrated, the carbene-borafluorene anions can also be used as chemical building blocks. This makes it possible to produce new compounds that are not otherwise accessible with previously known starting materials. For example, compounds with bonds between boron and gold, selenium, or germanium were generated. Reaction with a diketone led to a ring closure and bonding of the boron atom to both ketone oxygens, forming what is known as a spirocyclic boron compound.

Proteins perform a vast array of functions in the cell of every living organism with critical roles in almost every biological process. Not only do they run our metabolism, manage cellular signaling and are in charge of energy production, as antibodies they are also the frontline workers of our immune system fighting human pathogens like the coronavirus. In view of these important duties, it is not surprising that the activity of proteins is tightly controlled. There are numerous chemical switches that control the structure and, therefore, the function of proteins in response to changing environmental conditions and stress. The biochemical structures and modes of operation of these switches were thought to be well understood. So a team of researchers at the University of Göttingen were surprised to discover a completely novel, but until now overlooked, on/off switch that seems to be a ubiquitous regulatory element in proteins in all domains of life. The results were published in Nature.

The researchers investigated a protein from the human pathogen Neisseria gonorrhoeae that causes gonorrhea, a bacterial infection with over 100 million cases worldwide. This disease is typically treated with antibiotics but increasing rates of antibiotic resistance pose a serious threat. In order to identify new treatments, they studied the structure and mechanism of a protein that is a key player in carbon metabolism of the pathogen. Surprisingly, the protein can be switched on and off by oxidation and reduction (known as a "redox switch). The scientists suspected this was caused by a common and well-established "disulfide switch" formed between two cysteine amino acids. When they deciphered the X-ray structures of the protein in the "on" and "off" state at the DESY particle accelerator in Hamburg, Germany, they were hit by an even bigger surprise. The chemical nature of the switch was completely unknown: it is formed between a lysine and a cysteine amino acid with a bridging oxygen atom.

"I couldn't believe my eyes," says Professor Kai Tittmann, who led the study, when he remembers seeing the structure of the novel switch for the first time. "We thought initially that this must have formed artificially as a by-product of the experimental process as this chemical entity was unknown." However, numerous repetitions of the experiments always gave the same result and an analysis of the protein structure database further disclosed that there are many other proteins that very likely possess this switch, which apparently escaped earlier detection as the resolution of the protein structure analysis was insufficient to detect it for certain. The researchers admit that good fortune was on their side because the crystals they measured allowed the protein structure to be determined at extremely high resolution, meaning the novel switch couldn't be missed. "The extensive screening for high-quality protein crystals has really paid off, I couldn't be happier," says Marie Wensien, first author of the paper.

The researchers believe the discovery of the novel protein switch will impact the life sciences in numerous ways, for instance in the field of protein design. It will also open new avenues in medical applications and drug design. Many human proteins with established roles in severe diseases are known to be redox-controlled and the newly discovered switch is likely to play a central role in regulating their biological function as well.

Magnetic Resonance Imaging (MRI) images are usually meant to be static. But now, researchers from Mātai Medical Research Institute (Mātai), Stevens Institute of Technology, Stanford University, the University of Auckland and other institutions, report on an imaging technique that captures the brain in motion in real time, in 3D and in stunning detail, providing a potential diagnostic tool for detecting difficult-to-spot conditions such as obstructive brain disorders and aneurysms - before they become life threatening.

The new technique, called 3D amplified MRI, or 3D aMRI, reveals pulsating brain movement which could help researchers to non-invasively visualise brain disorders and inform better treatment strategies for tiny deformations or disorders that obstruct the brain or block the flow of brain fluids.

Samantha Holdsworth, director of research at Mātai, senior lecturer at the University of Auckland and principle investigator at the Centre for Brain Research, and Mehmet Kurt, an assistant professor of mechanical engineering at Stevens Institute of Technology, have now published two papers on aMRI in collaboration with Stanford University, the University of San Diego California, Queens University, and the Icahn School of Medicine at Mount Sinai.

The first paper, published online today in Magnetic Resonance in Medicine, presents the 3D aMRI method, comparing it with its 2D aMRI predecessor. The new method results in a stunning visualization of the human brain's movement that can be seen in all directions. The second paper, published online today in Brain Multiphysics, visualizes, validates and quantifies both the amplitude and direction of the brain as it moves in three dimensional space. The validation and quantification ensures that the software processing reflects an amplified version of real movement.

The approaches reported in the two papers could hold important clinical insights for a number of brain disorders. For example, the abnormal motion of two areas at the base of the brain, the pons and cerebellum, has been proposed as a diagnostic marker of Chiari I malformation, an abnormality that causes brain tissue to extend into the spinal canal.

2D amplified MRI was developed by Holdsworth, Mahdi Salmani Rahimi, Itamar Terem and other collaborators at Stanford, enabling MRI imaging to capture brain motion in a way that had previously never been seen before. 3D amplified MRI builds on this previous work developed and published in 2016. The aMRI algorithm uses a video motion processing method developed by Neal Wadhwa, Michael Rubinstein, Fredo Durand, William Freeman and colleagues at Massachusetts Institute of Technology.

"The new method magnifies microscopic rhythmic pulsations of the brain as the heart beats to allow the visualization of minute piston-like movements, that are less than the width of a human hair," explained Terem, a graduate student at Stanford and lead author of the first paper. "The new 3D version provides a larger magnification factor, which gives us better visibility of brain motion, and better accuracy."

3D aMRI of the human brain shows minute movements of the brain at an unprecedented spatial resolution of 1.2mm3, approximately the width of a human hair. The actual movements are amplified (made larger, up to 25 times) to allow clinicians and researchers to view the movements in detail. The striking detail of these animated magnified movements may be able to help identify abnormalities, such as those caused by blockages of spinal fluids, which include blood and cerebrospinal fluid.

"We showed that 3D aMRI can be used for the quantification of intrinsic brain motion in 3D, which implies that 3D aMRI holds great potential to be used as a clinical tool by radiologists and clinicians to complement decision making for the patient's treatment," said Mehmet Kurt, from the Stevens Institute of Technology and senior author of the second paper. "In my lab at Stevens, we are already seeing the benefits of using variants of 3D aMRI technique in a variety of clinical conditions including Chiari Malformation I, hydrocephalus, and aneurysms, in collaboration with clinicians at Mount Sinai."

A number of research projects are underway using the new imaging software. Holdsworth said, "We are using 3D aMRI to see if we can find new insights into the effect of mild traumatic brain injury on the brain. She added, "One study already underway, a collaboration between Mātai and the University of Auckland, uses 3D aMRI together with brain modelling methods to see whether we can develop a non-invasive way of measuring brain pressure, which may in some cases remove the need for brain surgery". This could be valuable clinically, for example, in children with idiopathic intracranial hypertension who often require invasive brain pressure monitoring.

Miriam Sadeng, an associate professor at the University of Auckland in the department of anatomy and medical imaging, who is a physician and is an author on both papers said, "This fascinating new visualization method could help us understand what drives the flow of fluid in and around the brain. It will allow us to develop new models of how the brain functions, that will guide us in how to maintain brain health and restore it in disease or disorder."

"Validating the method through computational modelling gave us further confidence about the potential impact of this work," said Javid Abderezaei, a graduate student in Kurt's lab at Stevens and lead author on the second paper. "What is exciting to see is that the dominant displacement patterns in the healthy brain qualitatively matched with the underlying physiology, which means that any changes in the physiological flow as a result of a brain disorder should be reflected in the displacements we measure."

The capability to view the differences in brain motion could help us better understand a variety of brain disorders. In the future, the technology could be expanded to use in other health disorders throughout the body.

BIRMINGHAM, Ala. - Last year, Charles O. Elson, M.D., demonstrated a potential preventive treatment for Crohn's disease, a form of inflammatory bowel disease. He used a mouse model that included immune-reactive T cells from patients with Crohn's disease in a flagellin peptide-specific immunotherapy. This study provided proof-of-principle that a flagellin-directed immunotherapy might provide similar benefits in patients.

Now University of Alabama at Birmingham researchers have moved a step closer to possible clinical testing of this treatment, say Elson and co-first authors Katie Alexander, Ph.D., and Qing Zhao, M.D., Ph.D. Their study, published in the journal
Gastroenterology, is the first to describe IgG antibodies in Crohn's disease specific for human-derived flagellins of bacteria belonging to the Lachnospiraceae family. Knowledge of the specific flagellin epitopes that drive the pathogenic adaptive immune response in Crohn's disease is necessary information for Elson's potential triple-punch Crohn's disease treatment. Goals of the treatment are removing or exhausting pathogenic T memory cells and increasing the number of immunomodulatory T regulatory cells.

Elson is a professor, Alexander an assistant professor and Zhao a postdoctoral fellow in the UAB Department of Medicine Division of Gastroenterology and Hepatology.

Crohn's disease and ulcerative colitis -- another type of inflammatory bowel disease -- are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the human specificity of these responses had so far been largely undefined. Mouse microbiota flagellins have previously been defined as immunodominant antigens in Crohn's disease.

Flagellins are building blocks of the hairlike motility flagella that extend from the bacterial cell wall. Flagellin is a potent immune activator and antigen, and it is the only known microbial protein that has three receptors for innate immunity encoded in the host genome, in addition to immunoglobulin and T cell receptors.

The UAB researchers individually probed blood sera from 87 healthy volunteers, 152 patients with Crohn's disease and 170 patients with ulcerative colitis. They used protein arrays of microbiota bacterial flagellins of both mouse and human origin, and they analyzed sera for IgG and IgA antibody responses.

They found selective patterns of antibody reactivity to microbiota flagellins among the inflammatory bowel disease patients.

The Crohn's disease patients -- but not the ulcerative colitis patients -- had augmented serum IgG antibodies to Lachnospiraceae flagellins from various species of Roseburia and one species of Eubacterium. These bacteria are normal residents in the human ileum, the third segment of the small intestine. A subset of the Crohn's disease patients had very high responses, with antibodies against more than 10 different flagellins.

For that subset of Crohn's disease patients, the multiflagellin hyper-reactivity was associated with indications of severe dysregulated immune response. Patients in the subset had: 1) elevated flagellin-specific T memory cells; 2) a reduced ratio of flagellin-reactive T regulatory to T effector cells; and 3) a high frequency of disease complications.

"Thus," Elson said, "Crohn's disease patients displayed a strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies."

Researchers have created a probe that glows when it detects an enzyme associated with issues that can lead to blood clots and strokes.

The team of researchers, from the Department of Chemistry and the National Lung and Heart Institute at Imperial College London, demonstrated that their probe quickly and accurately detects the enzyme in modified E. Coli cells.

They are now expanding this proof-of-concept study, published in the Journal of the American Chemical Society and funded by the British Heart Foundation (BHF), with the hope of creating rapid tests for cardiovascular problems and a new way to track long-term conditions.

The build-up of plaque in the arteries - known as atherosclerosis - can lead to coronary artery disease and stroke, and is one of the leading causes of death in the Western world.

As atherosclerosis progresses, intraplaque haemorrhages (IPHs) can occur when portions of the plaque break away from the artery walls. These events can lead to the formation of more vulnerable plaques and blood clots, restricting blood flow to the heart and the brain and potentially leading to chronic diseases or catastrophic events like strokes.

Detecting IPHs and their impacts would therefore provide a warning system and allow early diagnosis of vascular conditions. The research team designed a chemical probe that can detect rises in levels of an enzyme that accompanies IPHs and even plaque instabilities that precede IPHs.

Study co-lead Professor Nicholas Long, from the Department of Chemistry at Imperial, said: "Progress in the field of early cardiovascular disease has been rather limited and slow-paced but this new probe, and others that we are developing, will go a long way to addressing this by providing real-time and easily measured responses to diagnostic enzymes."

Study co-lead Dr Joe Boyle, from the National Heart and Lung Institute, added: "Ultimately, these probes could provide the basis for diagnostic tests at the GP, ambulances or in hospitals for quick identification of cardiovascular diseases. The probes could also provide real-time analysis of the underpinning biological processes involved in vascular disease, providing new insights and potentially new ways to track the progress of chronic disease."

The team's probe works by detecting an enzyme that is released in large quantities during IPHs, called heme oxygenase-1 (HO-1). Previous attempts to screen for HO-1 have been unreliable and cannot be used to detect real-time changes, but the new probe addresses both these issues.

The probe is made up of two components that can host fluorescent (glowing) molecules - one 'donor' that transfers the fluorescent molecules to the 'acceptor' component. When the probe comes into contact with HO-1, the bond between the two components is severed, leading to the build-up of the fluorescent molecules in the donor component.

This build-up causes an increase in the fluorescence intensity of the probe that can be detected using spectroscopy. In tests using modified E. coli cells containing human HO-1, the team detected a six-fold increase in the fluorescence of the probe.

Professor James Leiper, associate medical director at the BHF, said: "Current methods to detect IPH rely on hospital-based imaging techniques that are both time consuming and expensive. The current technology aims to produce a fast and sensitive diagnostic test that can be used at the time that a patient first presents with symptoms to allow early detection of IPH. Use of such a test would allow for more rapid treatment and improved outcomes for patients suffering from IPH."

The team are now extending their studies to mammal and human cells. They have recently patented their probe and have received funding from the British Heart Foundation to make a new generation of probes for other cardiovascular and neurodegenerative diseases, and to carry out more in-depth biological investigations of the underlying mechanisms.

Biodiversity is of crucial importance to the marine ecosystem. The prohibition of trawling activities in the Hong Kong marine environment for two and a half years has significantly improved biodiversity, an inter-university study led by City University of Hong Kong (CityU) has found. Research results showed that the trawl ban could restore and conserve biodiversity in tropical coastal waters.

The research team was led by Professor Kenneth Leung Mei-yee, CityU's Director of the State Key Laboratory of Marine Pollution (SKLMP) and Chair Professor in the Department of Chemistry. The findings were published in the journal Communications Biology, titled "Recovery of tropical marine benthos after a trawl ban demonstrates linkage between abiotic and biotic changes".

Trawling captures animals of all sizes

Trawling is the practice of dragging fishnets across the seabed to sweep up fishes. "Trawlers capture animals of all sizes and cause severe damages to the seabed. Also, trawling raises plumes of sediment from the seabed and induces their suspension in the water. Therefore, organisms living on the seabed which feed on those sediments would be lack of food, and biodiversity loss has resulted," said Professor Leung.

Since 31 December 2012, the Hong Kong SAR Government has implemented a territory-wide trawling ban in Hong Kong waters with the hope of rehabilitating the marine benthic habitat. To investigate whether such intervention can facilitate ecosystem recovery, the research team led by Professor Leung collected sediment samples with five replicates from each of 28 locations in Hong Kong waters in June 2012 (half-year before the trawl ban) and two and a half years after the trawl ban and then examined for physicochemical properties of the sediment and diversity of benthic animals (usually live at the bottom of a body of water).

Substantial increases in richness of species and abundance of benthic marine organisms

The results of this study suggested the trawling ban has reduced pressure on the marine environment from fishing and has led to substantial increases in the richness of species and the abundance of benthic marine organisms.

Compared to the survey conducted in 2012, the average amount of suspended solids was reduced by 1.36 mg/L, a reduction of about 25%, in the water column while the average amount of total organic matter was increased by 1.6 mg/L (an increase of about 29%) in surface sediment after the ban, indicating decreased disturbance on marine benthic habitats.

In addition, there were significant increases in abundance and species richness of benthic organisms after the ban. The average number of benthic species found in sediment samples increased from 27.5 to 48.3 species (an increase of 76%). In each 0.5 m2 of the sampling area, the average amount of all benthic organisms found in sediment samples increased from 253 to 848 individuals (an increase of 235%). Such increases were more prominent in polychaete worms and bivalves.

Rapid recovery in benthic marine ecosystem

"These small benthic organisms actually play a very crucial role as they are the main source of food for fishes, crabs and mantis shrimps. Because of the trawl ban, their abundance increases lead to an increase in the abundance of the bigger creatures, hence rehabilitating the fisheries resources," said Professor Qiu Jianwen from Hong Kong Baptist University (HKBU), one of the corresponding authors of this paper and a member of SKLMP.

Parallel studies conducted by the team revealed that fish and crustacean stocks in eastern and western waters in Hong Kong had recovered after comparing their diversity before (2004 and 2012) and after the trawl ban (2013 to 2016). It is revealed that in each km2 sampling area, the average number of predatory crabs increased 5 times from 86 in 2004 to 516 individuals in 2015 to 2016 in eastern waters, while in western waters, the number of predatory crabs greatly increased 12 times from 157 to 2101 individuals. Similarly, the number and weight of all fishes or all predatory fishes also increased in eastern and western waters after the trawl ban.

"After the trawl ban, the mantis shrimps samples we collected were longer and heavier than the previous ones. Moreover, the biomass of fish and crustaceans in the eastern and western waters has increased, which is encouraging. Our study suggested a rapid recovery of Hong Kong's benthic ecosystem and the fisheries resources in 3.5 years after the trawl ban," stressed Professor Leung.

The team conducted over 100 times of on-site survey. A postdoctoral fellow, 4 PhD students and a master student helped in the species identification and numeration of a large number of samples, as well as data processing and analysis.

Multi-pronged approach to promote ecosystem restoration

"Our results are highly encouraging and supportive of the Hong Kong SAR Government's trawl ban policy. Gratifyingly, Hong Kong has provided such a good example of successful management intervention for promoting sustainable fisheries development and marine biodiversity conservation. We hope that other countries, especially those in the tropics, will refer to our study and join forces to prohibit destructive trawling activities," said Professor Leung.

He described this study as "rare but essential" because their investigation only represented the second trawl ban study carried out in the tropics among the 71 relevant studies in the world. He hoped that the results of this research could draw the attention of governments around the world to the impact of trawl fishing on marine ecosystems. After the paper was published, Professor Leung was invited by Sciaena, a marine science and cooperation organisation in Portugal, to share the findings. He was also interviewed by the staff of the Food and Agriculture Organization of the United Nations.

"Apart from trawl ban, a multi-pronged approach can promote ecosystem restoration. For example, stop illegal trawling by increasing enforcement, improve water quality, impose a fish moratorium, control fishing gears, restrict the size of harvested fishes, establish fishery protection areas, and also minimise marine construction works," elaborated Professor Leung.

Machine learning algorithms can leverage vast amounts of consumer data, allowing automation of business decisions such as pricing, product offerings, and promotions. Airbnb, an online marketplace for vacation rentals and other lodging, created an algorithm-based smart-pricing tool that is free to all Airbnb hosts and allows hosts to set their properties' daily price automatically. A new study investigated the impact of Airbnb's algorithm on racial disparities among Airbnb hosts. Adopting the tool narrowed the revenue gap between White and Black hosts considerably, but because far fewer Black hosts used the algorithm, the revenue gap between White and Black hosts actually increased after the tool's introduction.

The study, by researchers at Carnegie Mellon University (CMU), is forthcoming Marketing Science.

"The disparity in revenues earned by White and Black hosts has been the subject of a lot of negative publicity for Airbnb in the last few years," explains Param Vir Singh, Professor of Business Technologies and Marketing at CMU's Tepper School of Business, who led the study. "Our results show that a smart-pricing algorithm can be effective in mitigating racial disparities, but that effectiveness is limited by the extent to which the tool is adopted."

The pricing algorithm was introduced in November 2015, and the study ran from July 2015 to August 2017. Researchers randomly selected 9,396 Airbnb properties in 324 zip codes, primarily in seven large U.S. cities; 2,118 hosts adopted the algorithm during the study. Researchers looked at each property's average daily revenue by month. Hosts' race/ethnicity (White, Black, or other) was determined from profile photos of host pages.

Prior to the introduction of the algorithm, White hosts earned $12.16 more in daily revenues than Black hosts after controlling for other observed host, property, and neighborhood characteristics. While both Black and White hosts charged similar prices for their properties, demand for rentals hosted by Black hosts was 20% less than that for White hosts. This suggests the presence of racial biases among Airbnb guests against Black hosts, the researchers concluded.

Adopting the algorithm benefited Black hosts in the study more than White hosts, according to the study. This is because it led to a much larger increase in demand for rentals hosted by Black hosts than for rentals hosted by White hosts, largely because demand for rentals hosted by Black hosts was more responsive to price changes than that for rentals hosted by White hosts.

But Black hosts were 41% less likely than White hosts to adopt the algorithm. Thus, while adopting the tool narrowed the revenue gap between White and Black hosts in the study, when researchers applied their findings at the population level, the revenue gap increased.

Even though Black and White hosts faced different demand curves, the price suggested by the algorithm was the same across Black and White hosts. This is because the algorithm pools the data of Black and White hosts to determine the same optimal price for both groups, in effect, ignoring racial differences between hosts. As a result, although the optimal price suggested by the algorithm should lie between the optimal price for Black hosts and the optimal price for White hosts, since fewer Black hosts adopted the algorithm, the suggested optimal price is likely to be closer to the optimal price for White hosts and farther than that for Black hosts.

"Our study has implications for policymakers and managers," says Kannan Srinivasan, Professor of Management, Marketing, and Business Technologies at CMU's Tepper School, who coauthored the study. "For policymakers, our study shows that when racial biases exist in the marketplace, an algorithm that ignores those biases may not succeed in reducing racial disparities.

"Given the much lower rate of adoption of the algorithm by Black hosts than White hosts, managers may want to devise strategies to encourage Black hosts to adopt the algorithm," Shunyuan Zhang, Assistant Professor of Marketing at Harvard Business School and co-author added. "Otherwise, an algorithm that could reduce disparities may end up increasing them."

An Austrian-American research team (University of Vienna, Department Evolutionary Anthropology and Harvard Medical School, Department of Genetics), in collaboration of Hungarian experts from Eötvös Loránd University, has developed a new method that allows the almost non-destructive extraction of genetic material from archaeological human remains. The method allows anthropologists, archaeologists and archaeogeneticists to avoid the risk of serious damage to artefacts of significant scientific and heritage value, which can then be fully examined in future research.

Bioarcheological research on human and animal remains from archaeological excavations has become increasingly important in recent decades. Both nationally and internationally, in addition to classical archaeological and anthropological research, a significant number of molecular biological way of examination are included. One of the most important fields is archaeogenetics. The study of ancient human and animal genetic material can significantly help both the analysis of human evolution and the answering of historical questions about the populations of later archaeological periods.

The first archaic DNA (aDNA) research started in the 1980s, but the real methodological breakthroughs came after the turn of the millennium. This was the period when next-generation sequencing methods reached bioarcheological research. Thanks to the large-scale research that began at that time, we now know more than 60% of the DNA of Neanderthals preserved in the nuclei of cells. A new human species was described on the basis of the genetic material extracted from teeth and finger bones found in Siberia, and it was recognised that, contrary to previous ideas, Neanderthal man and modern Homo sapiens interbred with each other, that left significant genetic traces in modern human groups north of the Sahara.

However, these samples for archaeogenetic analyses may involve a high degree of destruction and may therefore be of concern from a heritage conservation perspective, preventing or making it difficult to obtain and carry out the sampling.

An international team of researchers (Ron Pinhasi laboratory at the University of Vienna and David Reich' laboratory at Harvard) has recognised this problem and has recently developed several new sampling methods to minimise the bone damage associated with sampling. Firstly, the methodological basis for drilling into the inner ear from the cranial base was developed and later it was shown that the use of auditory ossicles can significantly reduce the damage in the fining during sampling.

The latest research, published in the journal Genome Research, was carried out by the above-mentioned international team and the researchers of the Department of Anthropology (Tamás Hajdu, Krisztián Kiss, Tamás Szeniczey) and the Institute of Archaeology (Alexandra Anders, Pál Raczky) at Eötvös Loránd University.

„The new method significantly reduces the extent of damage of the findings. It consists of dissolving the DNA content of the root fragment of the tooth, rich in cellular cementum, by immersing it in a special solution. The quality of the sample thus obtained is not as good as that of DNA extracted from the inner ear, but it is of the same quality as that of the genetic material obtained by traditional methods (drilling and pulverisation of the tooth). The main advantage of the method is that the tooth undergoes only to minimal damage, leaving its structure intact not only morphologically but also histologically, while its unchanged chemical composition allows subsequent isotopic tests (strontium or C14) to be carried out. The only noticeable change is the fading or whitening of the root colour" - told Tamas Hajdu, head of the Hungarian research group, Assistant Professor at the Department of Anthropology at Eötvös Loránd University.

The significance of the new sampling method, therefore, lies in its minimal destructive effect. If the sampled teeth are left intact, they can be subjected to further morphological, radiological, histological, oral pathological, stable isotope and radiocarbon studies. This may be particularly important in cases where only a few teeth remain have been preserved from a given period and place, which may be tens of thousands of years old, and destructive sampling of these would completely preclude subsequent analysis. In addition to human evolutionary research, the new methodology could also help projects on population history and disease evolution at the Department of Anthropology and the Institute of Archaeology, at Eötvös Loránd University by preserving the integrity of the findings. The new sampling method, developed in international cooperation, offers a new perspective for the preservation of artefacts for national and international museum institutions, while at the same time allowing for the almost non-destructive conduct of the latest archaeogenetic analyses.

ENDING:

The international team of researchers has developed a new sampling method and tested its effectiveness on human material from several archaeological sites in Hungary and abroad. The Hungarian archaeological material can be found in the collections of the Hungarian Natural History Museum, the Herman Ottó Museum, the Déri Museum and the Damjanich János Museum. The new method was initiated by Ron Pinhasi' research group at the Department of Evolutionary Anthropology, the University of Vienna and the methodological background was worked out, and the bone and tooth samples were analysed, and the Austrian team and David Reich' Laboratory at the Department of Genetics, Harvard Medical School. The anthropological background of the findings was provided by the Department of Anthropology at Eötvös Loránd University and Department of Anthropology at the Hungarian Natural History Museum and the Institute of Archaeology, ELKH-BTK (Tamás Hajdu, Tamás Szeniczey, Krisztián Kiss, Ildikó Pap, Kitti Köhler). The basic archaeological background data of the research (archaeological age, cultural classification, archaeological context of the finds) were provided by the joint work of the research staff of several Hungarian institutions (ELTE BTK Archaeological Institute: Alexandra Anders, Pál Raczky; Déri Museum: János Dani, Barbara Kolozsi, Emese Gyöngyvér Nagy; Herman Otto Museum: B. Hellebrandt Magdolna, Horváth Antónia; ELKH BTK Archaeology Institute: Király Ágnes; Damjanich János Museum: Kovács Péter; Ásatárs Kft.)

With increased media attention and political campaigns focusing on the gender pay gap, the fact that women -- on average -- are paid less than men, has become an important public discussion. While much of the focus has been on the corporate sector, a new study that looked at executive compensation at nonprofit organizations found that women earn 8.9% less than men with the gap becoming greater when there is room for salary negotiations.

The study co-authored by Curtis Hall, PhD, an associate professor in Drexel University's LeBow College of Business; Andrew R. Finley, assistant professor at the Robert Day School of Economics and Finance at Claremont McKenna College; and LeBow College of Business doctoral student Amanda R. Marino, analyzed data from IRS form 990 filings--where salaries of executuves in nonprofits are publicly disclosed--for four years across various industries.

The researchers first looked at whether or not a gap in pay does exist among executives in the nonprofit sector and then, the extent to which negotiation opportunities -- either real or perceived -- contribute to this difference.

"For various reasons we may not expect to observe a gender pay gap among the nonprofit sector even though recent research has found gaps in pay among for-profit executives," said Hall. "First, there is more female participation in the nonprofit workforce compared to the for-profit sector. Second, one may expect stakeholders, like donors or boards of directors to curtail gender pay gaps, but we didn't find this to be enough of a factor to prevent gender pay gaps."

To better understand the role of negotiation in contributing to the pay gap, the researchers examined settings with an expected variation in opportunities and willingness to negotiate. They looked at external employment options for the nonprofit executives, the organization's constraints in paying executives, the gender composition of its leadership and the pay variability within its executive ranks. Each of these factors uniquely influences the negotiation environment, according to the authors.

They found that executives' external employment options and competition lead to greater gender pay gaps with male executives more likely to capitalize on a broader external labor market or other opportunities to negotiate additional compensation.

However, in organizations with higher female board representation, and/or the presence of a female CEO, the pay gap is reduced. This may be because female leadership increases the willingness of female employees to negotiate, according to the authors.

"This study documents the contexts that influence negotiation on the gender pay gap, which is part of a larger societal issue," said Hall. "Employers should be cognizant of how the environment for negotiating compensation within their organizations can lead to gender-based pay disparities. Perhaps more importantly, business leaders and educators should think about ways to empower female workers to get more out of salary negotiations, which would hopefully help to close gender pay gaps in the future."