Culture

The LIGO Scientific Collaboration and the Virgo Collaboration recently announced the discovery of GW190521, the most massive gravitational wave binary observed to date, and Rochester Institute of Technology scientists played an important role in identifying and analyzing the event. They detected the signal with the National Science Foundation's Laser Interferometer Gravitational-wave Observatory (LIGO). The two inspiralling black holes had masses of about 85 and 66 solar masses, and resulted in the formation of a black hole remnant of 142 solar masses, providing the first clear detection of an "intermediate-mass" black hole.

"We're seeing something more massive than we've seen before, past the point where we thought that we could form black holes," said Associate Professor Richard O'Shaughnessy, a member of CCRG and the LIGO Scientific Collaboration. "It's therefore suggesting that our previous understanding was incomplete or maybe there's more out there than we previously envisioned."

Not only were the black holes in this event larger than those detected previously, the signal indicates that they could have been spinning about their own axes, at angles that were out of alignment with the axis of their orbit. The black holes' misaligned spins likely caused their orbits to wobble, or "precess," as the they spiraled toward each other.

Jacob Lange '20 Ph.D. (astrophysical sciences and technology) is a recent alum who contributed heavily to the analysis, using RIT-developed parameter estimation code and direct comparisons to numerical relativity simulations to estimate and corroborate the unique features of the event, including the masses and spin of the black holes. He said he is excited about the discovery because it challenges previous assumptions about black hole formation and raises important new questions about the fundamentals of how gravity works.

"We thought it would be almost impossible for us to measure precession at this high mass but somehow we were able to do it and it's not really clear why that was the case," said Lange. "It's not what we expected to be able to detect and hopefully we can learn a lot more from it."

The discovery and its implications are outlined in two papers published in Physical Review Letters and The Astrophysical Journal Letters and 10 researchers from RIT's Center for Computational Relativity and Gravitation are listed among the authors. RIT's contributions also included providing computer simulations of Albert Einstein's equations by co-authors Professor Carlos Lousto and Research Associate James Healy used to compare the signal with and developing a waveform catalog.

While previous black holes detected by the European Virgo and the U.S. National Science Foundation LIGO are believed to have formed by collapsing stars, theory suggests that black holes with masses between 65 and 120 times the mass of the sun cannot be formed by this method. This perhaps means that intermediate black holes may form by another method, such as Pacman-like behavior where black holes grow by merging with smaller black holes.

"As LIGO and Virgo keep showing us, the universe is full of surprises," said Professor John Whelan, principal investigator of RIT's group in the LIGO Scientific Collaboration, an active group of 17 faculty, students and postdoctoral researchers. For more on RIT's work with the LIGO Scientific Collaboration, visit the CCRG website.

BAR HARBOR, MAINE -- Scientists have long known that chronic stress experienced early in life, or even chronic prenatal exposure to maternal stress hormones in the womb, can shorten lifespan and contribute to age-related chronic diseases like arthritis, asthma, cancer, cardiovascular disease, diabetes and even mental illness later in life -- long after the source of stress has been removed.

But the mechanisms behind these effects are not well understood.

Now, a team of scientists at the MDI Biological Laboratory in Bar Harbor, Maine, is shedding new light on the gene regulatory pathways activated by cortisol, a hormone secreted by the adrenal glands in response to stress. The team, which uses the common aquarium fish, the zebrafish, as a model, is led by associate professor James A. Coffman, Ph.D.

Chronic stress is known to lead to persistently elevated cortisol, an important regulator of inflammation. Persistently elevated cortisol can, in turn, make cells more resistant to the hormone, undermining its ability to effectively control inflammation, although the mechanisms for this are not well understood, Coffman said. Such dysregulation sets the stage for the development of chronic inflammation and inflammatory disease.

The Coffman team has found that chronic cortisol exposure affects gene activity mainly via the glucocorticoid receptor (GR), a transcriptional regulatory protein (a protein responsible for orchestrating gene activity) that is activated by cortisol. They have also found that upregulation of proinflammatory gene activity in cortisol-treated zebrafish depends as well on a GR target gene called klf9, another transcriptional regulator.

"In healthy individuals the immune system behaves like a well-regulated militia that responds rapidly to the body's commands to mobilize or stand down, mounting an inflammatory response that persists only as long as needed to clear an infection or stimulate wound healing," Coffman explained. "We believe klf9 is a key gene for understanding the optimal regulation of inflammation and how it is compromised by early-life stress."

In humans, chronic stress can be caused by psychosocial factors such as trauma, economic adversity or the struggle to cope with abusive circumstances, Coffman said. He noted that such stress, which is already endemic in many communities, is currently being exacerbated by the COVID-19 pandemic.

The identification of klf9 as a key regulator of the physiological response to cortisol builds on earlier research in which Coffman showed that chronic exposure to cortisol early in life has persistent effects on the stress response system that compromise the regulation of key immune system genes controlling inflammation.

The paper based on the new research, entitled "Klf9 Is a Key Feedforward Regulator of the Transcriptomic Response to Glucocorticoid Receptor Activity," was recently published in Scientific Reports, an online journal from the publishers of Nature.

The research was conducted in zebrafish because they are relatively easy and economical to work with and because they share their stress response system with humans, along with the associated regulatory genes and gene circuitry. In his earlier studies, Coffman found that zebrafish larvae treated with cortisol for the first five days of life had increased proinflammatory gene activity and gave rise to adults with a dysregulated immune response.

Coffman is especially intrigued by the role that klf9 may play in "inflammaging," a chronic, low-grade inflammation that is believed to accelerate aging and exacerbate many age-related diseases. In the future, he would like to explore the role of klf9 in age-related neurodegenerative diseases such as Alzheimer's.

Another potential area for investigation is klf9's role in regeneration. Because regenerative ability has been found to depend on the immune system, a better understanding of the immune system's response to stress could help explain the connection between chronic stress and impaired healing ability.

"The new study on klf9 highlights the potential synergies that can occur between scientists working in aging and regeneration, the lab's two areas of research," said Hermann Haller, M.D., president. "It also demonstrates the importance of basic research: science will only be able to able to develop new therapies for treating aging and age-related disease by understanding the underlying mechanisms."

"Klf9 has become a research focus of my lab because it's interesting in a lot of different respects -- not just in terms of the stress response," Coffman said. "It's an important gene with its fingers in a lot of different regulatory pathways and it is understudied. In the future, we will seek to identify how klf9 optimizes immune cell responsiveness to cortisol and how those functions are compromised in aging."

The study was enabled by the CRISPR gene editing technology, which allows scientists to create genetically modified mutants with the attributes they are seeking to study. In this case, zebrafish were developed in which the genes encoding the GR and Klf9 were deactivated, which allowed scientists to compare the stress response in normal fish with those of their genetically altered counterparts.

Adjuvants are a key ingredient of many modern vaccines, working to unleash an immune response that helps protect the body from disease. Many scientists believe that adjuvants are they key to developing new kinds of vaccines for hard-to-vaccinate viruses, like HIV.

But adjuvants can cause inflammation at the injection site, as well as side effects from an over-stimulated immune system, which prohibits many promising new adjuvant candidates from being integrated into vaccines.

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have discovered a new way to limit inflammation from adjuvants: by adding a molecule that disrupts certain pathways in cells. Not only does it reduce inflammatory vulnerability, the molecule also appears to have an additional benefit of increasing the protective response against viruses like the flu, dengue, and even HIV. It could also eventually be used in the development of a vaccine for SARS-CoV-2, the virus that causes COVID-19.

Results were published Sept. 9 in the journal Science Advances.

"This could lead to a new way of designing vaccines," said Assoc. Prof. Aaron Esser-Kahn, who led the research. "It goes against the traditional view that increased inflammation is necessary, and in doing so it provides even more protection. It's more beneficial than we could have hoped."

Disrupting pathways that cause inflammation

For years, researchers have been exploring toll-like receptor (TLR) agonists as adjuvants, since they activate the inflammatory cytokines that can result in successful vaccines. One such agonist, called CpG DNA, has shown promise as an adjuvant, and has even been shown to provide protection against HIV. But TLR agonists like CpG DNA can induce excessive inflammatory response in the body, making them difficult to implement in vaccine development.

"In the vaccine field, you hear over and over again that you just have to accept the response that comes with an individual molecule," Esser-Kahn said. "But we wanted to find a way to limit the ability of a cell's response to produce the cytokines that are associated with inflammation. We wanted to decouple the initial, unneeded inflammation from the immune system response that is actually productive."

Esser-Kahn and his group found that a peptide called SN50 could disrupt the pathways in cells that lead to this initial inflammation. Specifically, it disrupted a protein called NF-kB, which is known for its role in producing inflammatory cytokines.

By adding it to a wide range of TLR agonists, they found that it decreased inflammation and, more surprisingly, increased antibodies against diseases.

"It's very simple, and doesn't require a lot of additional material," Esser-Kahn said. "It's a tweak in the way the cell processes information."

Molecule effective against flu, HIV

To test its effectiveness, the researchers tested it in mouse models of several different diseases. For dengue, they found that the molecule helped produce more antibodies that neutralized the virus. For HIV, they found that it helped produce antibodies that targeted a difficult-to-reach part of the virus - overcoming one of the roadblocks that has made an HIV vaccine so difficult to create.

When the researchers added the molecule to an already-available flu vaccine, they found it increased the vaccine's level of protection against the disease.

"We thought that the molecule would decrease inflammation, but we were surprised to see that it could provide more protection at the same time," Esser-Kahn said.

Next the researchers hope to find a small molecule, instead of a peptide, that could perform that same task, and are looking into how such a molecule could also help immunotherapy interventions for cancer and other diseases. In the future, this research could benefit new vaccines for SARS-CoV-2, especially if the virus mutates to become seasonal.

"The approach has a lot of implications for how we might design vaccines over the next five or ten years," Esser-Kahn said.

What do vapers, smokers, and non-smokers with chronic conditions such as high blood pressure or diabetes have in common? They all are at higher risk for COVID-19.

The scientific explanation behind this is complex and not yet certain -- but it may boil down to an enzyme known as ACE2, that lives on the surface of many cells in the lungs and serves as the entry point for the coronavirus.

Evidence shows that people with chronic inflammatory illnesses, vulnerable older adults, and those who smoke or vape, all have an abundance of ACE2 receptor proteins to serve as a gateway to the deadly virus.

A research team at the University of Rochester Medical Center, led by Irfan Rahman, Ph.D., published a series of studies during the pandemic that focus on the vital role of ACE2 -- which is already at the center of many other scientific investigations -- to shape a clearer picture of the critical cellular mechanisms that regulate the deadly virus and its link to vaping.

While Rochester investigators are working in lock step with scientists around the world, Rahman's special interest is on the growing problem of young people who test positive and may be spreading coronavirus at alarming rates. Even some older children and teens who have higher levels of the ACE2 receptor seem to be more vulnerable to the virus.

"Our next step is to investigate whether ACE2 is normally low in young people, hence their relatively low infection and mortality rates from COVID-19, but to find out if ACE2 is increased by smoking or vaping rendering them more susceptible to the virus," said Rahman, Dean's Professor of Environmental Medicine , Medicine (Pulmonary), and Public Health Sciences. "This would be in contrast to older people with lung diseases such as COPD and pulmonary fibrosis, who we already know are at higher risk for severe viral illnesses and death."

A post-doctoral scientist in Rahman's lab, Gangandeep Kaur, Ph.D., had prior experience investigating tuberculosis and thus led the new effort to study ties between vaping and coronavirus. The team has published several key peer-reviewed articles relevant to the issue:

Smoking, combined with aging, alters more than 20 genes involved in lung cell function and results in a spike in ACE2 receptors and three other proteins associated with the coronavirus, according to a Rahman study in Frontiers in Pharmacology. This strengthens the observations of other researchers, that smokers and people with chronic lung diseases such as COPD are more prone to coronavirus infection.

Because vaping and smoking tend to be long-term habits, URMC researchers investigated the chronic effects of nicotine exposure on lung tissue in mice, keeping an eye open for links to known COVID-19 proteins. They discovered other receptors with a direct relationship to ACE2, which also have a significant role in regulating the inflammatory response in the lungs and cause a higher expression of ACE2. This was reported in the Respiratory Research journal and may provide a gene target for the treatment of lung inflammation caused by smoking or vaping.

In a June review article written by Rahman and Guiseppe Lungarella, M.D., of the University of Siena, Italy, where COVID-19 swept through the country earlier than in the U.S., they draw additional connections between ACE2 receptors, smokers, and coronavirus. For example, their analysis shows: In Wuhan, China, patients who smoked did worse; fatality rates were higher for men, who have more ACE2 receptors, than in women; and that ACE2 is linked to known nicotine receptors. Kaur, the postdoctoral fellow, is also a co-author.

The review suggests that health care providers should ask patients about their smoking and vaping history, to better identify people who could be at higher risk for coronavirus complications, according to the Journal of Inflammation article. Currently, the Rahman lab is examining blood and saliva samples of young people who have been infected with COVID-19 to evaluate ACE2 levels and see if the ACE2 protein can be a biomarker for a rapid coronavirus test.

In other recent studies, Rahman and URMC scientists disclosed the 40 chemicals used in flavoring e-liquids and vaping pods, detailing their harmful effects on lung tissue; and demonstrated that vaping is associated with wheezing, which is often a precursor to emphysema, reflux disease, heart disease, lung cancer and sleep apnea.

BIRMINGHAM, Ala. - Type 1 diabetes, or T1D, is an autoimmune disease in which the body's immune cells -- led by inflammatory macrophages -- attack and destroy the beta cells of the pancreas that produce insulin.

Researchers have long tried to unravel the signaling that provokes this attack. One of the less-studied forms of signaling is inflammatory lipids.

In a study published in JCI Insight, Sasanka Ramanadham, Ph.D., and colleagues at the University of Alabama at Birmingham, at other universities in the United States and in Greece have identified a proinflammatory lipid profile that precedes development of T1D in a mouse model and in children under the age 15 who are at high risk for T1D.

This finding may identify candidate lipid therapeutic targets to prevent T1D.

Phospholipase A2, or PLA2, enzymes can release a free fatty acid from glycerophospholipids. When the free fatty acid is arachidonic acid, it can be metabolized by several other enzyme classes to produce oxidized bioactive lipids, including some potent inflammatory eicosanoids.

One of the phospholipase A2 enzymes is a calcium-independent phospholipase A2, designated iPLA2-beta. Its activation promotes poor outcomes in experimental and clinical diabetes.

Ramanadham and others have shown that iPLA2-beta participates in programmed cell death, or apoptosis, of beta cells, modulating inflammatory polarization of macrophages, and promoting T-cell immune responses.

"In light of these observations," said Ramanadham, a professor in the UAB Department of Cell, Developmental and Integrative Biology and senior scientist in the UAB Comprehensive Diabetes Center, "we used lipidomics to gain insight into the lipidome associated with T1D development in spontaneous-T1D-prone non-obese diabetic mice, or NOD mice, and in humans at high risk for developing T1D."

Female NOD mice show a progression of T1D, and an inhibitor can show the importance of iPLA2-beta on T1D development. About 80 to 90 percent of NOD mice become diabetic by 25 to 30 weeks of age; but if the iPLA2-beta inhibitor FKGK18 is given to the mice, starting at 10 days, only 10 to 15 percent of the NOD mice develop diabetes. But if the inhibitor was started later, at four or eight weeks, the researchers saw that about 60 or 80 percent, respectively, of the mice developed diabetes.

Because of this apparent temporal impact of iPLA2-beta-derived lipids on T1D development, the researchers looked at the macrophage (a recognized initiator of immune responses leading to T1D) lipid profiles from NOD mice and from C57 mice, a control strain that does not develop diabetes. Isolated peritoneal macrophages from NOD mice showed a profound proinflammatory lipid profile during the prediabetic phase, as well as higher levels of iPLA2-beta mRNA.

The researchers then showed that early inhibition of iPLA2-beta by FKGK18, or genetic reduction of iPLA2-beta in a NOD mouse line with only one copy of the iPLA2-beta gene, resulted in: 1) reduced production of select proinflammatory lipids by macrophages, 2) promotion of an anti-inflammatory macrophage phenotype and 3) reduction in the incidence of T1D.

In addition, the researchers showed that the pro-inflammatory lipid changes in NOD macrophages were reflected in the blood plasma of NOD mice during the prediabetic phase and at T1D onset. Additionally, and importantly, they found similar pro-inflammatory lipid signatures in the blood plasma of male and female children between 9 and 15 years of age, who were at high risk for developing T1D, as measured by autoantibodies.

"These findings," Ramanadham said, "suggest that iPLA2-beta-derived lipids contribute to T1D onset, and they identify select lipids that could be targeted for therapeutics and -- in conjunction with autoantibodies -- serve as early biomarkers of pre-T1D."

The diabetes drug metformin--derived from a lilac plant that's been used medicinally for more than a thousand years--has been prescribed to hundreds of millions of people worldwide as the frontline treatment for type 2 diabetes. Yet scientists don't fully understand how the drug is so effective at controlling blood glucose.

Now, researchers at the Salk Institute have shown the importance of specific enzymes in the body for metformin's function. In addition, the new work showed that the same proteins, regulated by metformin, controlled aspects of inflammation in mice, something the drug has not typically been prescribed for. Apart from clarifying how metformin works, the research, which appeared in the journal Genes & Development on September 10, 2020, has relevance for many other inflammatory diseases.

"These findings let us dig into precisely what metformin is doing at a molecular level," says Reuben Shaw, a professor in Salk's Molecular and Cell Biology Laboratory and the senior author of the new paper. "This more granular understanding of the drug is important because there is increasing interest in targeting these pathways for not only diabetes but immune diseases and cancer."

Researchers have known for 20 years that metformin activates a metabolic master switch, a protein called AMPK, which conserves a cell's energy under low nutrient conditions, and which is activated naturally in the body following exercise. Twelve years ago, Shaw discovered that in healthy cells, AMPK starts a cascade effect, regulating two proteins called Raptor and TSC2, which results in a block of the central pro-growth protein complex called mTORC1 (mammalian target of rapamycin complex 1). These findings helped explain the ability of metformin to inhibit the growth of tumor cells, an area of research that began to generate excitement after Shaw and others connected AMPK to a bona fide cancer gene in the early 2000s.

But in the intervening years, many additional proteins and pathways that metformin regulates have been discovered, drawing into question which of the targets of metformin are most important for different beneficial consequences of metformin treatment. Indeed, metformin is currently entering clinical trials in the United States as a general anti-aging treatment because it is effects are so well established from millions of patients and its side effects are minimal. But whether AMPK or its targets Raptor or TSC2 are important for different effects of metformin remains poorly understood.

In the new work, in mice, Shaw and his colleagues genetically disconnected the master protein, AMPK, from the other proteins, so they could not receive signals from AMPK, but were able to otherwise function normally and receive input from other proteins.

When these mice were put on a high-fat diet triggering diabetes and then treated with metformin, the drug no longer had the same effects on liver cells as it did in normally diabetic animals, suggesting that communication between AMPK and mTORC1 is crucial for metformin to work.

By looking at genes regulated in the liver, the researchers found that when AMPK couldn't communicate with Raptor or TSC2, metformin's effect on hundreds of genes was blocked. Some of these genes were related to lipid (fat) metabolism, helping explain some of metformin's beneficial effects. But surprisingly, many others were linked to inflammation. Metformin, the genetic data showed, normally turned on anti-inflammatory pathways and these effects required AMPK, TSC2 and Raptor.

"We didn't go looking for a role in inflammation, so for it to come up so strongly was surprising," says Salk postdoctoral fellow and first author Jeanine Van Nostrand.

People suffering from obesity and diabetes often exhibit chronic inflammation, which further leads to additional weight gain and other maladies including heart disease and stroke. Therefore, identifying an important role for metformin and the interrelationship between AMPK and mTORC1 in control of both blood glucose and inflammation reveals how metformin can treat metabolic diseases by multiple means.

Metformin and exercise elicit similar beneficial outcomes, and research has previously shown that AMPK helps mediate some of the positive effects of exercise on the body, so among other questions, Shaw and Van Nostrand are interested in exploring whether Raptor and TSC2 are involved in the many beneficial effects of exercise, as well.

"If turning on AMPK and shutting off mTORC1 are responsible for some of the systemic benefits of exercise, that means we might be able to better mimic this with new therapeutics designed to mimic some of those effects," says Shaw, who holds the William R. Brody Chair.

In the meantime, the new data suggest that researchers should study the potential use of metformin in inflammatory diseases, particular those involving liver inflammation. The findings also point toward AMPK, Raptor and TSC2 more broadly as potential targets in inflammatory conditions, suggesting the need for a deeper investigation of metformin, as well as newer AMPK agonists and mTOR inhibitors, the researchers say.

Purifying specific protein molecules from complex mixtures will become easier with a simpler way to detect a molecular "tag" commonly used as a handle to grab the proteins.

Proteins, comprising many linked amino acid molecules, form the key "workforce" of molecular biology, performing a multitude of chemical tasks, including catalyzing the chemistry of life, switching genes on and off, and receiving and responding to signals between cells.

Researchers need to produce and purify selected proteins to investigate their activities for drug research, biotechnology and basic investigations of cell biology.

Proteins of interest are commonly made by inserting the genes that code for them into cells that will produce them, but that leaves the problem of identifying and purifying the desired protein from a potentially complex mixture. A common strategy is to modify the gene encoding the protein to make the protein carry a string of molecules of the amino acid called histidine, creating a "polyhistidine tag."

"The tag acts like a handle attached to a bag," explains the first author of the study, Vlad-Stefan Raducanu. "It's much easier to fish out a protein by catching the tag."

The various proteins in an impure sample can be separated using an electric field to pull them through a gel at different rates--a process called gel electrophoresis. The gel is then transferred to a membrane and the region carrying the polyhistidine-tagged proteins is visualized using antibodies, also a form of protein, to selectively bind to the tag. However, this type of detection can be laborious.

Now, Raducanu and his colleagues have developed a simpler detection procedure that avoids the membrane transfer step and the use of antibodies.

They constructed a chemical complex that binds to polyhistidine tags and can be stimulated by ultraviolet (UV) radiation to fluoresce with visible light. The regions of the gel carrying tagged proteins can be readily detected by the light given off by the UV-excited "fluorophore" complexes bound to the tags.

"It was challenging to devise a suitable UV-excitable fluorophore," Raducanu explains. The team had to couple the fluorescent component of their complex to another part containing a metal ion that can bind to the polyhistidine tag.

"We now plan to collaborate with chemists at KAUST to develop even brighter dyes," Raducanu says, expressing hope that the usefulness of UV-excitable fluorophores could be adopted more widely to help researchers detect the proteins they need.

A recent study has shown that readers' eye gaze behaviors are strong indicators of words that are unexpected, new, or difficult to understand. The study by Rain Bosworth, an assistant professor and researcher in the Center for Sensory, Perceptual, and Cognitive Ecology (SPaCE Center) at Rochester Institute of Technology's National Technical Institute for the Deaf, explores the unknown qualities of gaze behavior for "sign watching" and how these are affected by a user's language expertise and intelligibility of the sign input.

According to Bosworth's study, published in the Journal of Deaf Studies and Deaf Education, with NTID graduate Adam Stone, gaze behaviors can provide an index of cognitive effort and knowledge in signers. This study provides the first evidence that novice and fluent signers have different eye gaze behaviors.

Bosworth and her team recorded gaze behaviors in 52 deaf and hearing adults while they watched signed narratives. Highly fluent signers primarily kept a steady gaze on the face and used peripheral vision to perceive the signers' moving hands. The researchers then showed the participants videos of signed stories played backwards. Bosworth said that people who learned American Sign Language earlier in life are better equipped to understand difficult video-reversed narratives. Fluent signers tended to focus strongly on the face when sign watching, even for low intelligibility conditions.

"These low intelligibility conditions simulate what happens in real-world settings when trying to watch live signers on phones with small displays or with weak internet signals," explained Bosworth.

Novice signers, who scored lower on measures of story comprehension, showed a very different gaze pattern.

"Gaze behavior is more scattered for people who recently learned sign language, and this scatter increased for low-intelligibility conditions, probably because observers are looking directly at the moving hands," Bosworth said. "This fits with what we know about research that shows that signers have very good peripheral vision, especially from the lower visual field. Expert signers look at the face and utilize their peripheral vision for catching the fine details of moving handshapes."

But, there is some good news for non-signers. According to Bosworth, it doesn't take long for signers to develop "expert-like" gaze patterns during sign comprehension. Hearing signers who have been signing for at least five years often show steady gaze behavior on the face just like fluent deaf signers.

DURHAM, N.C. -- You know the type: Loud. Swaggering. Pushy. The alpha male clearly runs the show. Female alphas are often less conspicuous than their puffed up male counterparts, but holding the top spot still has its perks.

Wearing the crown means privileged access, like never having to wait your turn. And now, a study of female baboons points to another upside to being No. 1: less stress.

In a Duke University-led study, researchers describe how, after 18 years of collecting fecal samples from 237 female baboons in Amboseli National Park in Kenya, they found that alpha females have significantly lower levels of glucocorticoids, hormones produced in response to stress.

Baboon females are a very orderly group, with one reigning alpha who gets her way over everyone else, a second-in-command who dominates all but the alpha, and so on down to the bottom-ranked female, who gets pushed around by most everyone.

Dominance gives baboons a lot of advantages in life. Higher-ranking females get preferential treatment in grooming bouts and first dibs at feeding time. As a result, their babies grow faster and are more likely to survive to adulthood.

Considering all these perks, the researchers say it came as no surprise that higher status means lower glucocorticoids. They found that the larger a female's share of subordinates, the lower her glucocorticoid levels.

But what puzzled the team was why the top-ranking females stood out so much from the rest. Their stress hormone levels were 8% lower than everyone else in their group.

The findings were surprising because baboons aren't like some other species with clear-cut "queens," said first author Emily Levy, a biology Ph.D. student in Susan Alberts' lab at Duke.

Top-ranking baboon females don't claim exclusive rights to reproduction, as in some other species.

"You don't usually look at an alpha female baboon and see a bully," Levy said.

The researchers aren't sure what drives the disparity between leaders and non-leaders in baboon females, but suggest two possible explanations.

It could be that alpha females experience less stress because they hold their position longer than other females, Levy said.

A baboon matriarch rules in a society in which power is handed down from mother to daughter. All but the top-ranking female eventually cede their spot to their daughters as they get older. But once ensconced in power, alphas have been known to rule for eight years or more.

Take Pindua, an alpha female who ruled unchallenged until she died in 1989. Only then did her daughter assume the throne, recalls Alberts, who has spent 30 years studying wild baboons as part of the Amboseli Baboon Research Project.

"She was definitely a Grand Dame -- very calm and non-reactive, but unambiguous about her power," Alberts said.

There's another reason why the alpha female may be different from the others on measures of stress hormones, Alberts said. It's that there's no female above her to push her around.

The alpha female only has herself to answer to, Alberts said. She goes where she pleases. "Nobody's going to mess with her."

Previous research by Alberts and colleagues at Princeton University found the opposite pattern for alpha male baboons. Top-ranked males have the highest levels of stress hormones, presumably because instead of inheriting their status, as females do, males have to fight to stay on top.

"In male baboons you can just watch the alpha for a day and say, wow, that individual is kicking everybody's butt," Levy said. "For females it's a little more nuanced."

East Hanover, NJ. September 9, 2020. A team of U.S. researchers published the results of a multi-center, single-arm trial of the ReWalk ReStore™ for gait training in individuals undergoing post-stroke rehabilitation. They found the device safe and reliable during treadmill and overground walking under the supervision of physical therapists. The article, "The ReWalk ReStore soft robotic exosuit: a multisite clinical trial of the safety, reliability, and feasibility of exosuit-augmented post-stroke gait rehabilitation," was published open access in the Journal of NeuroEngineering and Rehabilitation on June 18, 2020 (doi: 10.1186/s12984-020-00702-5).

The authors are the principal investigators of each of the five testing sites: Louis N. Awad, PT, DPT, PhD, of Spaulding Rehabilitation Hospital, Boston, MA, Alberto Esquenazi, MD, of MossRehab Stroke and Neurological Disease Center, Elkins Park, PA, Gerard E. Francisco, MD, of TIRR Memorial Hermann, Houston, TX, Karen J, Nolan, PhD, of Kessler Foundation, West Orange, NJ, and lead investigator Arun Jayaramam, PT, PhD, of the Shirley Ryan AbilityLab, Chicago, IL.

Open Access link: https://jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-020-00702-5

The ReStore™ exosuit (ReWalk Robotics, Ltd) is the first soft robotic exosuit cleared by the FDA for use in stroke survivors with mobility deficits. The device is indicated for individuals with hemiplegia undergoing stroke rehabilitation under the care of licensed physical therapists. Hemiplegia causes weakness of the ankle, limiting the ability to clear the ground during stepping and hindering forward movement. This leads to compensatory walking patterns that increase effort and decrease stability.

ReStore is designed to augment ankle plantarflexion and dorsiflexion, allowing a more normal gait pattern. Motors mounted on a waist belt transmit power through cables to attachment points on an insole and the patient's calf. Sensors clipped to the patient's shoes transmit data to a handheld smartphone controller used by a trained therapist to adjust levels of assistance and monitor and record key metrics of gait training.

The trial enrolled 44 participants with post stroke hemiparesis who were able to walk unassisted for 5 feet. The protocol consisted of 5 days of 20-minute sessions of treadmill and overground training under the supervision of licensed physical therapists. To assess the therapeutic potential for ReStore in rehabilitation, the researchers also explored the effects of the device on maximum walking speed, measuring participants' walking speed in and out of the device using the 10-m walk test, before and after the five training visits. For safety purposes, some participants were allowed to use an AFO or cane during walking sessions.

The trial determined the safety, reliability, and feasibility of the device in this stroke population. "We found that the ReStore provided targeted assistance for plantarflexion and dorsiflexion of the paretic ankle, improving the gait pattern," explained Dr. Nolan, senior research scientist in the Center for Mobility and Rehabilitation Engineering Research at Kessler Foundation. "This is an important first step toward expanding options for rehabilitative care for the millions of individuals with mobility impairments caused by ischemic and hemorrhagic stroke."

The trial's exploratory data indicated positive effects of the training on the walking speed of participants during exosuit-assisted walking and unassisted walking (walking without the device). More than one third of participants achieved a significant increase in unassisted walking speed, indicating that further research is warranted.

Dr. Nolan emphasized that the trial was not designed to measure the device's efficacy: "Controlled trials are needed to determine the efficacy of ReStore for improving mobility outcomes of stroke rehabilitation."

ARLINGTON, Va.--How can the Department of the Navy (DoN) best harness the power and potential of artificial intelligence (AI) to address everything from operating efficiency at sea to corporate excellence?

These questions will be discussed by leaders from the Office of Naval Research (ONR) during two panel sessions at the Department of Defense (DoD) Artificial Intelligence Symposium and Exposition, held Sept. 9-10, 2020.

The two-day virtual event is sponsored by the DoD's Joint Artificial Intelligence Center (JAIC). It will bring together government, business and academic experts to focus on delivering AI-enabled solutions to benefit warfighters; strengthen national security; and improve the effectiveness, affordability and speed of military operations.

On Thursday, Sept. 10, at 2:30 p.m., Chief of Naval Research Rear Adm. Lorin C. Selby will participate in a session titled "Rigging for AI," which will discuss how to best position the sea services for accelerated AI development and adoption.

Later that day, at 3:15 p.m., ONR will preside over another session showcasing the AVENGER Naval AI Grand Challenge--an initiative intended to maximize military-civilian AI partnerships, and promote greater innovation within AI development processes.

"In naming the challenge AVENGER, we took inspiration from the Battle of Midway," said Navy Chief AI Officer Brett Vaughan, who is part of the team overseeing AVENGER. "Midway was a pivotal momentum shift in World War II and saw the debut of the Avenger torpedo bomber, an aircraft that revolutionized naval operations.

"Much like the role the Avenger aircraft played in Midway, our expectation is that the AVENGER Naval AI Challenge will catalyze a tide-turning effort in the campaign to accelerate AI development and adoption," continued Vaughan, who also is ONR's AI portfolio manager.

The AVENGER Naval AI Grand Challenge is a collaboration involving the Navy Chief AI Officer; ONR; the Deputy Chief of Naval Operations for Warfighting Development (OPNAV N7); the NavalX Agility Cell; the Navy's Digital Transformation Office; JAIC; and various naval laboratories and warfare centers.

The challenge connects Navy and Marine Corps AI developers with experts in industry, academia and the government to address problems ranging from knowledge management and data maintenance to base security and small-unit maneuvers. The goal is to develop fleet-tested solutions within a year and scaled capabilities within 18 months.

Vaughan said a primary objective of AVENGER is to evaluate the effectiveness of the current naval innovation pipeline to remove barriers to AI adoption and create best practices for getting technology solutions to the fleet faster.

People who were children when their parents were divorced showed lower levels of oxytocin -- the so-called "love hormone" -- when they were adults than those whose parents remained married, according to a study led by Baylor University. That lower level may play a role in having trouble forming attachments when they are grown.

Oxytocin -- secreted in the brain and released during bonding experiences such as delivery of a baby or sexual interaction or nursing, even being hugged by a romantic partner -- has been shown in previous research to be important for social behavior and emotional attachments in early life. The oxytocin system also has been linked to parenting, attachment and anxiety.

The new study, published in the Journal of Comparative Psychology, delves into an area that has not been well researched -- a link between oxytocin, early experience and adult outcomes.

"Since the rates of divorce in our society began to increase, there has been concern about the effects of divorce on the children," said lead author Maria Boccia, Ph.D., professor of child and family studies at Baylor University in the Robbins College of Health and Human Sciences. "Most research has focused on short-term effects, like academic performance, or longer-term outcomes like the impact on relationships. How divorce causes these effects, however, is unknown.

"Oxytocin is a neurohormone that is important in regulating these behaviors and is also sensitive to the impact of stressful life events in early life," she said. "This is a first step towards understanding what mechanisms might be involved."

Previous studies of children whose parents were divorced have found that the experience was associated with mood disorders and substance abuse -- behaviors found to be related to oxytocin, Boccia said. Additionally, such childhood experiences as divorce or death of a parent are associated with depression and anxiety in adolescents and adults, as well as with poorer parenting in adulthood, less parental sensitivity and warmth, overreaction and increased use of punishment.

Researchers in the Baylor study examined the effect of the experience of parental divorce in childhood on later adult oxytocin levels. They also asked participants to complete a set of questionnaires on attachment style and other measures.

"What we found was that oxytocin was substantially lower in people who experienced parental divorce compared to those who did not and correlated with responses on several measures of attachment," Boccia said. "These results suggest that oxytocin levels are adversely affected by parental divorce and may be related to other effects that have been documented in people who experience parental divorce."

Animal studies also suggest that one mechanism contributing to the negative effects of early parental separation may be suppression of oxytocin activity.

For the latest study, researchers recruited 128 individuals ages 18 to 62 at two institutions of higher learning in the Southeast United States. Of those, 27.3% indicated their parents were divorced. The average age for participants when their parents divorced was 9 years.

Upon arriving at the study site, participants were asked to empty their bladders, then given a 16-ounce bottle of water to drink before filling out questionnaires about their parents and peers during childhood, as well as their current social functioning. The questions addressed their parents' style, including affection, protection, indifference, over-control and abuse; and their own levels of confidence, discomfort with closeness, need for approval and their styles of relationships and caregiving.

After participants completed the questionnaires, urine samples were collected, and researchers analyzed oxytocin concentrations. The levels were substantially lower in individuals whose childhood experience included their parents' divorce.

Further analysis showed that those individuals rated their parents as less caring and more indifferent. They also rated their fathers as more abusive. Those who experienced parental divorce during childhood were less confident, more uncomfortable with closeness and less secure in relationships. They rated their own caregiving style as less sensitive and close than did the participants whose parents had not divorced.

"One of the first questions I am asked when presenting this research to other scientists is 'does how old the child is when the divorce occurs matter?' That is the most pressing question that we need to explore," Boccia said.

ITHACA, N.Y.- Using publicly available tourist photos of world landmarks such as the Trevi Fountain in Rome or Top of the Rock in New York City, Cornell University researchers have developed a method to create maneuverable 3D images that show changes in appearance over time.

The method, which employs deep learning to ingest and synthesize tens of thousands of mostly untagged and undated photos, solves a problem that has eluded experts in computer vision for six decades.

"It's a new way of modeling scenes that not only allows you to move your head and see, say, the fountain from different viewpoints, but also gives you controls for changing the time," said Noah Snavely, associate professor of computer science at Cornell Tech and senior author of "Crowdsampling the Plenoptic Function," presented at the European Conference on Computer Vision, held virtually Aug. 23-28.

"If you really went to the Trevi Fountain on your vacation, the way it would look would depend on what time you went - at night, it would be lit up by floodlights from the bottom. In the afternoon, it would be sunlit, unless you went on a cloudy day," Snavely said. "We learned the whole range of appearances, based on time of day and weather, from these unorganized photo collections, such that you can explore the whole range and simultaneously move around the scene."

Representing a place in a photorealistic way is challenging for traditional computer vision, partly because of the sheer number of textures to be reproduced. "The real world is so diverse in its appearance and has different kinds of materials - shiny things, water, thin structures," Snavely said.

Another problem is the inconsistency of the available data. Describing how something looks from every possible viewpoint in space and time - known as the plenoptic function - would be a manageable task with hundreds of webcams affixed around a scene, recording data day and night. But since this isn't practical, the researchers had to develop a way to compensate.

"There may not be a photo taken at 4 p.m. from this exact viewpoint in the data set. So we have to learn from a photo taken at 9 p.m. at one location, and a photo taken at 4:03 from another location," Snavely said. "And we don't know the granularity of when these photos were taken. But using deep learning allows us to infer what the scene would have looked like at any given time and place."

The researchers introduced a new scene representation called Deep Multiplane Images to interpolate appearance in four dimensions - 3D, plus changes over time. Their method is inspired in part on a classic animation technique developed by the Walt Disney Company in the 1930s, which uses layers of transparencies to create a 3D effect without redrawing every aspect of a scene.

"We use the same idea invented for creating 3D effects in 2D animation to create 3D effects in real-world scenes, to create this deep multilayer image by fitting it to all these disparate measurements from the tourists' photos," Snavely said. "It's interesting that it kind of stems from this very old, classic technique used in animation."

In the study, they showed that this model could be trained to create a scene using around 50,000 publicly available images found on sites such as Flickr and Instagram. The method has implications for computer vision research, as well as virtual tourism - particularly useful at a time when few can travel in person.

"You can get the sense of really being there," Snavely said. "It works surprisingly well for a range of scenes."

ST. LOUIS - A team of researchers led by Kenton Johnston, Ph.D., an associate professor of health management and policy at Saint Louis University's College for Public Health and Social Justice, conducted a study investigating the association between health system affiliations of clinicians and their performance scores and payments under Medicare value-based reimbursement.

Their findings, "Association of Clinician Health System Affiliation with Outpatient Performance Ratings in the Medicare Merit-based Incentive Payment System," were published online Sept. 8 in the Journal of the American Medical Association.

The researchers found that clinicians who were affiliated with health systems had better performance scores and received fewer payment penalties and more payment bonuses under the Medicare Merit-based Incentive Payment System (MIPS) than clinicians not affiliated with health systems.

"Physicians need to take the MIPS seriously. More and more of outpatient physicians' payments from Medicare will be tied to their performance under the MIPS," Johnston said. "Payment penalties and bonuses will hit 9 percent of physicians' total Medicare reimbursement by 2022. There are things physician practices can do to maximize their success on the MIPS. But this requires the management, administration and technological infrastructure to report performance measures to the Centers for Medicare and Medicaid Services."

The study used 2019 MIPS data to examine 636,552 clinicians' performance and found that clinicians affiliated with health systems achieved mean performance scores of 79 versus 60 for unaffiliated clinicians, on a scale of 0 to 100. Physicians affiliated with health systems were 99 percent less likely to receive payment penalties and 29 percent more likely to receive exceptional performance bonus payments than physicians not affiliated with health systems.

Clinicians who affiliate with health systems appear to do substantially better under Medicare value-based payment. However, clinicians could self-select the performance measures they were evaluated on, so it is unclear whether findings represent real differences in patient quality of care or other factors. That is an area for future research.

Because the MIPS is a zero-sum game, Johnston said, the financial consequences are that system-affiliated clinicians are recipients of greater Medicare payment resources at the expense of clinicians not affiliated with health systems.

This is likely to amplify the existing trend toward clinician consolidation within health systems as clinicians seek sophisticated analytics, informatics, and administrative help to maximize performance and reimbursement under value-based payment programs.

MIPS, which is authorized under the Medicare Access and CHIP Reauthorization Act, is a mandatory pay-for-performance program for clinicians participating in Medicare in the outpatient setting. Clinician performance under MIPS looks at quality of care, meaningful use of electronic health records, improvement activities for patient care processes and cost.

Many complex systems have underlying networks: they have nodes which represent units of the system and their edges indicate connections between the units. In some contexts, the connections are symmetric, but in many they are directed, for example, indicating flows from one unit to another or which units affect which other units.

A prime example of this is a food web, in which the nodes represent species and there is a directed edge from each species to those which eat it. In a directed network, the ecological concept of 'trophic level' allows one to assign a height to each node in such a way that on average the height goes up by one along each edge.

The trophic levels can help to associate function to nodes, for example, plant, herbivore, carnivore in a food web. The concept was reinvented in economics, where it is called 'upstreamness', though it can be traced back to Leontief and the 'output multiplier'. It is also an ingredient in the construction of SinkRank, a measure of contribution to systemic risk.

Alongside 'trophic level', there is also 'trophic incoherence'; this is the standard deviation of the distribution of height differences along edges and it gives a measure of the extent to which the directed edges fail to line up. The trophic incoherence is an indicator of network structure that has been related to stability, percolation, cycles, normality and various other system properties.

Trophic level and incoherence are limited in various ways, however: they require the network to have basal nodes (ones with no incoming edges), the basal nodes are given too much emphasis, and if there is more than one they do not give a stable way to determine levels and incoherence for a piece of a network, and they do not give a natural notion of maximal incoherence.

In the paper, 'How directed is a directed network?', published today, the 9th September in the journal Royal Society Open Science, researchers from the University of Warwick and the University of Birmingham reveal a new method for analysing hierarchies in complex networks and illustrate it by applications to economics, language and gene expression.

The researchers introduce improved notions of trophic level and trophic coherence, which do not require basal or top nodes, are as easy to compute as the old notions, and are connected in the same way with network properties such as normality, cycles and spectral radius. They expect this to be a valuable tool in domains from ecology and biochemistry to economics, social science and humanities.

Professor Robert MacKay, from the Mathematics Institute at the University of Warwick comments:

"Our method makes hierarchical structure apparent in directed networks and quantifies the extent to which the edges do not line up. We expect it to be useful in disparate contexts, such as determining the extent of influence in a social network or organisational management, assessing the situation of the UK in the face of Brexit trade talks, illuminating how biochemical reaction networks function, and understanding how the brain works."