Culture

Philadelphia, June 24, 2021 - After beginning treatment with remdesivir for COVID-19, a patient experienced significant bradycardia, or low heart rate. Her physicians used a dopamine infusion to stabilize her through the five-day course of remdesivir treatment, and her cardiac condition resolved itself at the end of the treatment. The case is discussed in Heart Rhythm Case Reports, an official journal of the Heart Rhythm Society, published by Elsevier.

"Remdesivir has become the standard of care for COVID-19 pneumonia and there is a paucity of data on its cardiac effects," explained lead author Jomel Patrick Jacinto, DO, HCA Healthcare/USF Morsani College of Medicine GME Programs at Regional Medical Center Bayonet Point, Hudson, FL, USA. "While it is known to be well tolerated and effective, it's critical to note its potential adverse effects on the cardiovascular system. To our knowledge, this is the first reported case of remdesivir-induced hemodynamically unstable sinus bradycardia."

The patient arrived at the hospital in respiratory distress with abnormally rapid breathing, and she tested positive for COVID-19. She was admitted to the intensive care unit and was started on standard COVID-19 treatment protocol, including antiviral therapy with remdesivir. Twenty hours after administration of the first dose, her vitals revealed very low blood pressure and a heart rate as low as 38 beats per minute. An electrocardiogram found marked sinus bradycardia. She lacked any prior cardiac history and had normal telemetry monitor and ECG findings prior to receiving remdesivir. She was started on a dopamine drip and maintained normal sinus rhythm with a heart rate of 60-65 beats per minute. Eighteen hours after her last dose of remdesivir, the dopamine was titrated off, and the patient was stable, with normal ECG findings.

Dr. Jacinto observed that remdesivir has an important role in the fight against severe COVID-19 because it has been shown to improve mortality rates and shorten the total time to recovery. In this case, completion of the five-day course of remdesivir was imperative to the patient's treatment despite the adverse effects as concurrent medical treatment with pressors such as dopamine was adequate support.

"Most hospitals have the ability to support the patient through the five-day treatment course to completion, using medications such as dopamine to nullify severe bradycardia," Dr. Jacinto said. "Having a heightened awareness of its cardiac safety profile is essential to make effective clinical decisions in treatment of patients with remdesivir." He added that remdesivir should be used cautiously in patients with known cardiovascular disease.

Motions of a remarkable cosmic structure have been measured for the first time, using NASA's Chandra X-ray Observatory. The blast wave and debris from an exploded star are seen moving away from the explosion site and colliding with a wall of surrounding gas.

Astronomers estimate that light from the supernova explosion reached Earth about 1,700 years ago, or when the Mayan empire was flourishing and the Jin dynasty ruled China. However, by cosmic standards the supernova remnant formed by the explosion, called MSH 15-52, is one of the youngest in the Milky Way galaxy. The explosion also created an ultra-dense, magnetized star called a pulsar, which then blew a bubble of energetic particles, an X-ray-emitting nebula.

Since the explosion the supernova remnant - made of debris from the shattered star, plus the explosion's blast wave - and the X-ray nebula have been changing as they expand outward into space. Notably, the supernova remnant and X-ray nebula now resemble the shape of fingers and a palm.

Previously, astronomers had released a full Chandra view of the "hand," as shown in the main graphic. A new study is now reporting how quickly the supernova remnant associated with the hand is moving, as it strikes a cloud of gas called RCW 89. The inner edge of this cloud forms a gas wall located about 35 light-years from the center of the explosion.

To track the motion the team used Chandra data from 2004, 2008, and then a combined image from observations taken in late 2017 and early 2018. These three epochs are shown in the inset of the main graphic.

The rectangle (fixed in space) highlights the motion of the explosion's blast wave, which is located near one of the fingertips. This feature is moving at almost 9 million miles per hour. The fixed squares enclose clumps of magnesium and neon that likely formed in the star before it exploded and shot into space once the star blew up. Some of this explosion debris is moving at even faster speeds of more than 11 million miles per hour. A color version of the 2018 image shows the fingers in blue and green and the clumps of magnesium and neon in red and yellow.

While these are startling high speeds, they actually represent a slowing down of the remnant. Researchers estimate that to reach the farthest edge of RCW 89, material would have to travel on average at almost 30 million miles per hour. This estimate is based on the age of the supernova remnant and the distance between the center of the explosion and RCW 89. This difference in speed implies that the material has passed through a low-density cavity of gas and then been significantly decelerated by running into RCW 89.

The exploded star likely lost part or all of its outer layer of hydrogen gas in a wind, forming such a cavity, before exploding, as did the star that exploded to form the well-known supernova remnant Cassiopeia A (Cas A), which is much younger at an age of about 350 years. About 30% of massive stars that collapse to form supernovas are of this type. The clumps of debris seen in the 1,700-year-old supernova remnant could be older versions of those seen in Cas A at optical wavelengths in terms of their initial speeds and densities. This means that these two objects may have the same underlying source for their explosions, which is likely related to how stars with stripped hydrogen layers explode. However, astronomers do not understand the details of this yet and will continue to study this possibility.

A paper describing these results appeared in the June 1, 2020, issue of The Astrophysical Journal Letters, and a preprint is available online. The authors of the study are Kazimierz Borkowski, Stephen Reynolds, and William Miltich, all of North Carolina State University in Raleigh.

In a study in Nature Plants, Yiping Qi, associate professor of Plant Science at the University of Maryland (UMD), introduces a new and improved CRISPR 3.0 system in plants, focusing on gene activation instead of traditional gene editing. This third generation CRISPR system focuses on multiplexed gene activation, meaning that it can boost the function of multiple genes simultaneously. According to the researchers, this system boasts four to six times the activation capacity of current state-of-the-art CRISPR technology, demonstrating high accuracy and efficiency in up to seven genes at once. While CRISPR is more often known for its gene editing capabilities that can knock out genes that are undesirable, activating genes to gain functionality is essential to creating better plants and crops for the future.

"While my lab has produced systems for simultaneous gene editing [multiplexed editing] before, editing is mostly about generating loss of function to improve the crop," explains Qi. "But if you think about it, that strategy is finite, because there aren't endless genes that you can turn off and actually still gain something valuable. Logically, it is a very limited way to engineer and breed better traits, whereas the plant may have already evolved to have different pathways, defense mechanisms, and traits that just need a boost. Through activation, you can really uplift pathways or enhance existing capacity, even achieve a novel function. Instead of shutting things down, you can take advantage of the functionality already there in the genome and enhance what you know is useful."

In his new paper, Qi and his team validated the CRISPR 3.0 system in rice, tomatoes, and Arabidopsis (the most popular model plant species, commonly known as rockcress). The team showed that you can simultaneously activate many kinds of genes, including faster flowering to speed up the breeding process. But this is just one of the many advantages of multiplexed activation, says Qi.

"Having a much more streamlined process for multiplexed activation can provide significant breakthroughs. For example, we look forward to using this technology to screen the genome more effectively and efficiently for genes that can help in the fight against climate change and global hunger. We can design, tailor, and track gene activation with this new system on a larger scale to screen for genes of importance, and that will be very enabling for discovery and translational science in plants."

Since CRISPR is usually thought of as "molecular scissors" that can cut DNA, this activation system uses deactivated CRISPR-Cas9 that can only bind. Without the ability to cut, the system can focus on recruiting activation proteins for specific genes of interest by binding to certain segments of DNA instead. Qi also tested his SpRY variant of CRISPR-Cas9 that greatly broadens the scope of what can be targeted for activation, as well as a deactivated form of his recent CRISPR-Cas12b system to show versatility across CRISPR systems. This shows the great potential of expanding for multiplexed activation, which can change the way genome engineering works.

"People always talk about how individuals have potential if you can nurture and promote their natural talents," says Qi. "This technology is exciting to me because we are promoting the same thing in plants - how can you promote their potential to help plants do more with their natural capabilities? That is what multiplexed gene activation can do, and it gives us so many new opportunities for crop breeding and enhancement."

LA JOLLA--(June 24, 2021) When looking at a complex landscape, the eye needs to focus in on important details without losing the big picture--a charging lion in a jungle, for example. Now, a new study by Salk scientists shows how inhibitory neurons play a critical role in this process.

The study, published May 25, 2021, in the journal Cell Reports, shows that inhibitory neurons do more than just inhibit neuron activity like an off-switch; paradoxically, they actually increase the amount of information transmitted through the nervous system when it needs to be flexible. To make this possible, inhibitory neurons need to be integrated into the circuit in a specific way. These observations could help scientists better understand and treat disorders involving our ability to focus and modulate signals based on the bigger picture, which are altered in conditions such as anxiety and attention deficit disorders.

"This work points to a new role for inhibitory neurons, which are usually just thought to be suppressors and organizers of activity," says Professor Tatyana Sharpee, who led the study. "The role of inhibitory neurons extends much further. By targeting only the most sparsely responding neurons, inhibitory neurons make it possible for the whole circuit to function well. That's completely new."

The new work was motivated by unanswered questions from a previous study of the diversity of response rates among neurons in the retina. The retina is a part of the eye that converts lights to electrical signals to be sent to the brain. "Remarkably, when we looked at retina cells that were not responding very much, their rates of information transfer actually increased in the presence of modulation," says first author Wei-Mien Hsu, a postdoctoral fellow in the Sharpee lab. "The trick for making this unexpected phenomenon possible is to apply the modulation signal via inhibitory neurons."

While the researchers tested the theory in neurons involved in vision, the findings could apply widely to neurons found throughout the brain and nervous system, adds Sharpee, who holds the Edwin K. Hunter Chair at Salk.

The next step in this line of research is to study how the phenomenon works in large sets of neurons.

UNIVERSITY PARK, Pa. -- It can be difficult to get young kids to eat enough vegetables, but a new Penn State study found that simply adding more veggies to their plates resulted in children consuming more vegetables at the meal.

The researchers found that when they doubled the amount of corn and broccoli served at a meal -- from 60 to 120 grams -- the children ate 68% more of the veggies, or an additional 21 grams. Seasoning the vegetables with butter and salt, however, did not affect consumption.

The daily recommended amount of vegetables for kids is about 1.5 cups a day, according to the official Dietary Guidelines for Americans as set by the U.S. Departments of Agriculture and Health and Human Services.

"The increase we observed is equal to about one third of a serving or 12% of the daily recommended intake for young children," said Hanim Diktas, graduate student in nutritional sciences. "Using this strategy may be useful to parents, caregivers and teachers who are trying to encourage kids to eat the recommended amount of vegetables throughout the day."

Barbara Rolls, Helen A. Guthrie Chair and director of the Laboratory for the Study of Human Ingestive Behavior at Penn State, said the findings -- recently published in the journal Appetite -- support the MyPlate guidance from the U.S. Department of Agriculture, which recommends meals high in fruits and vegetables.

"It's important to serve your kids a lot of vegetables, but it's also important to serve them ones they like because they have to compete with the other foods on the plate," Rolls said. "Parents can ease into this by gradually exposing kids to new vegetables, cooking them in a way their child enjoys, and experimenting with different flavors and seasonings as you familiarize them."

According to the researchers, the majority of children in the U.S. don't eat the recommended daily amount of vegetables, which could possibly be explained by children having a low preference for them. And while serving larger portions has been found to increase the amount of food children eat -- called the "portion size effect" -- kids tend to eat smaller amounts of vegetables in response to bigger portions compared to other foods.

For this study, the researchers were curious if increasing just the amount of vegetables while keeping the portions of other foods the same would help increase veggie consumption in kids. They also wanted to experiment with whether adding light butter and salt to the vegetables would increase their palatability and also affect consumption.

For the study, the researchers recruited 67 children between the ages of three and five. Once a week for four weeks, the participants were served lunch with one of four different preparations of vegetables: a regular-sized serving of plain corn and broccoli, a regular-sized serving with added butter and salt, a doubled serving of plain corn and broccoli, and a doubled serving with added butter and salt.

During each meal, the vegetables were served alongside fish sticks, rice, applesauce and milk. Foods were weighed before and after the meal to measure consumption.

"We chose foods that were generally well-liked but also not the kids' favorite foods," Rolls said. "If you offer vegetables alongside, say, chicken nuggets you might be disappointed. Food pairings are something you need to be conscious of, because how palpable the vegetables are compared to the other foods on the plate is going to affect the response to portion size. You need to make sure your vegetables taste pretty good compared to the other foods."

After analyzing the results, the researchers found that while the larger portions of vegetables were associated with greater intake, the addition of butter and salt was not. The children also reported liking both versions -- seasoned and unseasoned -- about the same. About 76% of kids rated the vegetables as "yummy" or "just ok."

"We were surprised that the butter and salt weren't needed to improve intake, but the vegetables we served were corn and broccoli, which may have been already familiar to and well-liked by the kids," Diktas said. "So for less familiar vegetables, it's possible some extra flavoring might help to increase intake."

Diktas said that while serving larger portions may increase vegetable consumption, it also has the potential to increase waste if kids don't eat all of the food that is served.

"We're working on additional research that looks into substituting vegetables for other food instead of just adding more vegetables," Diktas said. "In the future, we may be able to give recommendations about portion size and substituting vegetables for other foods, so we can both limit waste and promote veggie intake in children."

GRAND RAPIDS, Mich. (June 24, 2021) -- The same taste-sensing molecule that helps you enjoy a meal from your favorite restaurant may one day lead to improved ways to treat diabetes and other metabolic and immune diseases.

TRPM5 is a specialized protein that is concentrated in the taste buds, where it helps relay messages to and from cells. It has long been of interest to researchers due to its roles in taste perception and blood sugar regulation.

Now, a team led by scientists at Van Andel Institute has published the first-ever high-resolution images of TRPM5, which reveal two areas that may serve as targets for new medications. The structures also may aid in the development of low-calorie alternative sweeteners that mimic sugar. The findings were published today in Nature Structural and Molecular Biology.

"TRPM5 is the cornerstone of taste signaling, which itself has a much larger role in the body than often recognized," said Wei Lü, Ph.D., an associate professor at VAI and co-corresponding author of the study. "We hope our structures of TRPM5 will serve as blueprints for designing new medications that help control blood sugar in diabetes, while also providing a template for development of low-calorie sweeteners that activate sensory circuits in the brain and the gut -- a key distinction that mimics sugar."

There are five types of taste that the body senses: sweet, sour, salty, bitter and umami. When the tongue encounters a taste, specialized cells on the tongue called taste receptors send messages about that taste to the brain. TRPM5 is a key part of the complex process that ushers these important signals on their way to the brain's sensory processing center.

But taste perception goes far beyond helping us sense the subtle flavors of a tiramisu. It helps protect the body by detecting bitter and acidic tastes, which commonly are associated with harmful substances. Taste perception also occurs beyond the tongue; for example, the process of taste perception in certain pancreatic cells regulates insulin secretion, which keeps blood sugar levels in check. Similar cells, called tuft cells, also coat the linings of the intestine, lungs and gallbladder, where they use TRPM5 and related proteins to sense the sugar-like byproducts of parasitic infections and trigger immune responses to deal with the threat.

"Targeting TRPM5 and taste-signaling throughout the body has two major potential benefits: it may help us improve treatment for a number of metabolic and immune disorders while also providing a path toward improved sweeteners," said Juan Du, Ph.D., an associate professor at VAI and co-corresponding author of the study. "While the body needs sugar to survive, too much of it can be harmful. We're hopeful a more thorough understanding of TRPM5 will lead to better alternatives."

TRPM5 belongs to the TRP superfamily, a group of proteins that mediate responses to sensory stimuli, such as pain, pressure, vision, temperature and taste. Broadly known as ion channels, proteins like TRP nestle within cells' membranes, acting as gatekeepers for chemical signals passing into and out of the cell. The eight proteins that comprise the TRPM subfamily are part of this broader group.

To date, Lü and Du laboratories have solved the structures of three of the eight known TRPM proteins as well as an ion channel called CALHM2, which belongs to the calcium homeostasis modulator family. Another member of this molecular family is CALHM1, also an important component of taste signaling.

Rude behavior at work has come to be expected, like donuts in the breakroom. Two decades of research on employee relationships shows that 98 percent of employees experience rude behavior at work, but now a new study suggests a large majority of workplace relationships are not characterized by rudeness. Isolated incidents of rude behavior at work, although somewhat common, do not point to widespread incivility between employees and their colleagues, according to a new UCF study.

"Because prior research suggests workplace mistreatment is harmful and widespread, it is often called an epidemic, but our findings show that rude behavior is less like the flu and more like cholera," says Shannon Taylor, an associate professor of management and co-author of the report. "It is still harmful, but far less common, and outbreaks are often traced to a single source - much like a contaminated water pump."

While the study was conducted prior to the COVID-19 pandemic, Taylor says his team's findings are just as applicable to remote work environments. Collaborating remotely presents a variety of challenges that can lead to miscommunication and misinterpretation.

"As employees return to work on-site, our study suggests developing and maintaining good relationships with co-workers is important now more than ever," Taylor says.

The study, co-authored by UCF doctoral student Lauren Locklear, was published this month in the Journal of Applied Psychology. The project takes a closer look at the influence of workplace relationships on disrespectful behavior in the office.

The study examined rude behavior among restaurant, manufacturing, and office workers. Researchers found that while most employees experience rudeness at work, these experiences came from a small number of co-workers. Although 70% of employees experienced rudeness at work, only 16 percent of workplace relationships were characterized by rude behavior.

An employee's individual personality, position and other traits are major factors in determining the level of incivility present in a given workplace. Across all study groups, researchers found that unique relationships between colleagues have just as strong an influence in determining whether workers will be rude to one another.

"Even if one employee is a jerk to everyone and their co-worker is the office punching bag, there is still something about their unique relationship that explains how well they get along together," Taylor says. "Most people do experience rude behavior, but most of their relationships are not characterized by rudeness."

Behavioral expectations and workplace culture also play a key role in influencing employee mistreatment. But an employee's perceptions about how their colleagues should treat each other have a stronger impact on rude behavior than an employee's perceptions about how their colleagues actually treat each other.

"Employees' beliefs about what is 'right and wrong' at work have a big impact on what happens on the job," says Locklear. "Employers should ensure there are strong norms for respect and civility in the workplace. Having a zero-tolerance policy for these rude behaviors is key to stopping mistreatment in its tracks."

Being clear and encouraging positive interactions will be key, the study's authors say.

"Our prior work shows gratitude and appreciation are important aspects to fostering positive employee relationships and decreasing negative workplace behavior," Locklear says. "Expressing these positive behaviors will be essential in determining how smoothly we return to in-person work environments."

The brain is not a passive recipient of injury or disease. Research has shown that when neurons die and disrupt the natural flow of information they maintain with other neurons, the brain compensates by redirecting communications through other neuronal networks. This adjustment or rewiring continues until the damage goes beyond compensation.

This process of adjustment, a result of the brain's plasticity, or its ability to change or reorganize neural networks, occurs in neurodegenerative conditions such as Alzheimer's, Parkinson's and Huntington's disease (HD). As the conditions progress, many genes change the way they are normally expressed, turning some genes up and others down. The challenge for researchers like Dr. Juan Botas who studies HD, has been to determine which of the gene expression changes are involved in causing the disease and which ones help mitigate the damage, as this may be critical for designing effective therapeutic interventions.

In his lab at Baylor College of Medicine, Botas and his colleagues look to understand what causes the loss of communication or synapses between neurons in HD. Up until now, research has focused on neurons because the normal huntingtin gene, whose mutation causes the condition, contributes to maintaining healthy neuronal communication. In the current work, the researchers looked into synapses loss in HD from a different perspective.

Focusing on glia to understand Huntington's disease

The mutated huntingtin gene is not only present in neurons, but in all the cells in the body, opening the possibility that other cell types also could be involved in the condition.

"In this study we focused on glia cells, which are a type of brain cell that is just as important as neurons to neuronal communication," said Botas, professor of molecular and human genetics and of molecular and cellular biology at Baylor and a member of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital.

We thought that glia might be playing a role in either contributing or compensating for the damage observed in Huntington's disease."

Initially thought to be little more than housekeeping cells, glia turned out to have more direct roles in promoting normal neuronal and synaptic function.

In a previous work, Botas and his colleagues studied a fruit fly model of HD that expresses the human mutant huntingtin (mHTT) gene in neurons, to understand which of the many gene expression changes that occur in HD are causing disease and which ones are compensatory.

"One class of compensatory changes affected genes involved in synaptic function. Could glia be involved?" Botas said. "To answer this question, we created fruit flies that express mHTT only in glia, only in neurons or in both cell types."

Comparing changes in gene expression

The researchers began their investigation by comparing the changes in gene expression present in the brains of healthy humans with those in human HD subjects and in HD mouse and fruit fly models. They identified many genes whose expression changed in the same direction across all three species but were particularly intrigued when they discovered that having HD reduces the expression of glial cell genes that contribute to maintaining neuronal connections.

"To investigate whether the reduction of expression of these genes in glia either helped with disease progression or with mitigation, we manipulated each gene either in neurons, glial cells or both cell types in the HD fruit fly model. Then we determined the effect of the gene expression change on the function of the flies' nervous system," Botas said.

They evaluated the flies' nervous system health with a high-throughput automated system that assessed locomotor behavior quantitatively. The system filmed the flies as they naturally climbed up a tube. Healthy flies readily climb, but when their ability to move is compromised, the flies have a hard time climbing. The researchers looked at how the flies move because one of the characteristics of HD is progressive disruption of normal body movements.

Turning down the genes worked

The results revealed that in HD, turning down glial genes involved in synaptic assembly and maintenance is protective.

Fruit flies with the mutant huntingtin gene in their glial cells in which the researchers had deliberately turned down synaptic genes climbed up the tube better than flies in which the synaptic genes were not dialed down.

"Our study reveals that glia affected by HD respond by tuning down synapse genes, which has a protective effect," Botas said. "Some gene expression changes in HD promote disease progression, but other changes in gene expression are protective. Our findings suggest that antagonizing all disease-associated alterations, for example using drugs to modify gene expression profiles, may oppose the brain's efforts to protect itself from this devastating disease. We propose that researchers studying neurological disorders could deepen their analyses by including glia in their investigations."

A new research paper published in the American Journal of Clinical Nutrition last week showed that a low Omega-3 Index is just as powerful in predicting early death as smoking. This landmark finding is rooted in data pulled and analyzed from the Framingham study, one of the longest running studies in the world.

The Framingham Heart Study provided unique insights into cardiovascular disease (CVD) risk factors and led to the development of the Framingham Risk Score based on eight baseline standard risk factors--age, sex, smoking, hypertension treatment, diabetes status, systolic blood pressure, total cholesterol (TC), and HDL cholesterol.

CVD is still the leading cause of death globally, and risk can be reduced by changing behavioral factors such as unhealthy diet, physical inactivity, and use of tobacco and alcohol. Therefore, researchers in this study say biomarkers integrating lifestyle choices might help identify individuals at risk and be useful to assess treatment approaches, prevent morbidity, and delay death.

Among the diet-based biomarkers are fatty acids (FAs), whether measured in plasma or red blood cell (RBC) membranes. The FAs most clearly associated with reduced risk for CVD and for total mortality (i.e., death from any cause) are the omega-3 FAs, EPA and DHA, which are typically found in fish like salmon and herring, as well as omega-3 supplements like fish and algal oil.

In a 2018 report that included 2500 participants in the Framingham Offspring Cohort followed for a median of 7.3 years (i.e., between ages ?66 and 73), the baseline RBC EPA + DHA content [the omega-3 index (O3I)] was significantly and inversely associated with risk for death from all causes.

In fact, individuals with the highest Omega-3 Index were 33% less likely to succumb during the follow-up years compared with those with the lowest Omega-3 Index. Similar associations have been seen in the Women's Health Initiative Memory Study, the Heart and Soul Study, and the Ludwigshafen Risk and Cardiovascular Health Study.

The Omega-3 Index measures the amount of EPA and DHA in red blood cell membranes and is a marker of omega-3 status. An optimal Omega-3 Index is 8% or higher, an intermediate Omega-3 Index is between 4% and 8%, and a low Omega-3 Index is 4% and below. Most Americans have an Omega-3 Index below 4%, which puts them a significantly higher risk of early death.

According to researchers in this study, the finding that any FA-based metric would have predictive power similar to that of the well-established standard risk factors was unexpected, and it suggests that RBC FAs--via imperfectly understood mechanisms--somehow reflects an in vivo milieu that consolidates into one measure the impact on the body of all these standard risk factors.

"It is interesting to note that in Japan, where the mean Omega-3 Index is greater than 8%, the expected life span is around five years longer than it is in the United States, where the mean Omega-3 Index is about 5%. Hence, in practice, dietary choices that change the Omega-3 Index may prolong life," said Michael McBurney, PhD, FCNS-SCN, lead researcher in this study. "In the final combined model, smoking and the Omega-3 Index seem to be the most easily modified risk factors. Being a current smoker (at age 65) is predicted to subtract more than four years of life (compared with not smoking), a life shortening equivalent to having a low vs. a high Omega-3 Index."

"The information carried in the concentrations of four red blood cell fatty acids was as useful as that carried in lipid levels, blood pressure, smoking, and diabetic status with regard to predicting total mortality," said Dr. Bill Harris, who was also an author on this study. "This speaks to the power of the Omega-3 Index as a risk factor and should be considered just as important as the other established risk factors, and maybe even more so."

DURHAM, N.C. - The brain's neurons tend to get most of the scientific attention, but a set of cells around them called astrocytes - literally, star-shaped cells - are increasingly being viewed as crucial players in guiding a brain to become properly organized.

Specifically, astrocytes, which form about half the mass of a human brain, seem to guide the formation of synapses, the connections between neurons that are formed and remodeled as we learn and remember.

A new study from Duke and UNC scientists has discovered a crucial protein involved in the communication and coordination between astrocytes as they build synapses. Lacking this molecule, called hepaCAM, astrocytes aren't as sticky as they should be, and tend to stick to themselves rather than forming connections with their fellow astrocytes.

This finding, in studies on mice with the gene for hepaCAM knocked out of their astrocytes, is an important clue in efforts to understand several brain disorders, including cognitive decline, epilepsy and autism spectrum disorders. The work appears June 24 in the journal Neuron.

A rare disorder called megalencephalic leukoencephalopathy (MLC) is also known to be caused by a mutation in the hepaCAM gene, and this work might provide answers about what exactly has gone wrong. MLC is a developmental disorder that grows progressively worse, causing macrocephaly (a large head), swelling of the brain's white matter, intellectual disability and epilepsy.

By removing hepaCAM selectively from astrocytes to see what it does, "we sort of made the cells into introverts," said senior author Cagla Eroglu, an associate professor of cell biology at the Duke University School of Medicine. "They're normally wanting to reach out, but without hepaCAM, they started to hug themselves instead."

"If the astrocyte makes junctions to its neighbors, then you start to have a network," Eroglu said. "To make a functional brain, you need a functional astrocytic network."

The researchers zeroed in on hepaCAM by looking for genes that are highly active in astrocytes and which have been implicated in brain dysfunction. They partnered with another group working on hepaCAM at the University of Barcelona, but that group has been looking at the molecule for its role in regulating chloride signaling channels in astrocytes.

The Duke group found that removing hepaCAM from astrocytes led to a synaptic network that was too easily excited and not as well dampened. "The effect on the inhibitory synapses was the strongest," said first author Katie Baldwin, who recently became an assistant professor of cell biology and physiology at the University of North Carolina at Chapel Hill. "You're putting the inhibition down and the excitation up, so that really could point to a mechanism for epilepsy."

Baldwin, who did this work as a postdoctoral researcher in Eroglu's lab, is planning to further pursue these questions in her new lab at UNC, testing whether hepaCAM-deficient mice behave differently or have changes in learning and memory, or whether they exhibit the stress and social anxiety that are markers of autism spectrum disorders. She said they might also reintroduce the disease-mutation versions of the protein to mice that were born without it to see what effects it has.

"We know hepaCAM is interacting with itself between two astrocytes, but we don't know what it's interacting with at the synapse," Baldwin said. "We don't know if it could be interacting with hepaCAM which is also found in the neurons, or if it could be some other protein that we don't know about yet."

When most Americans think of seaweed, they probably conjure images of a slimy plant they encounter at the beach. But seaweed can be a nutritious food too. A pair of UConn researchers recently discovered Connecticut-grown sugar kelp may help prevent weight gain and the onset of conditions associated with obesity.

In a paper published in the Journal of Nutritional Biochemistry by College of Agriculture, Health, and Natural Resources faculty Young-Ki Park, assistant research professor in the Department of Nutritional Sciences, and Ji-Young Lee, professor and head of the Department of Nutritional Sciences, the researchers reported significant findings supporting the nutritional benefits of Connecticut-grown sugar kelp. They found brown sugar kelp (Saccharina latissima) inhibits hepatic inflammation and fibrosis in a mouse model of diet-induced non-alcoholic steatohepatitis, a fatty liver disease.

They studied the differences between three groups of mouse models. They placed two on high-fat diets but incorporated sugar kelp, a kind of seaweed, into the diet of one. The third group was on a low-fat diet as a healthy control. The group that ate sugar kelp had lower body weight and less adipose tissue inflammation - a key factor in a host of obesity-related diseases - than the other high-fat group.

Consuming sugar kelp also helped prevent the development of steatosis, the accumulation of fat in the liver. Nonalcoholic steatohepatitis (NASH) is a condition often associated with obesity that can cause inflammation and reduced functionality in the liver.

The mice on the sugar kelp diet also had healthier gut microbiomes. The microbiome is a collection of bacteria and other microorganisms in and on our bodies. The diversity and composition of the microbiome are key to maintaining a host of health functions.

"I wasn't surprised to see the data, as we know seaweeds are healthy," Lee says. "But it's still pretty amazing data as this is the first scientific evidence for health benefits of the Connecticut-grown sugar kelp."

This study is the first time researchers have looked at the link between the US-grown sugar kelp and obesity.

"There hadn't been a study about this kind of aspect before," Park says.

Park and Lee saw an opportunity to conduct research on the nutritional science of seaweed, a growing agricultural industry in the United States. They hoped that, by gathering concrete data on the health benefits of sugar kelp, it could encourage people to consume seaweed.

"Consumers these days are getting smarter and smarter," Lee says. "The nutritional aspect is really important for the growth of the seaweed industry in Connecticut."

The researchers specifically used Connecticut-grown sugar kelp, as Connecticut regulates the safety of seaweeds. This is important for monitoring heavy metals that seaweed may absorb from the water.

Most of the seaweed consumed in the US is imported. Park and Lee hope more research on the benefits of locally grown seaweed will prompt consumers to support the industry stateside.

"It's really an ever-growing industry in the world," Lee says.

After completing this pre-clinical study, the researchers now hope to move into clinical studies to investigate the benefits sugar kelp may have for other health concerns. They also want to work on reaching out to people to teach them how to incorporate sugar kelp into their diet.

This work represents a fruitful collaboration between researchers, farmers, and the state.

"Farmers need to know what we're doing is a good thing to help boost their sales," Park says. "We can be a partner."

In collaboration with Anoushka Concepcion, an extension educator with the Connecticut Sea Grant and UConn Extension Program, Park and Lee hope to build stronger partnerships with seaweed growers in Connecticut.

New research from the University of California, Santa Cruz shows how regional shelter-in-place orders during the coronavirus pandemic emboldened local pumas to use habitats they would normally avoid out of fear of humans. This study, published in the journal Current Biology, is part of a growing wave of research working to formally document the types of unusual changes to wildlife movements and behaviors that people around the world reported during pandemic lockdowns.

Golden jackals, for example, were spotted foraging in broad daylight in urban Tel Aviv, Israel, and mountain lions were seen strolling through downtown Santiago, Chile. Urban environments had suddenly become quiet and empty as shelter-in-place orders brought human movement to a grinding halt--an effect some researchers have called the "anthropause." Wildlife seemed to be taking advantage. The new study shows this was certainly true for pumas in the Santa Cruz Mountains. Researchers were able to clearly connect changes in the cats' habitat use with reduced human mobility during shelter-in-place orders.

Chris Wilmers, an environmental studies professor at UC Santa Cruz, led this research. Wilmers is the principal investigator for the Santa Cruz Puma Project, and he has been studying local mountain lion populations for over a decade. In particular, his research uses data from GPS tracking collars placed on wild pumas to show how fear of humans affects mountain lion behavior and ecology. When the pandemic hit, his team was already tracking data from several collared cats, and he recognized a unique research opportunity.

"When the shelter-in-place orders started, it was immediately clear that things were very different," Wilmers said. "You'd go outside and there were very few cars. Entire neighborhoods were completely quiet. So we wondered how this might affect the mountain lion population. Would they respond this quickly to reduced human presence?"

To answer that question, the team analyzed about two years worth of mountain lion tracking data for a set of six collared cats to see where the pumas roamed and what types of habitats they used. Researchers compared these tracks with the distribution of housing density and the geographic boundaries of the "urban edge," which indicates where vehicle and pedestrian traffic is heightened. During regional shelter-in-place orders, they found that cats were significantly more likely to move into or closer to the urban edge. And these changes happened rapidly: within days or weeks of the beginning of COVID-19 lockdowns.

In an effort to hone in on the cause of this change, the team ruled out any influence of natural factors--like topography, vegetation cover, or distance to the nearest water source--that might affect the cats' choice of habitats. They also compared year-over-year tracking data to show that seasonal variability wasn't affecting the results. Pumas do have a strong preference for habitats with lower housing density, but this factor did not change significantly during the study period. The key difference that appeared to be driving the trend of mountain lions moving into urban areas was reduced human mobility during the pandemic.

After regional shelter-in-place orders went into effect on March 17, 2020, local human mobility declined more than 50 percent, according to Apple mobility data, which show the number of navigation requests for driving and walking trips received through Apple Maps. During this time period, when people confined themselves in their homes, the data showed a strong relationship between declining levels of human mobility and pumas' increased willingness to venture closer to or into urban areas.

"We found that they totally relaxed their fear of the urban edge," Wilmers said. "It's not that they weren't scared of cities; they were still scared, but only of high housing density, not the extra impact of human mobility. If you take all the car trips and pedestrian trips and human mobility out of it, then, all of a sudden, mountain lions don't fear the city as much."

Wilmers says this finding helps to build understanding of the unique impacts of human mobility on wildlife. Conservation efforts often focus on the ways that humans are destroying habitats--through development and pollution, for example--but the mere presence of people moving across a landscape also takes a toll on animals that fear humans. And this too is a conservation challenge.

"It's important because our mobility just keeps increasing," Wilmers explained. "In the early part of the 20th century, we got cars, and that really increased our mobility. Now we have things like ride-sharing apps, mountain bikes, and electric bikes, and these are all ways that we're becoming more and more mobile across more types of landscapes. It's an important thing to think about as we try to conserve and manage ecosystems."

Another key point this research illustrates is that fear, or the removal of a source of fear, can bring about rapid changes in animal behavior that ripple out through ecosystems. Ecologists call this concept the "landscape of fear." And the pandemic showed just how integrated into this landscape humans really are. People are usually the ones exerting the influence of fear upon other animals, but there are some things that even we fear.

"Humans have always been the top dog in landscapes of fear, but this study shows that those influences of humans can be reversed relatively quickly by a pathogen, particularly a pandemic-causing pathogen," Wilmers said. "It's interesting from a theoretical perspective, and it's also important in a practical sense because it shows that, not only are pandemics going to have major health consequences for people, but there are also going to be important ecological impacts."

For the past several years, chemical engineer Michelle O'Malley has focused her research on the anaerobic fungi found in the guts of herbivores, which make it possible for those animals to fuel themselves with sugars and starches extracted from fibrous plants. O'Malley's work, reflected in multiple research awards and journal articles, has centered on how these powerful fungi might be used to extract value-added products from the nonedible parts of plants -- roots, stems and leaves -- that are generally considered waste products.

Now, her lab has discovered that those same fungi likely produce novel "natural products," which could function as antibiotics or other compounds of use for biotechnology. The research is described in a paper titled "Anaerobic gut fungi are an untapped reservoir of natural products," published in the Proceedings of the National Academy of Sciences (PNAS).

All living things are equipped with natural defenses to ensure their survival. Microbes often depend on synthesized natural products that act as defenses against environmental threats and allow them to compete with other microbes. Many such natural products have served as the source of antibiotics used to fight disease in humans.

Anaerobic fungi, by definition, do not use oxygen to fuel their production of natural products. Thus, said O'Malley, "It costs them a lot more metabolically to make something than it does an aerobe." Further, anything an anaerobic microbe produces has to be carefully "designed" and extremely efficient, since energy is scarce in the oxygen-free microbes.

O'Malley's lab in 2017 provided the U.S. Department of Energy with several anaerobic gut fungi, which were then sequenced as part of a larger collaboration.

"We started seeing something we didn't expect to find: the building blocks -- biosynthetic gene clusters, or BGCs -- that antibiotics are typically built from," O'Malley said of that work. "BGCs sit near each other on the genome and participate in stepwise chemical reactions. In this case, they are loading a molecule onto an enzyme -- chemically decorating it, if you will -- and then passing it to another enzymatic module and, in this way, making it into an increasingly complex molecule."

That molecular assembly-line process is important, she says, because it emulates how antibiotics are often made. "BGCs could also be of useful for making value-added chemicals, because they have lot of complex chemistry built in," she added. "So, they might be able to be used as drop-in biofuels, as coatings, and as monomers to make novel materials."

But the most important implications, she said, are the antibiotic possibilities. In the paper, lead author Candice Swift, who earned her Ph.D. in O'Malley's lab and is now a postdoctoral researcher at the University of South Carolina's School of Public Health, demonstrates not only that the BGCs are present where they were not expected to be -- anaerobic fungi have never been thought to have antibiotic properties -- they are, even more surprisingly, active and actually making something. "They are transcribed," O'Malley noted.

Swift's analysis suggests that the compounds they found have not been identified previously. "We discovered them, and, based on what is known about these biosynthetic gene clusters, they could be making novel antibiotics," O'Malley said. "We haven't shown that definitively here, but it's one possibility that would make sense, because the fungi exist as kind of minority players in their community, so they probably have some edge or ability that allows them to stick around in the face of overwhelming competition. That's what we think they might be doing. We haven't proven it, but it's an attractive way to look at it."

So, if the anaerobic fungi are producing natural antibiotics, how difficult would it be to translate them into use in humans? "If you identify a novel antibiotic, the key to making that at scale is knowing how it's built," O'Malley explained. "That's a big question. We'll try to address that in a follow-up paper, but if you can figure out the genetic recipe for how they're made, it's straightforward to apply it in another system."

O'Malley said that the scientific community "has become pretty good at making antibiotics, recombinantly or through genetic engineering," and that all, or nearly all antibiotics, are derived from natural products -- either made in nature or inspired by the compounds that nature builds.

The next stage in this research will involve using genetic tools to boost production and isolate the compounds to figure out exactly what compounds are being made. For that work, O'Malley is partnering with other researchers in the BioPolymers, Automated Cellular Infrastructure, Flow, and Integrated Chemistry Materials Innovation Platform (BioPACIFIC MIP), which the National Science Foundation funded last year as a collaboration between UCSB and UCLA.

By Benjamin Boettner

(Boston) - Muscular dystrophies are a group of genetic diseases that lead to the progressive loss of muscle mass and function in patients, with the incurable Duchenne Muscular Dystrophy (DMD), which affects all the body's muscles primarily in boys, being particularly severe. DMD can be caused by more than 7,000 unique mutations in the largest gene of the human genome, which encodes a central protein in muscle fibers. While this astounding number of mutations all variably block muscle function, the affected muscles share another common feature - chronic inflammation.

As chronic inflammation significantly contributes to the speed and severity of muscle degeneration, researchers are pursuing different anti-inflammatory approaches that could be applied to the weakening muscles of DMD patients. Thus far, it has become clear that broad, systemically applied anti-inflammatory therapies cannot reach sufficient efficacies in individual muscles and that, in addition, they can be toxic to patients and increase their risk of infections. To overcome these barriers, locally acting therapies that could be applied on-site at affected muscles would have significant advantages.

Now, a research team at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) led by Wyss Institute Founding Core Faculty member David Mooney, Ph.D., has developed a new approach in which specifically designed anti-inflammatory nanoparticles (NPs) that could be applied locally and selectively to chronically inflamed muscles severely affected or at more immediate risk of deterioration, and maybe difficult to reach with oral therapeutics. In an advanced mouse model of DMD, this strategy increased the volume of muscles covered by myofibers and improved muscle functions by boosting the numbers of infiltrating anti-inflammatory regulatory T cells (Tregs). The findings are published in Science Advances.

A biomaterial-based solution: design and validation

"Using NP-based cytokine delivery, we can create a therapeutic immune status in muscles affected by DMD that targets inflammation as a universal driver of the disease," said Mooney, who leads the Wyss Institute's Immuno-Materials Platform and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. "Given the localized delivery of the highly effective cytokine interleukin-4 (IL-4), this approach could be developed as a stand-alone therapy, or in the future be used in combination with genetic approaches designed to repair specific DMD mutations in patients."

Pro-inflammatory and anti-inflammatory immune cells recruited to wasting muscles and further differentiating in them are thought to play an active game of tug-of-war. Both can temporarily get the upper hand with muscles going through continuous cycles of myofiber injury and regeneration while, in the longer-term, injury always wins. Importantly, the identities and activities of immune cells are controlled by pro- and anti-inflammatory cytokines, immune-modulating molecules that are released by immune or other cells in muscle tissue.

In 2018, Mooney's team had shown that gold nanoparticles (NPs) presenting the anti-inflammatory cytokine interleukin-4 (IL-4) when locally injected into acutely injured muscles of mice, could improve the muscles' strength by 40% compared to control NPs. The NPs were designed such that a core NP of gold was partially coated with a layer of the biocompatible polymer polyethylene glycol (PEG). To the parts of the NP surface revealed by gaps in the coating, IL-4 cytokine molecules were then bound (chemically conjugated), allowing them to be protected by the surrounding PEG, and to remain bioactive for extended times following their injection into muscle tissue and up-take by muscle immune cells.

To study the effects of NPs carrying IL-4 NPs as well as NPs carrying IL-10 (a differently acting anti-inflammatory cytokine) on DMD-affected muscles, the researchers used an existing mouse model, known as Mdx, that carries a specific DMD mutation found in human patients. As muscle degeneration occurs much slower in Mdx mice than in human patients, they developed a microinjury approach in which hind limb muscles of aged Mdx mice were repeatedly injured to accelerate murine disease progression and more closely mimic human disease. In Mdx mice, the microinjury caused chronic DMD-like inflammation and damage that persisted for several weeks.

Invigorating muscles with T cell action

One week after terminating the microinjury procedure, they injected IL-4 NPs (and IL-10 NPs) directly into the chronically injured muscle and after another two weeks analyzed the effects. "Cytokine therapy with IL-4 but not IL-10 conjugated to NPs significantly increased the area in cross-sections covered by muscle fibers and, in living animals, the treated muscles showed a four-fold increase in contraction force and speed (velocity) compared to mice in control groups," said first-author Theresa Raimondo, Ph.D., who performed the work as a graduate student in Mooney's group and now is a Postdoctoral Fellow at MIT.

DMD becomes most life threatening when the diaphragm and cardiac muscles become affected. The team hopes that their strategy one day could help improve breathing and heart function in patients, although future studies will have to assess this possibility.

"Interestingly, we could chalk up the regenerative effects to a specific increase in Tregs, an immunosuppressive T cell type that was known to counteract inflammatory processes in muscles weakened by DMD."

The team observed a 50% increase in the number of Tregs in chronically injured muscles of aged Mdx mice while the numbers of other types of immune cells, including neutrophils, dendritic cells, natural killer cells, monocytes, and macrophages remained unchanged with their NP-based cytokine therapy.

Especially macrophages in their anti-inflammatory state called M2 had also been suggested to contribute the restoring muscle strength and function in mouse models of DMD, and were found previously by Mooney's team to be key to repairing acutely injured muscles in normal mice. However, in the chronically inflamed muscles of the advanced Mdx model that were targeted with NP-based IL-4 therapy in the new study, M2 macrophages did not significantly contribute to the therapeutic effect. "Our combined findings highlight that the same cytokine therapy can achieve very different immunological outcomes with therapeutic effects on muscles dependent on the type of inflammation that is present," said Mooney.

"This approach developed by Dave Mooney's group at the Wyss' Immuno-Material Initiative could be developed as an alternative, strategically applied solution for treating patients with Duchenne Muscular Dystrophy whose loss of muscle mass and function cannot be effectively stopped by any other means. The same basic principle of NP-based cytokine therapy could also have potential for a variety of other muscle disorders where inflammation is a major force," said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at SEAS.

PRESS CONTACT

Wyss Institute for Biologically Inspired Engineering at Harvard University
Benjamin Boettner, benjamin.boettner@wyss.harvard.edu, +1 617-432-8232

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ITHACA, N.Y. - Tossing worn-out solar panels into landfills may soon become electronics waste history.

Designing a recycling strategy for a new, forthcoming generation of photovoltaic solar cells - made from metal halide perovskites, a family of crystalline materials with structures like the natural mineral calcium titanate - will add a stronger dose of environmental friendliness to a green industry, according to Cornell University-led research published June 24 in Nature Sustainability.

The paper shows substantial benefits to recycling perovskite solar panels, though they are still in the commercial development stage, said Fengqi You, the Roxanne E. and Michael J. Zak Professor in Energy Systems Engineering in the College of Engineering.

"When perovskite solar panels reach the end of their useful life, how do we deal with this kind of electronic waste?" said You, also a faculty fellow at the Cornell Atkinson Center for Sustainability. "It is a new class of materials. By properly recycling it, we could potentially reduce its already low carbon footprint.

"As scientists design solar cells, they look at performance," You said. "They seek to know energy conversion efficiency and stability, and often neglect designing for recycling."

Last year, You and his laboratory found that photovoltaic wafers in solar panels containing all-perovskite structures outperform photovoltaic cells made from state-of-the-art crystalline silicon, and the perovskite-silicon tandem - with cells stacked like pancakes to better absorb light - perform exceptionally well.

Perovskite photovoltaic wafers offer a faster return on the initial energy investment than silicon-based solar panels because all-perovskite solar cells consume less energy in the manufacturing process.

Recycling them enhances their sustainability, as the recycled perovskite solar cells could bring 72.6% lower primary energy consumption and a 71.2% reduction in carbon footprint, according to the paper, "Life Cycle Assessment of Recycling Strategies for Perovskite Photovoltaic Modules," co-authored by Xueyu Tian, a doctoral student at Cornell Systems Engineering, and Samuel D. Stranks of the University of Cambridge.

"Lowering the energy needed to produce the cells indicates a significant reduction of energy payback and greenhouse gas emissions," said Tian.

The best recycled perovskite cell architecture could see an energy payback time of about one month, with a carbon footprint as low as 13.4 grams of carbon dioxide equivalent output per kilowatt hour of electricity produced. Without recycling, the energy payback time and carbon footprint of new perovskite solar cells show a range of 70 days to 13 months, and 27.5 to 158.0 grams of carbon dioxide equivalent throughout their life cycles.

Today's market-leading silicon photovoltaic cells can expect an energy payback period of 1.3 to 2.4 years, with an initial carbon footprint between 22.1 and 38.1 grams of carbon dioxide equivalent emissions per kilowatt hour output.

"Recycling makes perovskites outcompete all other rivals," Tian said.

Informed state and federal policies, along with recycling infrastructure development strategies, can further mitigate the environmental impacts in making photovoltaic solar cells.

Said You: "The real value of an effective green perovskite solar panel industry may rely on a recycling program."