Culture

The brain jiggles when the heart beats, and now, researchers have found a way to use that motion to better study the differences between types of neurons. In a study appearing March 10 in the journal Cell Reports, researchers find that by analyzing the changes in the waveforms they record from neurons during a heartbeat, they can more accurately classify the different types of neurons in the human brain. This work, they say, could help us better understand how the different types of cells that exist in the brain interact together to produce cognition and behavior.

"We were recording neurons from the brain of human patients implanted with electrodes for neurosurgical procedures, and we lined up the neural activity to the heartbeat and saw that many neurons changed their firing pattern every time the heart beats," says Clayton Mosher (@ClaytonPMosher), of Cedars-Sinai Medical Center, who is the joint first author of the study with Yina Wei, of the Allen Institute. "We were like, 'Okay. This is surprising,'"

But as the team zoomed in more, they realized that the neurons weren't firing in a different pattern; instead, the brain was jiggling. For every heartbeat, the brain pulses, and the neurons shift their place slightly within the skull. The scientists estimate that the neurons shift about three micrometers, which is less than the width of a hair, during a heartbeat. The appearance of a difference in neuronal firing was created by this movement.

"We started from something that many people viewed as a result of brain motion rather than neural activity. They consider it noisy. They consider it as a limitation of their experiment," says Costas Anastassiou, of the Allen Institute, who is the senior author of the study together with Ueli Rutishauser, of Cedars-Sinai Medical Center. "What we were able to show is that if used it in a smart way, this naturally occurring motion of the brain can tell us much more about the identity of the cells we're recording from. This is because measuring the activity of the same neuron from different locations in the brain provides additional information about the neuron."

Conventionally, scientists classify neurons based on their waveform, a characteristic pattern of electrical activity that each neuron emits every time it becomes active, i.e. when it "spikes." The shape of each neuron's waveform is different. By examining the width of the waveform, scientists can reliably categorize neurons into two types: those with narrow and those with broad waveforms.

Now, the tiny brain motion caused by the heartbeat allows scientists to measure the waveform shape more accurately. As the distance between a neuron and the electrode changes, the measured waveform changes as well. By measuring these changes, the team showed that they can differentiate between three different classes of neurons in the human hippocampus: narrow spike (NS), broad spike one (BS1), and broad spike two (BS2). And each class has different firing properties: the researchers found that BS1 neurons coordinate their activity with gamma waves, whereas BS2 neurons coordinate their activity with theta waves.

"Gamma and theta waves are patterns of activity in the brain that are highly relevant to cognition. We know, for example, that memory and learning are very closely linked with theta oscillations. We know that attention is closely linked with gamma oscillations," says Anastassiou.

"At the end of the day, to understand how the brain works, we need to understand what different types of cells exist in the brain, and how these cell classes interact together to produce cognition and behavior," he says. "One needs to be able to bridge across scales to say how the microscopic world gives rise to this behavioral phenomenon happening in the macroscopic world. Our work reveals, for the first time, how to achieve such a bridge between scales for the human brain."

One of the challenges in neuroscience is that there is often a difference between how neurons behave in living humans and how they behave when investigated in isolation in a brain slice. Through recordings from human brain tissue, the researchers were able to construct single-cell models that simulate the biophysical features and morphology of real neurons. The model bridges the in-vivo brain and ex-vivo brain slice recordings to serve as a novel tool to categorize neurons. The computational models of human neurons can be used to better understand the signals we record from live human beings implanted with electrodes.

"Ultimately, what we want to understand is, one, how different types of neurons in the human brain contribute to cognition and behavior," says Mosher. "The second goal is to investigate how the heartbeat and breathing, in turn, influences behavior or cognition."

Texans who are college-educated, live in suburban or urban areas, have higher median incomes and are ethnically white are less likely to vaccinate their children, according to analysis by researchers at The University of Texas at Austin. The findings could help public health officials identify pockets of low vaccination rates where communities within the state are at higher risk for an outbreak of vaccine-preventable diseases such as measles.

In a paper published today in the journal PLOS Medicine, professor of integrative biology Lauren Ancel Meyers, a computational epidemiologist, and her team at UT Austin compared publicly available census data with the number of conscientious vaccination exemptions from public, private and charter school systems across Texas. The state is one of 15 to allow families who cite a philosophical objection to vaccines to opt out of immunizations for their children that are otherwise required for enrolling in school. A total of 45 states and Washington, D.C., allow religious objections to immunizations.

"The study not only provides a window into local vaccination patterns throughout Texas, but also allows us to make predictions," Meyers said. "If you don't have data on the vaccination rate for a given community, you can use demographic factors to predict outbreak risks for vaccine-preventable diseases."

Researchers consider vaccination exemption rates of 3% or higher in a school or school district to be the threshold for high risk of an outbreak of vaccine-preventable illness. A growing number of schools exceed that threshold in Texas. Between the 2012-2013 school year and the 2017-2018 school year, the percentage of school districts reporting high-risk levels of exemptions doubled in public school districts across the state, rising from 3% to 6%. High-risk private schools increased from 20% to 26%, and charter schools increased from 17% to 22%.

The study examined the top 10 metropolitan areas in Texas, including rural, suburban and urban communities within each area. Suburban and higher-income urban communities were more likely to have high vaccination exemption rates than rural counties, the study found. Austin, Dallas-Fort Worth and Houston were the cities with the highest risk of vaccine opt-outs. Areas with higher percentages of young children, ethnically white people and people with a bachelor's degree were more likely to have higher vaccination exemption rates.

On the flip side, researchers found that counties with lower median income and a higher percentage of people who spoke a non-English language at home were more likely to have a lower vaccine opt-out rate.

"We wanted to identify potential pockets of hidden risk throughout Texas stemming from declining childhood vaccination rates," Meyers said.

To do this, Meyers and colleagues took a more detailed look at the data. Prior studies looked at average exemption rates within counties and concluded that most Texas counties did not cross the 3% exemption rate. By instead tracking the number of individual schools and districts above this threshold, the team identified unseen pockets of risk. Travis County, for instance, has a 2.8% conscientious exemption rate. But using her more fine-tuned model, Meyers was able to predict pockets within Travis County where the vaccination exemption rate was higher than 3%.

"This study allows us to detect potential hot spots at a finer geographic scale," she said. "The increasing numbers of exemptions are already alarming. In addition, the clustering of unvaccinated children in tight communities only amplifies the risk of an outbreak."

Similar studies have been performed in other states, such as California. Meyers' study was the first to look at Texas, which is considered a high-risk state for an outbreak of vaccine-preventable illness, at such a granular level. Meyers and her team estimate that 5% of public schools in metropolitan areas of Texas, 28% of private schools and 22% of charter schools are at risk for an outbreak.

The study did not offer any clues about why some demographic groups are opting out of vaccinating their children at such a high rate.

Large ecosystems, such as the Amazon rainforest, will collapse and disappear alarmingly quickly, once a crucial tipping point is reached, according to calculations based on real-world data.

Writing in Nature Communications (10.1038/s41467-020-15029-x), researchers from Bangor University, Southampton University and The School of Oriental & African Studies, University of London, reveal the speed at which ecosystems of different sizes will disappear, once they have reached a point beyond which they collapse - transforming into an alternative ecosystem.

For example, once the 'point of no return' is reached, the iconic Amazon rainforest could shift to a savannah-type ecosystem with a mix of trees and grass within 50 years, according to the work.

Some scientists argue that many ecosystems are currently teetering on the edge of this precipice, with the fires and destruction both in the Amazon and in Australia.

"Unfortunately, what our paper reveals is that humanity needs to prepare for changes far sooner than expected," says joint lead author Dr Simon Willcock of Bangor University's School of Natural Sciences.

"These rapid changes to the world's largest and most iconic ecosystems would impact the benefits which they provide us with, including everything from food and materials, to the oxygen and water we need for life."

What can be done to slow these collapses?

Ecosystems made up of a number of interacting species, rather than those dominated by one single species, may be more stable and take longer to shift to alternative ecosystem states. These provide opportunities to mitigate or manage the worst effects, say the authors. For example, elephants are a termed a 'key stone' species as they have a disproportionately large impact on the landscape - pushing over trees, but also dispersing seeds over large distances. The authors state that the loss of key stone species, such as this, would lead to a rapid and dramatic change in the landscape within our lifetime.

"This is yet another strong argument to avoid degrading our planet's ecosystems; we need to do more to conserve biodiversity," says Dr Gregory Cooper, School of Oriental & African Studies, University of London.

Prof John Dearing from Geography and Environment at Southampton University says:

"We intuitively knew that big systems would collapse more slowly than small ones - due to the time it takes for impacts to diffuse across large distances. But what was unexpected was the finding that big systems collapse much faster than you might expect - even the largest on Earth only taking possibly a few decades."

Studying gamma ray emissions from phenomena like supermassive black holes allows astrophysicists to better conceptualize the behavior of matter under extreme conditions. Although dark matter is thought to account for roughly a quarter of all energy content in the cosmos, its relationship with gamma rays is mysterious. Now, Ammazzalorso et al. have found the first direct cross-correlation between gamma rays and matter in the Universe. They used gamma ray data from Fermi Large Area Telescope and mapped it with weak gravitational lensing -- a method used obtain the mass distribution of objects. The results could improve particle physicists' understanding of the nature of dark matter and whether dark matter can be a source of gamma ray emissions from space.

INDIANAPOLIS - It is common for critically ill patients on life support to develop delirium, a form of acute brain failure for which no effective treatment is known. A study from Indiana University School of Medicine and Regenstrief Institute researchers reports that music appears to decrease delirium in patients on mechanical ventilators in the intensive care unit (ICU).

In the study, critically ill individuals who listened to slow-tempo, relaxing music (60 to 80 beats per minute) had decreased need for sedatives, fewer days of delirium and were more awake -- enabling them to receive physical therapy earlier. These results are encouraging and a larger clinical trial is currently underway.

Mechanically ventilated patients -- more than a million adults annually in the United States -- are at increased risk for delirium, which is associated with prolonged ICU stays, higher healthcare costs and increased mortality. The intubated patient experiences pain, anxiety and physiologic stress for which they usually are treated with drugs, which can contribute to delirium. This perpetuates a cycle of pain, anxiety, sedation and delirium.

"Like kidney or heart failure, individuals can develop brain failure, but there is no treatment equivalent to dialysis or the ventilator for brain failure, a condition which can adversely affect an individual's personality and quality of life for years," said Sikandar Khan, D.O., M.S., IU School of Medicine assistant professor of medicine and Regenstrief Institute research scientist, who led the new study. "Recent studies by our group and others have shown that drugs, including commonly prescribed antipsychotics, do not treat delirium or reduce its severity, so we desperately need a non-pharmacologic treatment. Our pilot study shows that music may hold promise to help save patients' brains and allow them to experience less stress while critically ill."

Existence of delirium and delirium severity were assessed twice daily in an Eskenazi Health medical-surgical ICU using the CAM-ICU-7, short for Confusion Assessment Method for the Intensive Care Unit 7, a tool developed by Regenstrief Institute and IU School of Medicine clinician-researchers.

Additionally, the new study is the first to determine the acceptability of music by patients on mechanical ventilators and the feasibility of administering music by non-specialists. Patients who listened to the slower-tempo, relaxing music two hours per day needed less sedation and had more delirium free days. ICU nurses could easily place noise-cancelling headphones and audio players with patients.

The researchers divided ICU patients on mechanical ventilators into three groups. Patients were randomized to (1) slow tempo playlists consisting of piano, guitar, Native American flute sounds and classical music; (2) patient preference for the selection of music (as conveyed by surrogates) or (3) an audio book. Patients in the audiobook arm of the study were further randomized to hear a reading of "Treasure Island," the Harry Potter series, or Dr. Seuss' "Oh the Places You'll Go!" All three audiobooks were chosen for readability, broad appeal, quality of narration and high ratings on commercial websites.

Eighty percent of the patients in the study rated the music enjoyable, duration appropriate and indicated that they liked receiving sessions twice a day. Patients noted music had made them feel more normal and calm as well as giving them a sense of control. Slow-tempo music, which had a significantly greater effect than music selected by patient preference, was also more highly favored by study participants.

By contrast, no matter which of the three books they heard while on the ventilator, patients rated audiobooks poorly, with lower acceptance than music of any type.

"Our work is novel in that we explored the effect of music on critically ill, mechanically ventilated adults age 18 and older, a very different group for whom music and delirium has not been previously studied," added Dr. Sikandar Khan. "It's the first study of its type based on science -- in previous work on biomarkers we had shown that slow-tempo music yielded less stress hormones in blood -- and science won."

"Decreasing Delirium through Music (DDM): A Randomized Pilot Trial," is published in the American Journal of Critical Care. Authors in addition to Dr. Sikandar Khan are Chenjia Xu, PhD; Russell Purpura, M.D.; Sana Durrani, MBBS; Heidi Lindroth, PhD, R.N.; Sophia Wang, M.D.; Sujuan Gao, PhD; Annie Heiderscheit, PhD; Linda Chlan, PhD, R.N.; and Regenstrief Institute Research Scientists Malaz Boustani, M.D., MPH and Babar A. Khan, M.D., M.S. The work was supported by a Regenstrief Innovations award.

Dr. Babar Khan and Dr. Chlan are the primary investigators (PIs) and Dr. Sikandar Khan is an investigator of an ongoing randomized controlled clinical trial that is evaluating the effectiveness of exposure to slow-tempo classical music versus simple noise cancellation in decreasing delirium in older adults. The five-year project is supported by the National Institutes of Health's National Institute on Aging and National Eye Institute.

World Delirium Awareness Day is March 11, 2020.

New international research by Woods Hole Oceanographic Institution (WHOI) and colleagues has found a marked change in the Indian Ocean's surface temperatures that puts southeast Australia on course for increasingly hot and dry conditions.

The work led by The Australian National University (ANU) and the ARC Centre of Excellence for Climate Extremes has a silver lining, helping to improve our understanding of climate variations and the management of risk caused by Indian Ocean variability.

Lead researcher Professor Nerilie Abram said the phenomenon her team studied, known as the Indian Ocean Dipole (IOD), was a big player in the severe drought and record hot temperatures in Australia last year.

"The 2019 event, known as a positive Indian Ocean Dipole, was a big one," said Abram from the Research School of Earth Sciences and the Centre of Excellence for Climate Extremes at ANU. "It cut off one of the major sources for southern Australia's winter and spring rainfall, and set up the extremely hot and dry conditions for the terrible fires that ravaged Australia this summer."

"The Indian Ocean Dipole does not only affect Australian climate, but is also linked to floods in East Africa, changes in the Indian monsoon, and droughts and wildfires in Indonesia--areas that experienced unusual climate conditions during the record 2019 event", added Caroline Ummenhofer, a WHOI climate scientist and co-author of the study.

The new research published in Nature reveals that these historically rare events have become much more frequent and intense during the 20th Century, and this situation is expected to worsen if greenhouse gas emissions continue to rise. The research team, which involved scientists from institutions in Australia, the United States, Indonesia, Taiwan and China, used coral records from the eastern equatorial Indian Ocean to reconstruct Indian Ocean Dipole variability over the last millennium with unprecedented precision.

"Historically, strong events like the one we saw in 2019 have been very rare," Abram said. "Over the reconstruction beginning in the year 1240, we see only 10 of these events, but four of those have occurred in just the last 60 years."

The research highlighted that the Indian Ocean can harbour events that are even stronger than the extreme conditions seen in 2019. In 1675, an event occurred that was up to 42 percent stronger than the strongest event observed so far during the instrumental record, which was in 1997. The dire impacts of this older severe event can be seen in historical documents from Asia.

"Having this new extended information of Indian Ocean Dipole events recorded by corals going back centuries is particularly valuable, as few long-term observations exist from the Indian Ocean," said Ummenhofer. "These new records help us understand how the Indian Ocean interacts with ENSO in the Pacific and can ultimately benefit Indian Ocean rim countries be better prepared for future climate risks."

Nearly 94% of defendants in Cuyahoga County drug court have been exposed to trauma and many suffer from symptoms of post-traumatic stress disorder (PTSD), according to a new Case Western Reserve University study.

"These findings tell us that we need to not only treat the disease of addiction, but also the underlying mental-health issues that so often coincide with them," said Margaret Baughman, co-author of the study and a senior research associate at the Center on Trauma and Adversity at the university's Jack, Joseph and Morton Mandel School of Applied Social Sciences.

Researchers surveyed nearly 300 people going through the substance use treatment dockets at the Cuyahoga County Common Pleas Court and the Cleveland Municipal Court.

The researchers analyzed lifetime, childhood, and recent exposure to trauma and PTSD symptoms for the total sample, as well as by gender. They defined exposure to trauma as incidents that include physical violence, life-threatening accidents, sexual assault and/or being present when someone is killed.

PTSD symptoms manifest in many ways, including nightmares or unwanted memories of the trauma, avoidance of situations that bring back memories of the trauma, heightened reactions, anxiety or depression.

The study also found that:

70% of those who experienced a "serious disaster" stated it happened before turning 18.

83% reported being sexually assaulted in their lifetimes--75% for men and 85% for women.

44% of men in drug court who reported trading sex for money or shelter did so before the age of 18, as opposed to 29% for women before the age of 18.

Researchers said these findings identify a need for increased trauma-informed care--and possibly specialized, gender-specific care. It's well-documented that drug courts successfully reduce rates of recidivism for participants, they said, but a gap remains for mental-health screenings.

"We think that trauma-informed care should be a part of the important work being done in these courts," said co-investigator Krystel Tossone, also a senior research associate at the Trauma Center. "We know that if we don't treat the underlying trauma issues, the courts are going to see many of these people again and again."

Adding trauma-informed social workers and peer supporters to the court process might make sense, Tossone suggested.

"Many tend to view substance abuse and mental health in separate silos," Baughman said. "But from the beginning, we should be aggressively blend treating addiction and mental-health issues."

A new study published in the Journal of Nutrition Education and Behavior (JNEB) builds on years of previous research studies and demonstrates the value of family meals. This study showed that more frequent family meals were associated with better dietary outcomes and family functioning outcomes. While Americans celebrate the month of March as National Nutrition Month, these findings underscore the myriad benefits advanced by family meals advocates over the past few years and punctuate the official launch of the Family Meals Movement.

"This study employed a comprehensive approach to explore the direction and magnitude of the relationship between exposure to family meals and dietary and family functioning outcomes in children," said lead study author, Shannon M. Robson, PhD, MPH, RD, an assistant professor in the Department of Behavioral Health and Nutrition and a Principal Investigator of the Energy Balance and Nutrition Laboratory at the University of Delaware. "A systematic review as well as a meta-analysis, when statistically appropriate, of all relevant studies published in a peer reviewed journal in English prior to December 2018 was conducted." A link to the study can be found here: https://www.jneb.org/article/S1499-4046(19)31154-6/fulltext

There are two notable findings to this study:

1. Family meals improve fruit and vegetable consumption - overwhelmingly, studies showed a positive relationship between family meal frequency and fruit and vegetable intake when examined separately, but also when fruit and vegetable intake were combined.

2. Family meals improve family functioning - nearly all the studies included in the systematic review and meta-analysis demonstrated a positive relationship between family meal frequency and measures of family functioning. Family functioning is defined as family connectedness, communication, expressiveness, and problem-solving.

"There are thousands of individual studies that examine the impact of family meals on nutrition and family behavior, but this new meta-analyses looks at the relationship between family meal frequency and family functioning outcomes," said David Fikes, executive director of the FMI Foundation, the organization that provided a research grant for this study. "It is particularly fitting that as we celebrate National Nutrition Month, we can confirm that family meals are a valuable contributor of improved nutrition and family functioning. This compelling evidence energizes us to expand our National Family Meals Month efforts to a year-long Family Meals Movement."

For the past five years, the FMI Foundation has driven National Family Meals Month™ which has been observed each September. The campaign has encouraged Americans to strive for just one more family meal per week at home and energized more than 600 partners - food retailers, suppliers, collaborators, media and celebrities - to support the campaign. A Harris Poll national tracking study impressively substantiates that mealtime behaviors are changing because of this initiative with 36% of Americans who saw the campaign cooking more meals at home and eating together more often as a family.

"Even more impressive than the positive behavior changes we have seen over the past five years," Fikes continued, "is that 89% of Americans believe it's important for families to have as many family meals as possible each week, and 84% are willing to commit to doing so throughout the year. This kind of interest and commitment has motivated us to expand National Family Meals Month to the ongoing Family Meals Movement."

The FMI Foundation encourages Americans to join the Family Meals Movement by pledging to share one more family breakfast, lunch or dinner at home per week using items from the grocery store. Shoppers can post pledge photos, mealtime pictures, favorite recipes, shopping tips or even a selfie wearing a favorite oven mitt with the hashtag #FamilyMealsMovement. In addition, the FMI Foundation has developed a website, http://www.FamilyMealsMovement.org with consumer tips and links to numerous partners committed to helping consumers achieve their increased family meals goal.

For the first time, an international collaboration of researchers have succeeded in creating a complete overview of all pain conditions in the face, mouth and jaw and classifying them in the same way.

This means that medical doctors and dentists will have a common language and the same understanding of this pain. In turn, this will benefit the diagnosing of patients and thus the patients themselves, says professor of pain research Peter Svensson from the Department of Dentistry and Oral Health at Aarhus University, Denmark.

He has worked with pain researchers from all over the world to bring the overview together.

"We prevent misunderstandings when we use the same criteria, and this provides a better basis for making the right diagnosis. Patients benefit directly because a correct diagnosis is the basis for correct treatment," says Peter Svensson.

To understand the significance of the classification, Peter Svensson uses the example of the concept of 'heart disease', which covers many diagnoses.

"I don't imagine anyone would be satisfied if they were diagnosed with 'heart disease', as there are many specific variants of heart disease and they require different treatment. In the same way, pain in the mouth, jaws and face, which we call orofacial pain, isn't one type of pain, but covers many different types of pain that are also treated differently," he adds.

The inspiration for the combined classification of orofacial pain comes from a similar classification of headaches. Peter Svensson elaborates:

"The headache classification was an important reason for improving and strengthening research into the background for and treatment of headaches, and we hope that the international classification will do the same for the professional environments within orofacial pain."

It is estimated that twenty per cent of the population suffer from chronic pain, and for many sufferers, this pain is severely disabling. "The recognition of pain as a disease followed by a systematic registration of pain conditions is therefore of great importance for research, which is becoming more targeted," says Peter Svensson.

"Research into orofacial pain has lagged behind in general pain research. The new classification - the common language for pain - can contribute to new studies which identify more precisely how common orofacial pain is and the factors which come into play when people are afflicted by chronic orofacial pain," he says.

The classification has just been published as the ICOP International Classification of Orofacial Pain in the professional journal Cephalalgia and builds on the previous classification work that led to chronic pain going from being symptomatic of a disease to being a disease in itself.

According to Peter Svensson, being included in the WHO's manual of diseases is a seal of approval, and he anticipates that the new classification will have just as much value.

ITHACA, N.Y. - Muscle repair is a crowded, complicated business. Many different types of cells are bumping around, chattering and trying to coordinate with each other as they work to regenerate new tissue.

A team of Cornell researchers led by Ben Cosgrove, assistant professor in the Meinig School of Biomedical Engineering, used a new cellular profiling technology to probe and catalog the activity of almost every kind of cell involved in muscle repair. They compiled their findings into a "cell atlas" of muscle regeneration that is one of the largest datasets of its kind. This resource provides a comprehensive picture of the many intricate cellular interactions in tissue self-repair and may potentially lead to better rehabilitation strategies and support for patients recovering from muscle injuries.

The team's paper, "Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration," published March 10 in Cell Reports.

Cosgrove worked with Cornell's Biotechnology Resource Center to use single-cell RNA sequencing to analyze the gene expression signatures in thousands of individual cells, all taken from the actively regenerating muscles of mice - including the rare muscle stem cells that drive the repair process. Cosgrove also collaborated with Iwijn De Vlaminck, the Robert N. Noyce Assistant Professor in Life Science and Technology in the Meinig School of Biomedical Engineering. Together, they applied new algorithms to filter the extensive collection of molecular information.

The researchers profiled and collected approximately 35,000 individual cells. The resulting atlas is a benchmark technical resource for researchers studying skeletal muscle tissue.

"Because we have such a large dataset, it helps us frame a number of hypothesis-driven questions about not only which cells are involved, but how they are communicating with each other," said Cosgrove. "This resource enabled us to ask 'What molecular signals are one type of cells sending to the other cells within the process of muscle repair?'"

Unlike a road atlas that uses spatial coordinates, this atlas is more of a "laundry list of the key cell players," Cosgrove said, itemizing their similarities and differences, with 15 unique cell types in muscle tissue. This collection emphasizes how much heterogeneity exists within each cell type, a range of diversity that led the researchers to pursue the sources of specific molecular variations that might be otherwise overlooked.

"Because this approach allows us to look closely at one cell at a time, we could consider and evaluate the subtle differences even within a similar group of the same cells," he said.

Cosgrove's lab has already put the atlas to good use by identifying how a class of proteins called syndecans play a pivotal role in enabling muscle stem cells to make a binary choice during the process of muscle regeneration. As they are dividing, the stem cells chose either to replenish the stem cell population, or they turn into the mature myofiber cells that replace damaged muscle tissue.

"We took this huge atlas and partitioned it down to the stem cells. And then we organized the stem cells in a way that gives us a framework to think about variation and the choices the cells are making," Cosgrove said.

Their findings show that syndecan-related variations may help direct how muscle stem cells respond to signals from their neighboring cells and which outcome they chose.

"Now that we know more about what is happening in the healthy, normal adult repair process, we can ask 'How do the cellular players get misallocated and misactivated in the disease settings?'" Cosgrove said.

Cosgrove's group is currently applying this approach to look at muscle repair deficiency in aging and muscular dystrophy.

Research at North Carolina State University shows that the CRISPR-Cas system can be used to effectively target and eliminate specific gut bacteria, in this case Clostridioides difficile, the pathogen that causes colitis - a chronic, degenerative disease of the colon.

In a proof-of-concept study published in the journal mBio, researchers were able to show pathogen reductions in experiments conducted both on the lab bench and in mice.

Microbiologists from two different NC State colleges teamed with NC State startup company Locus Biosciences to test the effectiveness of using a virus called a bacteriophage to carry a programmable CRISPR to specifically target and eliminate C. difficile bacteria, a search-and-destroy mission that holds promise for human gut health.

"We wanted to engineer phages with self-targeting CRISPR payloads and deliver them to the gut of an organism of choice - in this case a mouse - in order to have a beneficial impact on host health and to prevent disease," said Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor of Food, Bioprocessing and Nutrition Sciences at NC State and co-corresponding author of a paper describing the research.

Co-corresponding author Casey M. Theriot, an assistant professor of infectious disease at NC State, said that use - and overuse - of antibiotics increases susceptibility to C. difficile infection, as antibiotics wipe out both good and bad bacteria in the gut. Relapses occur in some 30% of human patients treated with a standard antibiotic to eliminate C. difficile.

"We need to target the precise pathogen without disturbing the rest of the microbiome, and that's what this approach does," she said.

CRISPR technologies have been used to precisely remove or cut and replace specific genetic code sequences in bacteria. The CRISPR method used in this study involved Cas3 proteins that acted like an arcade game Pac-Man, Barrangou said, chomping C. difficile bacteria and causing extensive DNA damage.

In the lab, the CRISPR-Cas systems effectively killed C. difficile bacteria. After that, the researchers tested this approach in mice infected with C. difficile. Two days after the CRISPR treatment, the mice showed reduced C. difficile levels, but those levels grew back two days later.

"C. difficile is really difficult to work with, hence its name," Theriot said.

"This was a positive first step in a long process," Barrangou said. "The results of using phages to deliver CRISPR payloads open up new avenues for other infectious diseases and beyond."

Next steps include retooling the phage to prevent C. difficile from returning after the initial effective killing. The researchers said that future work will also involve developing a library of different phages for various C. difficile strains.

An avocado a day improves the ability to focus attention for overweight or obese adults, Illinois researchers found in a new study.

An avocado a day improves the ability to focus attention for overweight or obese adults, Illinois researchers found in a new study.

CHAMPAIGN, Ill. -- A diet including daily avocado consumption improves the ability to focus attention in adults whose measurements of height and weight are categorized as overweight or obese, a new randomized control trial found.

Researchers at the University of Illinois at Urbana-Champaign conducted the 12-week study, published in the International Journal of Psychophysiology.

"Previous work has shown that individuals with overweight and obesity are at higher risk for cognitive decline and dementia in older age," said kinesiology and community health professor Naiman Khan, who led the study. "We are interested in whether dietary approaches may have benefits for cognitive health, especially in midlife."

The Hass Avocado Board and the U.S. Department of Agriculture's National Institute of Food and Agriculture supported this work.

Avocados are high in lutein, a dietary component associated with cognitive benefits. Though avocado consumption's benefits have been studied in older adults and children, no randomized controlled trials had studied its cognitive effects on adults with overweight or obesity, despite 70% of the American adult population falling into that category, said graduate student Caitlyn Edwards, the first author of the study.

In the new study, the researchers provided 12 weeks of daily meals to 84 adults with overweight or obesity. The meals were identical in calories and macronutrients, but one group's meals included a fresh avocado every day, while the control group had no avocado in their meals.

At the beginning and end of the study, the participants completed three cognitive tests to measure attention and inhibition. In addition, the researchers measured lutein levels in the participants' serum and in their retinas, which is associated with the lutein concentration in the brain.

They found that the participants whose diets included avocados improved their performance on one of the cognitive tests, called the Flanker task, which measures attentional inhibition - the ability to maintain focus on the task at hand even in the face of distraction. However, there was no difference in the other two cognitive tests.

"It could be that nutrients in avocados have a specific action in the brain that supports the ability to do this task in particular, or they could be more beneficial for certain cognitive abilities over others," Khan said. "It's also possible that with a longer study or different tests, we could see other effects. Other studies have found broader effects in other populations, so it is interesting to see a more specific benefit for this population."

Another unexpected finding was that, while the participants who ate avocados had higher levels of lutein at the end of the study, the changes in lutein levels were not correlated with their cognitive changes.

"Avocados also are high in fiber and monounsaturated fats. It is possible that these other nutrients may have played a role in the cognitive effects we saw, but we focused on the lutein in our analyses," Edwards said. "Future analyses may focus on other nutrients found in avocados, or avocado consumption's impact on other measures such as weight status, inflammation and potential changes in the microbiome."

Although this study focused on avocados, other dietary sources of lutein, fiber and unsaturated fats - such as green leafy vegetables or eggs - also have potential cognitive and health benefits. The researchers say their study shows that small dietary changes, such as eating avocados, can have measurable impacts on cognitive performance, even when other health behaviors remain the same.

"Our mission is to give people options. There are multiple ways people can eat to optimize brain health," Khan said. "What we're learning is that avocados may be one of those fruits that may be neuroprotective in certain ways. This work provides some evidence behind one option people have from a plethora of healthful foods that we can consume."

Pancreatic cancer is predicted to become the second leading cause of cancer-related deaths by 2030. However, recent developments in staging and treatment provide options to improve the long-term survival rate for an otherwise devastating diagnosis.

Today, new research published in Annals of Surgery from the University of Colorado Department of Surgery at the Anschutz Medical Campus offers a roadmap to new guidelines for physicians in prioritizing treatments and improving outcomes through surgery.

The study suggests a new concept of resectability and identifies objective pre-operative prognostic factors that can predict long-term survival of patients affected by pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer.

"Our research suggests that a new concept of resectability should be considered that is meant to reflect the biology of the tumor and response to chemotherapy," said Marco Del Chiaro, MD, PhD, FACS, Chief of Surgical Oncology and Director of the National Pancreas Foundation Center of Excellence at the Anschutz Medical Campus. "Therefore, this will partially overcome the existing guidelines that are mostly based on tumor anatomic features. Tumor anatomic features are extremely subjective and vary between center to center and surgeon to surgeon."

In the study, researchers analyzed nearly 8,000 patients who underwent pancreatic resection for PDAC from January 2010 to December 2016. The research found that the main prognostic factors for survival were age, sex, levels of carbohydrate antigen CA 19-9, tumor size, primary site, neo-adjuvant treatment (a treatment given to shrink a tumor before surgery), Charlson/Deyo score and facility type. For example, academic facilities were associated with better survival rates. The strength of the findings were validated by a high significant randomized test, log-rank test and simple hazard ratio.

One of the most critical findings is that the tumor engagement of peri-pancreatic arteries at pre-operative scans, historically considered by several centers a contraindication for surgery, does not have a negative impact on survival rates after resection.

"This is the only existing nomogram based on pre-operative objective variables able to assess the chance of long-term survival after surgery for PDAC," said Atsushi Oba, MD, PhD, research associate for surgical oncology, University of Colorado Department of Surgery, and lead author of the paper. "Our results suggest that current classifications of resectability on local anatomic and radiologic features should no longer be considered accurate and that more precise prognostic criteria should be defined. The new PDAC nomogram can become a useful tool for patients and counseling physicians in selecting therapy."

The study offers the advantage of estimating the outcome of each patient before an operation, and regardless of local anatomic features of the tumor, to understand if a patient qualifies or not for an operation based on his or her long-term predicted survival. The use of the nomogram in clinical practice should be proposed after a prospective validation.

"These results support the direction we're taking at the University of Colorado Anschutz Medical Campus," said Dr. Richard Schulick, MD, MBA, FACS, Chair of the Department of Surgery and Director of the University of Colorado Cancer Center on the campus. "By providing a multidisciplinary approach to the treatment of pancreatic diseases, we offer patients personalized care and can match candidates with different kinds of therapies that will work best for their individual case. The result is introducing a new concept of prognosis-based staging for patients and the possibility to overcome the old concept and limitations of the anatomical staging of the disease."

The behavior of one of nature's humblest creatures is helping astronomers probe the largest structures in the universe.

The single-cell organism, known as slime mold (Physarum polycephalum), builds complex filamentary networks in search of food, finding near-optimal pathways to connect different locations. In shaping the universe, gravity builds a vast cobweb structure of filaments tying galaxies and clusters of galaxies together along faint bridges hundreds of millions of light-years long. There is an uncanny resemblance between the two networks: one crafted by biological evolution, and the other by the primordial force of gravity.

The cosmic web is the large-scale backbone of the cosmos, consisting primarily of the mysterious substance known as dark matter and laced with gas, upon which galaxies are built. Dark matter cannot be seen, but it makes up the bulk of the universe's material. The existence of a web-like structure to the universe was first hinted at in the 1985 Redshift Survey conducted at the Harvard-Smithsonian Center for Astrophysics. Since those studies, the grand scale of this filamentary structure has grown in subsequent sky surveys. The filaments form the boundaries between large voids in the universe.

But astronomers have had a difficult time finding these elusive strands, because the gas is so dim it is hard to detect. Now a team of researchers has turned to slime mold to help them build a map of the filaments in the local universe (within 500 million light-years from Earth) and find the gas within them.

They designed a computer algorithm, inspired by slime-mold behavior, and tested it against a computer simulation of the growth of dark matter filaments in the universe. A computer algorithm is similar to a recipe that tells a computer precisely what steps to take to solve a problem.

The researchers then applied the slime mold algorithm to data containing the locations of 37,000 galaxies mapped by the Sloan Digital Sky Survey at distances corresponding to 300 million light-years. The algorithm produced a three-dimensional map of the underlying cosmic web structure.

They then analyzed the ultraviolet light from 350 quasars (at much farther distances of billions of light-years) cataloged in the Hubble Spectroscopic Legacy Archive, which holds the data from NASA's Hubble Space Telescope's spectrographs. These distant cosmic flashlights are the brilliant black-hole-powered cores of active galaxies, whose light shines across space and through the foreground cosmic web. Imprinted on that light was the telltale absorption signature of otherwise undetected hydrogen gas that the team analyzed at specific points along the filaments. These target locations are far from the galaxies, which allowed the research team to link the gas to the universe's large-scale structure.

"It's really fascinating that one of the simplest forms of life actually enables insight into the very largest-scale structures in the universe," said lead researcher Joseph Burchett of the University of California (UC), Santa Cruz. "By using the slime-mold simulation to find the location of the cosmic web filaments, including those far from galaxies, we could then use the Hubble Space Telescope's archival data to detect and determine the density of the cool gas on the very outskirts of those invisible filaments. Scientists have detected signatures of this gas for several decades, and we have proven the theoretical expectation that this gas comprises the cosmic web."

The survey further validates research that denser regions of intergalactic gas is organized into filaments that the team found stretches over 10 million light-years from galaxies. (That distance is more than 100 times the diameter of our Milky Way galaxy.)

The researchers turned to slime mold simulations when they were searching for a way to visualize the theorized connection between the cosmic web structure and the cool gas detected in previous Hubble spectroscopic studies.

Then team member Oskar Elek, a computational media scientist at UC Santa Cruz, discovered online the work of Sage Jenson, a Berlin-based media artist. Among Jenson's works were mesmerizing artistic visualizations showing the growth of a slime mold's tentacle-like network of food-seeking structures. Jenson's art was based on outside scientific research, which detailed an algorithm for simulating the growth of slime mold.

The research team noted a striking similarity between how the slime mold builds complex filaments to capture new food, and how gravity, in shaping the universe, constructs the cosmic web strands between galaxies and galaxy clusters.

Based on the simulation, Elek developed a three-dimensional computer model of the buildup of slime mold to estimate the location of the cosmic web's filamentary structure.

Although using a slime-mold-inspired simulation to pinpoint the universe's largest structures may sound bizarre at first, scientists have used computer models of these humble microorganisms, as well as grown them in petri dishes in a lab, to solve such complex problems as finding the most efficient traffic routes in large cities, solving mazes and pinpointing crowd evacuation routes. "These are hard problems to solve for a human, let alone a computer algorithm," Elek said.

"You can almost see, especially in the map of galaxies in the local universe from the Sloan data, where the filaments should be," Burchett explained. "The slime-mold model fits that intuition impressively. The structure that you know should be there is all of a sudden found by the computer algorithm. There was no other known method that was well suited to this problem for our research."

The researchers say that it is very difficult to design a reliable algorithm for finding the filaments in such a large survey of galaxies. "So it's quite amazing to see that the virtual slime mold gives you a very close approximation in just minutes," Elek explained. "You can literally watch it grow." Just for comparison, growing the organism in a petri dish takes days. Slime mold actually has a very special kind of intelligence for solving this one spatial task. After all, it's critical to its survival.

Enzymes are nature's powerhouses. Found in the cells of all animals, plants, and every other living organism, they accelerate the chemical reactions that trigger thousands of biological functions--from forming neurons to digesting food.

They perform their jobs so selectively and so quickly--millions of times faster than a blink of the eye--that the field of biomimetic chemistry has emerged over the past few decades with the goal of designing artificial enzymes that can mimic the powers of natural enzymes in industrial settings. Artificial enzymes could, for example, convert corn into ethanol or help create new drugs more quickly, cheaply, and effectively.

Moving one step closer to achieving that goal, Rajeev Prabhakar, a computational chemist at the University of Miami, and his collaborators at the University of Michigan have created a novel, synthetic, three-stranded molecule that functions just like a natural metalloenzyme, or an enzyme that contains metal ions.

"It wasn't clear that they could be made, but we made them. And, then we used them to successfully catalyze reactions," said Prabhakar, a professor of chemistry who studies enzyme reactions in hopes of designing their artificial analogues. "This is an incremental but important step in the development of artificial enzymes, which has long been considered chemistry's holy grail. Unfortunately, as good as natural enzymes work in our bodies and other life forms, they don't tolerate other settings very well. They're also very expensive and not easy to prepare and purify."

For their groundbreaking study published in Nature Chemistry this week, Prabhakar and graduate student Vindi M. Jayasinghe-Arachchige joined forces with Vincent L. Pecoraro, a University of Michigan chemistry professor, to improve the performance of the artificial enzymes Pecoraro's lab pioneered over the years. The Michigan researchers had previously created simpler synthetic metalloenzymes that successfully catalyzed a number of chemical reactions. But those artificial macromolecules were designed with three identical, or symmetrical "homotrimeric" strands, which, Prabhakar said, limited their catalytic abilities.

In the new molecule, which Jayasinghe-Arachchige designed on the University of Miami's supercomputer with Prabhakar's guidance, the third strand differs in structure from the other two strands. Her quantum mechanical calculations showed that the more complex, non-symmetrical, three-stranded structure, known as a "heterotrimeric" coil, expanded the catalytic performance of homotrimeric artificial metalloenzymes--a finding that Pecoraro and his team confirmed with experiments in his Michigan lab.

"Our techniques are different, but complimentary," Prabhakar said. "What we do the Pecoraro group cannot do, and what they do, we cannot do. We model molecules on the computer so we can predict their structural properties and the mechanism of their formations. They use our models to build the real thing, and in this case that is the first example of a natural heterotrimeric molecule."

Most lay people would probably find the study as incomprehensible as its title: "Heteromeric three-stranded coiled coils designed using a Pb(II)(Cys)3 template mediated strategy." But the bottom line, Prabhakar said, is that the collaborative research conducted in Miami and Michigan opens the door to a new strategy for achieving the creation of artificial enzymes that work as well as natural enzymes.

In addition to Pecocaro, Prabhakar, and Jayasinghe-Arachchige, other co-authors of the study include Prabhakar's former graduate student, Thomas J. Paul, now at the University of Michigan; Audrey E. Tolbert, Catherine S. Ervin, and Kosh P. Neupane, also from the University of Michigan; and Leela Ruckthong, from King Mongkut's University of Technology, in Thailand.

Now in her last year of study for her doctorate in chemistry, Jayasinghe-Arachchige said she remains fascinated by the advances in computational chemistry techniques that allowed her to model the chemical structures and reactions of the new molecule.

"I'm excited that our findings will create new avenues toward the development of efficient artificial enzymes that can be used to enhance the quality of life,'' said Jayasinghe-Arachchige, "and as a woman in a field where women are underrepresented, I hope this study will motivate women to join the fascinating world of STEM fields."