Culture

Genetic tools help identify a cellular culprit for type 1 diabetes

By mapping its genetic underpinnings, researchers at University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in type 1 diabetes, a condition that affects more than 1.6 million Americans.

The findings are published in the May 19, 2021 online issue of Nature.

Type 1 diabetes is a complex autoimmune disease characterized by the impairment and loss of insulin-producing pancreatic beta cells and subsequent hyperglycemia (high blood sugar), which is damaging to the body and can cause other serious health problems, such as heart disease and vision loss. Type 1 is less common than type 2 diabetes, but its prevalence is growing. The U.S. Centers for Disease Control and Prevention projects 5 million Americans will have type 1 diabetes by 2050. Currently, there is no cure, only disease management.

The mechanisms of type 1 diabetes, including how autoimmunity is triggered, are poorly understood. Because it has a strong genetic component, numerous genome-wide association studies (GWAS) have been conducted in recent years in which researchers compare whole genomes of persons with the same disease or condition, searching for differences in the genetic code that may be associated with that disease or condition.

In the case of type 1 diabetes, identified at-risk variants have largely been found in the non-coding regions of the genome. In the Nature study, senior author Kyle Gaulton, PhD, an assistant professor in the Department of Pediatrics at UC San Diego School of Medicine, and colleagues integrated GWAS data with epigenomic maps of cell types in peripheral blood and the pancreas. Epigenomic mapping details how and when genes are turned on and off in cells, thus determining the production of proteins vital to specific cellular functions.

Specifically, researchers performed the largest-to-date GWAS of type 1 diabetes, analyzing 520,580 genome samples to identify 69 novel association signals. They then mapped 448,142 cis-regulatory elements (non-coding DNA sequences in or near a gene) in pancreas and peripheral blood cell types.

"By combining these two methodologies, we were able to identify cell type-specific functions of disease variants and discover a predictive causal role for pancreatic exocrine cells in type 1 diabetes, which we were able to validate experimentally," said Gaulton.

Pancreatic exocrine cells produce enzymes secreted into the small intestine, where they help digest food.

Co-author Maike Sander, MD, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and director of the Pediatric Diabetes Research Center, said the findings represent a major leap in understanding the causes of type 1 diabetes. She described the work as "a landmark study."

"The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis."

Credit: 
University of California - San Diego

The way mice lick could reveal origins of neurological disorders

ITHACA, N.Y. - For the first time, Cornell University researchers have developed a technique for studying the neuroscience of motor control in mice ¬- by focusing on a mouse's tongue when it licks a water spout.

The technique incorporates high-speed cameras and machine learning in a tractable experimental setup that opens the door for revealing mysteries of how the motor cortex works, understanding the neural basis of related disorders like Parkinson's disease, and informing robots.

"We now have an approach in a mouse where we can bring all the tools of modern neuroscience to bear on this really classic problem of motor control," said senior author Jesse Goldberg, associate professor of neurobiology and behavior.

The field of motor control neuroscience has made advancements almost entirely through studies of monkeys reaching for things, Goldberg said. His lab tried for years to develop a mouse model for much faster and more malleable experiments but found too many constraints in getting mice to reach with their limbs; mice lack the necessary biomechanics and nature for such movements.

Tejapratap Bollu, a former graduate student in Goldberg's lab who was working on a different project that involved mice licking a water spout, made a discovery that led to the new technique. The water spouts were fitted with contact sensors, but often, the tongue would miss the target.

Bollu "noticed with his careful eye that [the mice] were actually sticking their tongues out and looking" for the spout, rather than licking as had been assumed, Goldberg said.

The movement in mice, which occurs on time scales of close to 100 milliseconds per lick, is analogous to a monkey reaching and making adjustments with its hand and activates the motor cortex in a surprisingly similar manner, the researchers found.

Using high-speed cameras, the researchers could observe the tongue reaching for the water spout, just as a human reaches for an object. They could also move the water spout, which forced a miss and an immediate correction. At the same time, genetically engineered mice allowed the researchers to use light to turn different parts of the brain on and off while the animals were drinking.

The researchers were able to use brain activation experiments to zoom in on the anterolateral motor cortex. "The electrical signals there exhibited remarkable similarity to the types of electrical signals people observed in primate reach tasks," Goldberg said.

"Now we can do experiments that have never been done before," he said.

Cornell Neurotech has developed technologies that make it possible to record thousands of neurons in an animal at once, for example. In next steps, Goldberg plans to use these tools to characterize for the first time the origins of pathogenic brain signals in neurological disorders, such as Parkinson's disease.

Credit: 
Cornell University

Study on bizarre rodent genetics solves a mystery and reveals another

Open up Scott Roy's Twitter bio and you'll see a simple but revealing sentence: "The more I learn the more I'm confused." Now the rest of the scientific world can share in his confusion. The San Francisco State University associate professor of Biology's most recent research, published earlier this month in one of the scientific world's most prestigious journals, catalogues a strange and confounding system of genes in a tiny rodent that scientists have ignored for decades.

"This is basically the weirdest sex chromosome system known to science," Roy said. "Nobody ordered this." But he's serving it anyway.

The owner of those chromosomes is the creeping vole, a burrowing rodent native to the Pacific Northwest. Scientists have known since the '60s that the species had some odd genes: Their number of X and Y chromosomes (bundles of DNA that play a large role in determining sex) is off from what's expected in male and female mammals.

That finding caught Roy's eye when presented by a guest speaker at a San Francisco State seminar, and he realized that modern technology might be able to shed new light on the mysteries hiding in the voles' DNA. After working with collaborators to disentangle the voles' genetic history -- resulting in one of the most completely sequenced mammal genomes that exists, according to Roy -- the story only got stranger.

The team found that the X and Y chromosomes had fused somewhere in the rodents' past, and that the X chromosome in males started looking and acting like a Y chromosome. The numbers of X chromosomes in male and female voles changed too, along with smaller pieces of DNA getting swapped between them. The researchers published their results in Science on May 7.

Drastic genetic changes like these are exceptionally rare: The way genes determine sex in mammals has stayed mostly the same for about 180 million years, Roy explains. "Mammals, with few exceptions, are kind of boring," he said. "Previously we would have thought something like this is impossible."

So how did the genes of this unassuming rodent end up so jumbled? It's not an easy question to answer, especially since evolution is bound to produce some strangeness simply by chance. Roy, however, is determined to figure out the "why." He suspects that what the team found in the vole's genome is something like the aftermath of an evolutionary battle for dominance between the X and Y chromosome.

The research couldn't have happened, Roy says, without collaborations with Oregon fish and wildlife biologists who had a creeping vole sample sitting in a lab freezer. He also teamed up with a group from Oklahoma State University when the two groups started chatting about creeping vole DNA sequences that were posted on the internet -- and both realized they were working on the same question.

Another key was working at a teaching-focused institution. Roy says he has the time to develop ideas with colleagues and students at SF State, and he can do research where he doesn't quite know what he'll find. "This is a great example of non-hypothesis-based biology," Roy explained. "The hypothesis was, 'This system is interesting. I bet if you looked into it some more, there'd be other interesting things.'"

It won't be the last time Roy's lab goes out on a limb. He and his collaborators plan to look into the genomes of other species related to the voles to chart the evolutionary path that led to this strange system. He'll also continue DNA sequencing curiosities across the tree of life.

"These bizarre systems give us a handhold to start to understand why the more common systems are the way they are and why our biology works as it does," he explained. By delving into the weirdest that nature has to offer, maybe we can come to understand ourselves better, too.

Credit: 
San Francisco State University

Nuclear terrorism could be intercepted by neutron-gamma detector that pinpoints source

image: Researchers, from left, Jana Petrovic, Bo Cederwall and Alf Göök test the new imaging technology on a mock-up of radioactive waste drum scanner.

Image: 
Biswarup Das

Scanning technology aimed at detecting small amounts of nuclear materials was unveiled by scientists in Sweden today, with the hope of preventing acts of nuclear terrorism.

Bo Cederwall, a professor of physics at KTH Royal Institute of Technology, says the technology can be used in airports and seaports for routine inspection of passengers and goods. The research is published and featured in the journals Science Advances and Science, respectively.

A form of tomography, the system enables quick 3D imaging of the source of neutron and gamma ray emissions from weapons-grade plutonium and other special nuclear materials, Cederwall says.

The so-called Neutron-Gamma Emission Tomography (NGET) system goes beyond the capabilities of existing radiation portal monitors, by measuring the time and energy correlations between particles emitted in nuclear fission, and using machine learning algorithms to visualize where they're coming from. The system looks for coincidences of neutron and gamma ray emissions--which when mapped together in real-time allow pinpointing their origin.

"The technology has a very high sensitivity and can within a few seconds detect gram-amounts of plutonium depending on the application and the plutonium isotope composition," Cederwall says. "It takes a little longer to get a really good picture so you can see exactly where the plutonium is. However, this can be done completely automatically."

But NGET isn't only for nuclear weapons and radiation-dispersing "dirty bombs"--it can be used to detect environmental radiation too, such as leaks from nuclear facilities or even natural sources. Cederwall says the research group is looking into equipping drones with the NGET system for this purpose.

"In case of a radiological emergency, It is extremely important to be able to quickly map the radioactive contamination in the environment in order to protect the population in the best possible way," he says.

Credit: 
KTH, Royal Institute of Technology

Study shows sharp decrease in Texas childhood vaccination rates during pandemic

image: Percent of children up-to-date with recommended childhood vaccine by age group - Texas, ImmTrac2, May 2010 to May 2020

Image: 
Texas A&M University

Despite expert recommendations that children continue to get regularly scheduled vaccines during the pandemic, vaccination rates have decreased in several states.

A new study by researchers from the Texas A&M University School of Public Health and several other research institutions looked at childhood immunization rates in Texas to see what effect the COVID-19 pandemic may have had on childhood immunizations in 2020. In the study, led by public health doctoral student Tasmiah Nuzhath and published in the journal Vaccine, the researchers used data from a statewide immunization registry to determine how immunization rates changed over a 10-year period for children at four age milestones: one month, five months, 16 months and 24 months. The researchers also analyzed county-level data from 2019 and 2020 to compare rural and urban locations.

To see how much effect the pandemic had on vaccination rates in Texas, the research team analyzed data from the ImmTrac2 immunization registry from May 2010 through May 2020. The data was provided by the staff at Texas Department of State Health Services (DSHS) and included immunization records for more than 300,000 Texas children from birth to 24 months. Their analysis found that the proportion of children who were current on recommended vaccines in the four age categories increased between 2010 and 2019. However, there were sharp decreases in vaccination between 2019 and 2020 in most categories, which the authors attributed to the COVID-19 pandemic.

The decline in vaccinations the researchers found was similar to those found in other states. The declines were greatest for the 5-month-old and 16-month-old groups. The age groups saw 47 percent and 58 percent declines, respectively.

Their analysis of county-level data found that 5-month-old children in rural locations had greater declines in immunization rates than those living in urban areas. They also found that there was no decrease in Hepatitis B vaccines at birth. This points to immunizations that take place in clinics or doctor's offices as opposed to hospitals being the most affected by the pandemic.

Researchers also found that uptake of most vaccines appeared to increase prior to the pandemic between May 2010 and May 2019, with the exception of measles vaccine. MMR (measles, mumps and rubella) coverage has been declining in Texas since 2015, and is currently below the 95 percent coverage level required to achieve herd immunity. The already low level of measles vaccination coverage, exacerbated by the pandemic, increases the risk of a measles outbreak in Texas and could have substantial public health consequences.

The findings of this study are in line with those focusing on other states, but the researchers note that the findings are limited by their data source. ImmTrac2 is an opt-in registry, which means that the data may not reflect the population as a whole. However, despite this limitation, the findings point to possible disruptions in vaccination services as well as disparities between rural and urban communities. These results indicate that there is a need for better targeted public health communication to address perceived risks and for improved vaccination infrastructure to help overcome barriers to vaccination in rural areas.

Credit: 
Texas A&M University

New pan-European research reveals double the concern about mental health impact of Lockdown and associated restrictions than physical inactivity

Nearly two thirds (61%) expressed concern about their worsening mood in Lockdown and associated restrictions1.

34% said they felt more anxious and 28% felt more depressed during Lockdown and associated restrictions1.

Coffee helped lift nearly half (44%) of adult's negative moods in Lockdown and associated restrictions1.

A new pan-European survey funded by the Institute for Scientific Information on Coffee exploring the impact of COVID-19 Lockdowns and associated restrictions (in those countries where there has been no Lockdown), has found that nearly two thirds of adults (61%) expressed concern about their worsening mood; two times higher than those concerned about physical inactivity (24%)1.

Understanding the effects of COVID-19 restrictions on physical and mental health

The new survey of 5,170 adults aged over 18, across the UK, Italy, Finland, Germany and Poland, sought to better understand people's perceptions of the effect of COVID-19 restrictions on their physical and mental health, and aspects they felt most impacted their mood. It also sought to explore the role that everyday pleasures such as coffee had, and other simple ways that people found to lift their mood during Lockdowns and associated restrictions1.

In terms of the impact on mental health, 34% admitted to having felt more anxious, and 28% having felt more depressed1. These findings mirror other recent research on the impact of Lockdown and associated restrictions on mental wellbeing, which shows a three-fold increase to the prevalence of anxiety in the general population2 and a seven-fold increase in the prevalence of depression3 globally.

Of those in the survey who identified exercise as playing an important part in their daily routines, nearly a quarter (24%) said that not exercising negatively impacted their mood, while 27% said they used exercise as a means to lift their mood1.

Supporting people to make positive and healthy choices

The research revealed ways people had found helped improve their mood, with nearly half (44%) saying that taking time to enjoy a few cups of coffee a day helped, as did getting more sleep (31%), and eating and drinking more healthily (30%)1.

The finding that coffee had a beneficial effect on people's mood reflects previous research, which demonstrates that coffee helps to improve mood when consumed throughout the day 4, as well as enhancing alertness and attention (concentration) 5.

Nearly a third (28%) of respondents said that coffee helped motivate them to exercise and that it helped enhance their physical performance1. These findings are supported by previous research, which demonstrates that caffeine in coffee helps to improve physical performance during exercise6, 7.

Assistant Professor Giuseppe Grosso, Department of Biomedical and Biotechnological Sciences School of Medicine, University of Catania, commented: "These findings highlight the considerable, and wide reaching impact of Lockdown and associated restrictions. While this is concerning, it is helpful to see that many have found small ways to break up their routines and improve their moods during Lockdown and associated restrictions, through interventions as simple as making time to exercise or enjoying a coffee break."

"With regards to coffee breaks, this beneficial effect is likely two-fold. Firstly through the holistic benefit of taking time to relax and enjoy coffee's flavour and aroma. Additionally, coffee consumption has been demonstrated to improve mood, alertness and reduce feeling of fatigue through the acute effect of caffeine and the potential role of coffee polyphenols in neurogenesis and long-term maintenance of a healthy brain (and consequent reduction in some affective and neurodegenerative disorders)."

Geographic and gender differences

The survey revealed how impacts on mood and depression were most prominent among females, in younger age groups (aged 34 and under), and in parents with dependent children under the age of 18; which may be a result of women bearing a larger share of the home/childcare burden1. Differences were also seen between countries, with Italy and Poland reporting the highest levels of impacted mood, and feelings of anxiety and depression1 which is likely to be, for Italy in particular, reflective of the scale of the COVID-19 crisis.

In fact out of all countries surveyed, when it came to the impact of Lockdown and associated restrictions on dips in mood, this was most keenly felt in Poland where three quarters (75%) of people admitted it had declined, closely followed by Italy (72%), compared to under half in Finland (45%), 50% in the UK and 63% in Germany. Yet, when it came to the role coffee had in improving spirits, around half of people in Italy (53%) and Poland (47%) agreed that drinking a few cups of coffee a day helped to lift their mood, followed by Finland (43%), the UK (37%), and Germany (36%).

The growing appreciation for coffee as part of mood-boosting routines

As many reported a benefit to mood through drinking coffee, it was also found that nearly half of coffee drinkers (42%) increased their intake in Lockdown and associated restrictions. This was particularly the case in Italy with over half (52%) increasing their daily intake, compared to Finland (33%), Germany (39%), Poland (44%) and the UK (38%)1.

Shedding light on the ways that people enjoyed coffee during Lockdown and associated restrictions, it was found that a third (32%) of coffee drinkers said they tended to drink coffee at regular intervals to break up the day at home, whereas 43% said they relied on coffee to start the day and 30% drank coffee at times where they could relax. In fact, 35% of coffee drinkers said they appreciated their coffee breaks more during Lockdown and associated restrictions1.

While the mental wellbeing impact of Lockdown and associated restrictions is far reaching, the survey results highlight that adapting and finding small ways to help lift mood can be beneficial; whether through adopting healthy eating, taking time to enjoy a coffee or making time for exercise1.

Credit: 
Kaizo

New report indicates annual economic impact of human genetics/genomics

WASHINGTON, DC (May 19, 2021) - Human genetics and genomics contributed $265 billion to the U.S. economy in 2019 and has the potential to drive significant further growth given major new areas of application, according to a new report issued today by the American Society of Human Genetics (ASHG). The findings indicate that this research and industry sector has seen its annual impact on the U.S. economy grow five-fold in the last decade and outlined at least eight areas of expanding impact for human health and society. ASHG commissioned and funded the report and is grateful for generous additional contributions from Invitae and Regeneron. Neither company had any direct input into the analyses or report content.

"Twenty years after the Human Genome Project produced the first draft of the human genome sequence, we are seeing in more and more areas the very profound benefits of genetics and genomics to human health," said ASHG President Gail Jarvik, MD, PhD. "This report also reveals the significant benefit to the American economy and outlines future areas of functional application and impact for the field."

The report finds that human genetics and genomics research in 2019 yielded a substantial $4.75 return on every federal dollar invested in it. This determination reflects, in part, an estimated $3.3 billion in 2019 federal funding specifically for human genetics and genomics research, largely at the National Institutes of Health (NIH), in comparison to the $15.5 billion that the field generated and supported in federal tax revenues that year.

"While the report uses a conservative $3.3 billion figure, we were surprised to learn in this analysis that nearly half of all NIH funding has a genetic/genomic component, if not as the focus, then as a tool to support other biomedical research," said Lynn B. Jorde, PhD, Chair of ASHG's Government and Public Advocacy Committee. "It demonstrates how foundational genetics is for biomedical research today."

The impact on job creation is equally robust. Human genetics and genomics research enabled and supported a total of 850,000 jobs in 2019, including direct and indirect employment. This number included 152,000 industry jobs across core private-sector genetics/genomics companies (more than 89,000 jobs) and in extended industries such as major pharmaceutical and medical testing/diagnostics companies where human genetics plays an increasingly important role (nearly 63,000 jobs).

According to Jarvik, all medical science produces great returns to individuals and to society, and human genetics and genomics research is an enormous contributor in both respects. "This field is perhaps one of the best examples of the value of scientific research to our entire economy and of the case for continuing to build on that investment," she said.

To illustrate the scope of current uses of genetics or genomics, the report highlights eight major categories for emerging or future medical application: minable big data, identification of genetic predisposition to diseases and disorders, diagnosis of diseases, rational drug development that relies on genetic information to target molecules in drug design, pharmacogenomics (or personalized medicine), gene editing and gene therapy, human-microbe genetic interactions, and human-environment metagenome interactions. In addition, it describes non-medical applications as diverse as forensic science, anthropology and evolutionary biology, ancestry testing, and paternity testing.

"The report relied on 2019 data, but 2020 showed us the enormous value of genomic sequencing for viruses alone, with the creation of mRNA-based COVID-19 vaccines in an unprecedented timeframe," said Simon Tripp, a Principal and Senior Director at TEConomy Partners, and co-author of the report. "In another example, we can see that genomics-based precision medicine is not only growing in applications for cancer treatment, it is also advancing applications in the treatment of heart disease, rheumatoid arthritis, Alzheimer disease, multiple sclerosis, and many other conditions." Tripp also notes that the field of genetics and genomics is absolutely essential in developing diagnostics and treatments for thousands of rare diseases, which collectively affect more than 25 million people in the U.S. and 250 million worldwide.

Methodology:

To assess the field's total economic impact, the report's authors considered direct, indirect, and induced effects. Direct effects included human genetics and genomics research expenditures, services and corporate operations in the U.S. Indirect effects were defined as purchase of secondary inputs and services from U.S. suppliers and manufacturers. Induced effects were comprised of disposable income spending in the U.S. economy by those employed in human genetics and genomics research and related industries. All estimates in the report represent the most conservative numbers identified in the process of the authors' analysis. The estimation of economic impact is based on an input-output (I-O) model. For modeling and estimating expenditure impacts, TEConomy used a 2019 IMPLAN I-O economic impact model of the U.S. IMPLAN is the nation's most widely used economic impact modeling data and analysis platform.

Credit: 
American Society of Human Genetics

Study raises new alarm over long-term exposure to second-hand smoke

Chronic exposure to second-hand smoke results in lower body weight and cognitive impairments that more profoundly affects males, according to new research in mice led by Oregon Health & Science University.

The study published today in the journal Environmental Health Perspectives.

"The hope is that we can better understand these effects for policymakers and the next generation of smokers," said lead author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. "Many people still smoke, and these findings suggest that that the long-term health effects can be quite serious for people who are chronically exposed to second-hand smoke."

The research examined daily exposure of 62 mice over a period of 10 months. Researchers used a specially designed "smoking robot" that went through a pack of cigarettes a day in ventilated laboratory space at OHSU. The longest previous study of this kind lasted three months.

"Nobody has done this, ever. This study is unique," Raber said. "It really gives you the ability to look at long-term effects."

"This study more accurately replicates the human experience by daily exposing mice to cigarette smoke," added senior author Glen Kisby, Ph.D., professor of pharmacology at Western University of Health Sciences in Lebanon, Oregon.

Second-hand smoke is already considered a risk factor for dementia in people, but the new study put the theory to the test.

Researchers first divided mice into two groups - one wild-type and one expressing the human tau protein, important in Alzheimer's-like dementia. Starting in April of 2018, they exposed mice to cigarette smoke for 168 minutes a day, then conducted behavioral and cognitive testing. They also examined lung and brain tissue.

Key findings:

Smoke harms 'healthy' mice. Researchers theorized that second-hand smoke would be especially harmful for mice with the human tau protein. However, "we actually found the opposite," Raber said. In many of the behavioral and cognitive tests - including swimming speeds and migrating through a maze - wild-type mice were more affected than human tau mice after both groups were exposed to second-hand smoke.

Smoke especially harms males. Researchers discerned a clear sex-related difference in cognition, with clearly discernable changes in the hippocampus region of the brain among males compared to females.

Loss in body weight. Researchers found lower body weights in wild-type mice following second-hand smoke compared with human tau mice. Further, they also noticed that males were disproportionately impacted by a loss in body weight compared to females.

Brain changes: Researchers discovered more profound changes in metabolic pathways, which are linked chemical reactions, in the brains of wild-type males than females. Researchers also found more profound effects in the brains of wild-type than the human tau mice.

Although smoking rates have declined in recent generations in some countries, smoking - and exposure to second-hand smoke - remains widespread in much of the world. The World Health Organization estimates 1.5 to 1.9 billion people worldwide will be smokers in 2025.

"Long-term exposure to second-hand smoke triggers detrimental changes," Raber said. "Based on our study, it seems that males might be more susceptible than females. People should take that into consideration."

Credit: 
Oregon Health & Science University

New, biological, and safer soaps

image: INRS Professor Charles Gauthier, specialist in chemistry of carbohydrates and natural products, who led the research.

Image: 
Christian Fleury

An international research team led by Professor Charles Gauthier from the Institut national de la recherche scientifique (INRS) has discovered a new molecule with potential to revolutionize the biosurfactant market. The team's findings have been published in Chemical Science, the Royal Society of Chemistry's flagship journal.

Surfactants are synthesized from petroleum and are the main active ingredient in most soaps, detergents, and shampoos. Biosurfactants, produced by bacteria, are safer and can replace synthetic surfactants.

Rhamnolipid molecules are some of the safest surfactants known and are particularly attractive, thanks to their biodegradability, minimal toxicity, and amenability to be produced from industrial waste. But there's a problem. They are made using Pseudomonas aeruginosa, a pathogenic bacterium harmful to humans.

"If we want to fully gain the benefits of rhamnolipids, we need to grow these pathogenic bacteria on a huge scale. And because that's a health risk, the industry is looking for alternatives," explained Professor Gauthier. The molecules produced by these bacteria are usually mixed with other compounds or virulence factors, making them trickier to use.

To address the problem, the research team identified molecules that resemble rhamnolipids in Pantoea ananatis, a non-pathogenic bacterium. The team was then able to chemically synthesize these molecules, called ananatosides, in the laboratory, raising the possibility that they could be produced on a larger scale than using bacteria. The industry is already showing interest in these promising new biosurfactants.

A look at the structure

The new molecule comes in two different forms, A and B. Ananatoside A structure is described as closed, while B is open. The molecule A is closed in on itself to form a loop. The process that closes the loop is called lactonization, and it has also been achieved with rhamnolipids to create new molecules.

The team has shown that the lactonized form has a large impact on the biological action of the molecules. It minimizes the surface-active properties of rhamnolipids and renders them toxic.

Now the researchers want to characterize further new biosurfactants and make the molecules more stable.

An interdisciplinary team

INRS professor Éric Déziel helped with the research as an expert on biosurfactants. His team produced and isolated ananatosides produced naturally from the bacteria Pantoea.

Mayri Alejandra Dìaz De Rienzo, a lecturer at the Liverpool John Moores University in England, also took part as an INRS guest professor. Her expertise in the fermentation and downstream processing of biosurfactants helped the team identify the surface-active properties of these new biosurfactants.

Maude Cloutier, a PhD student and recipient of a Vanier Canada Graduate Scholarship, and Marie-Joëlle Prévost, a recipient of a summer scholarship from the Natural Sciences and Engineering Research Council of Canada (NSERC), aided the team with their chemical synthesis work in the laboratory.

Credit: 
Institut national de la recherche scientifique - INRS

Same nerve cell -- Different influence on food intake

image: 3D rendering of POMC neurons in the hypothalamus.

Image: 
MPI for Metabolism Research/ Nasim Biglari

The nerve cells, also called neurons, in our brain control all the basic processes of our body. For this reason, there are different types of neurons distributed over specific regions of the brain. Researchers at the Max Planck Institute for Metabolic Research and the CECAD Cluster of Excellence in Aging Research of the University of Cologne have developed an approach that allows them to show that neurons that are supposedly the same are actually very different: they not only sense different hormones for the body's energy state, but also have a different influence on food intake. This can have a direct effect on our metabolism, for example by differentially restraining our appetite.

The brain processes our sensory perceptions, controls our behaviour and stores our memories. Because of these many functions, different types of nerve cells with specific tasks exist in different regions of our brain. One such type of nerve cells are the so-called POMC neurons, which play an important role in the metabolism of our body. "POMC neurons are critically involved in the control of appetite, energy expenditure and metabolism," explains Nasim Biglari, a recently graduated PhD and first author of the study. "In recent years, it has been increasingly confirmed that POMC neurons are more diverse than previously thought." Such differences result, for example, from a different response to hormones secreted by the body and are only noticeable when individual POMC neurons are compared with each other. In such a case, scientists refer to different subtypes of neurons. "Whether the different subtypes also play a different role in metabolism has not been clarified so far," says Nasim Biglari.

Same nerve cell - different influence on food intake

"We have now succeeded in making different subtypes of neurons visible in mice at the genetic level and thus were able to subject them to more detailed investigation", says Nasim Biglari. "Using this new, genetic approach, we were able to describe two different subtypes of POMC neurons in detail for the first time. For example, our results show a different distribution of the two subtypes within the same specific brain region. Moreover, they sense different hormones for the body's energy state. The two subtypes even act differently on food intake, with one part of the POMC neurons suppressing appetite more potently than the other." Because of the influence of POMC neurons on metabolism and food intake, these observations could also be relevant to diseases such as obesity and diabetes.

"We were able to show for the first time that the diversity of POMC neurons is important for their function in the control of metabolism. In further experiments, we would like to increasingly address the questions of how the two subtypes of POMC neurons influence metabolism in detail and which neuronal circuits in the brain they engage to carry out their effects", Nasim Biglari is looking forward to future experiments. "More generally, however, the approach we have developed can also be used to identify cell subtypes in other organs and for other types of cells. This could lead to many more insights into the diversity of our body's cells."

Credit: 
Max-Planck-Gesellschaft

Plant consumers play unexpectedly large role in the evolution of seedling success

image: At UC San Diego's Biology Field Station, scientists tested California grasses in plots that allowed or excluded the influence of birds, mice, rabbits and other plant consumers.

Image: 
Cleland Lab, UC San Diego

For young plants, timing is just about everything. Now, scientists have found that herbivores, animals that consume plants, have a lot to say about evolution at this vulnerable life stage.

Once a plant seedling breaches the soil surface and begins to grow, a broad range of factors will determine whether it thrives or perishes.

Scientists have long perceived that natural selection favors early rising seeds. Seedlings that emerge early in the growing season should have a competitive advantage in monopolizing precious soil resources. Early growth also should mean more access to light, since early growers can block sunlight for seedlings that emerge later in the season.

Despite plenty of proof that germinating early is highly advantageous, many plants germinate later. Why?

University of California San Diego researchers found in a recent study that herbivores have a lot to say in determining how germination time contributes to plant growth.

Research published in the journal Evolution Letters by former UC San Diego graduate student Joseph Waterton and Division of Biological Sciences Professor Elsa Cleland has shown that certain vertebrate herbivores--including mice, rabbits and birds--play an underappreciated role in shaping natural selection in plant growth. Due to earlier seasonal growth patterns emerging from climate change, the new findings may factor into evolutionary responses to global environmental changes.

"Germination timing is a really important trait that influences the fitness of plants and their ability to survive and reproduce," said Waterton, who received his PhD in Biological Sciences and is now at Indiana University. "Until this study we didn't understand the role herbivores played in the evolution of this trait--we had very little idea of what shaped this trait besides aspects of the abiotic environment, such as climate."

In field studies using two California grass species, Waterton and Cleland found that early emerging seedlings were more impacted by vertebrate herbivores compared to those that emerged later, likely because they were the first and biggest bits of greenery available on the landscape at the start of the growing season when not much else was growing. They found that such early season consumption by herbivores shrinks the benefit of early seedling emergence.

Conducted at the UC San Diego Biology Field Station in early 2018, the researchers' study examined native Stipa pulchra and non?native Bromus diandrus grasses, common California grass species with vastly different origins and growth strategies, in neighboring plots that either excluded or allowed access to vertebrate herbivores. Herbivores consistently weakened the success of early emergers in both grass species, the results showed.

With climate change forces shifting the timing of many plant life stages earlier in the year, the new study shows that herbivores are likely working as a counteracting force.

"Plants that germinate earlier than their neighbors tend to win out. But our study shows that herbivory early in the growing season can counteract the advantage of early germination," said Cleland, a professor in the Ecology, Behavior and Evolution Section. "This is important because in order to persist and keep pace with climate change, many species will need to shift their seasonal timing. Our study shows that we can't accurately estimate the strength of natural selection on key traits if we don't account for realistic forces acting in nature, such as herbivory on plants."

Credit: 
University of California - San Diego

TTUHSC study: Virus, restrictions increase mental health risks for nursing home caregivers

image: Ashish Sarangi, M.D., from the Texas Tech University Health Sciences Center recently conducted research into the mental health consequences of COVID-19 geriatric care in a nursing home setting.

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TTUHSC

No matter one's age, race, gender, socioeconomic status or political party, COVID-19 has impacted everyone at some level. That impact has been especially palpable for the approximately 1.3 million elderly Americans who reside in the country's 15,600 nursing homes.

Inside these facilities, the forced isolation caused by COVID-19 disrupted daily routines and left many of the residents with higher-then-normal levels of stress, anxiety and depression. Because many of these elderly individuals lack the resources or knowledge to use communications tools such as FaceTime or Zoom, their family and friends had no way to visit them except through a facility window.

What these family members couldn't see as they peered through their loved one's glass frame was the mental toll the pandemic was taking on the facility's health care staff.

To better understand this toll, Ashish Sarangi, M.D., recently conducted research into the mental health consequences of COVID-19 geriatric care in a nursing home setting. His research, "A Descriptive Study Evaluating the Impact of COVID-19 on Delivery of Care and Mental Health of Geriatric Nursing Home Staff," was published in the April issue of the American Journal of Geriatric Psychiatry. The study also was presented in March during the honors alumni session at the American Association of Geriatric Psychiatry's annual meeting.

Sarangi, co-chief psychiatry resident at the Texas Tech University Health Sciences Center (TTUHSC) School of Medicine, conducted his research at a nursing home facility in Lubbock, Texas using an online survey that was distributed to staff physicians, registered nurses and LVNs.

"What we found is that there was a lot of mental health impact on the staff members, and the reasons were anywhere from working through optimally long hours to they didn't have enough PPE (personal protective equipment) available," Sarangi said. "They're fearful of contracting COVID and taking it home to their families and there was just, overall, a lot of stress and negative mood as well."

Many of the facility's staff members did indeed contract COVID-19, requiring them to quarantine at home while others worked extended shifts to cover the time missed. The stress of working longer shifts was compounded by the lack of PPE.

"That was very challenging for them," Sarangi said. "Also, there were no visitors allowed either for the patients or staff members. It was pretty much a lockdown facility for 10 to 12 hours a day and they didn't have any kind of mental support; there was no counseling or anything like that going on."

The facility employed telemedicine and other electronic platforms to help offset staff concerns about contracting the virus and ease the sense of isolation among staff and residents. However, Sarangi said, many residents and staff found the use of technology unhelpful. Most residents simply weren't able to successfully navigate the platforms and staff found that it added to their sanitation burden. The more equipment the technology required, the more time they had to spend sanitizing it before its next use.

In addition, the same stress that was causing mental health issues for staff and residents also was affecting their physical health. Sarangi said this is important because stress, no matter its source, can predispose people to cardiovascular conditions such as heart attacks and strokes.

"Even if you're perfectly healthy or don't have any pre-existing conditions, stress can also lead to diabetes and actually increase your risk for infections like COVID-19," Sarangi added. "And if you are chronically stressed, it can affect your immune system and predispose you to COVID-19 as well."

The availability of vaccines have eased some of the stress related to COVID-19, but Sarangi said staff still work under a cloud of fear that will likely remain until the pandemic ends. They worry every day about whether they've contracted the disease, or worse, passed it on to a family member at home or to an elderly nursing home resident.

"It's like walking into a fire sometimes because some of these long-term care facilities, at least in the heat of the pandemic, they were pretty much hotspots for COVID-19," Sarangi emphasized. "It's something that we don't really think about in Lubbock, but it also happens here a lot. We still have a lot of nursing homes and long-term care facilities here and I think they need the mental health support; they need resources. I think that would be the main take-home point of this study."

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Texas Tech University Health Sciences Center

Workplace pandemic protocols impact employee behavior outside work

VANCOUVER, Wash. - Employer COVID-19 safety measures influenced worker precautions even when they were not on the clock, according to a new study out of Washington State University.

The study found that workplace cultures that adopted COVID-19 prevention measures, such as daily health checks and encouraging sick workers to stay home, resulted in less "sickness presenteeism" or going places when feeling ill. The effect was found both inside and outside of work - meaning fewer employees with COVID-19 symptoms showed up to work and other public places like grocery stores, gyms and restaurants.

The same held true for attitudes toward the COVID-19 prevention measures recommended by the Centers for Disease Control and Prevention such as mask wearing and social distancing: employees working for companies with strong COVID-19 prevention measures were more likely to have positive attitudes toward the CDC guidelines.

"The workplace COVID-19 climate had a direct effect on shaping employee attitudes towards the personal, preventative health actions that the CDC recommends," said Tahira Probst, WSU psychology professor and lead author of the study published in the Journal of Occupational and Environmental Medicine. "Public health officials and employers should be aware of the impact that organizations and workplaces can have on stemming the tide of the pandemic. It's not just that employers have an impact on transmission that occurs within the workplace, but they are also influencing those same employees' attitudes and behaviors outside of the workplace."

For the study, the researchers surveyed more than 300 working adults recruited on the Amazon Mechanical Turk crowdsourcing website in three waves during the pandemic holiday surge. They first surveyed the workers in October 2020 to assess the COVID-19 climate of their workplaces; then in December 2020, about their attitudes toward the CDC prevention guidelines, and finally in February 2021, about their work and non-work behaviors when sick or exposed to COVID-19.

The study found a significant connection between the workplace COVID-19 climate, employee attitudes toward the pandemic prevention measures, and ultimately whether they showed up to work or other public places while feeling ill with COVID-19 symptoms or following known exposure to the virus.

The respondents came from 44 U.S. states and Washington D.C. While the survey did not use a nationally representative sample, the respondents' demographics--with a median age of 40, 59% male and 76% white--aligned well with the general labor force with a median age of 40-44, 53% male and 78% white. However, the survey group was generally more highly educated with 67% reporting having a college degree or higher, compared to 40% in the general labor force.

During the survey period, about half of the respondents were working onsite and half remotely. Interestingly, the study found that even the remote workers were influenced by their employers' COVID-19 workplace climate. Remote workers were less likely to frequent public spaces after exposure to the virus or while ill when working for a company with strong prevention measures in place.

The researchers noted that the many U.S. organizations have long-standing cultures stigmatizing sick leave and encouraging sickness presenteeism. The good news, the authors point out, is that workplaces can help curb the spread of COVID-19 by actively encouraging sick employees to stay home, instituting daily health checks, and adopting other CDC workplace health and safety precautions.

The pandemic has forced some organizations to examine their culture around sick leave, and Probst is interested to see if this will become a long-term change.

"One of the more enduring consequences of the pandemic might be that organizations not only offer more sick leave but also encourage employees to stay home if they're sick," said Probst. "Frankly, prior to COVID-19, a lot of our culture has been: 'unless you're gravely ill and can't get out of bed, you should be at work.' That behavior spreads diseases and ultimately reduces productivity. We're hopeful that the pandemic might institute a re-thinking of this norm moving forward."

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Washington State University

Case Western Reserve researchers identify potential approach to controlling epileptic seizures

image: Lin Mei

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Case Western Reserve University

Researchers from Case Western Reserve University have identified a potential new approach to better controlling epileptic seizures.

Lin Mei, professor and chair of the Department of Neurosciences at the Case Western Reserve School of Medicine, who led the new study in mouse models, said the team found a new chemical reaction that could help control epileptic seizures.

Their findings were recently published in The Journal of Clinical Investigation.

Epilepsy is a neurological disorder in which abnormal brain activity causes seizures or periods of unusual behavior, sensations and sometimes loss of awareness.

A human brain contains about 86 billion nerve cells, also known as neurons. Eighty percent of them--known as excitatory neurons--send messages to bundles of nerves that control muscles, typically calling on them to do something. In a healthy brain, activity that excitatory neurons inspire is managed by the remaining 20% of nerve cells, called inhibitory neurons.

"This balance between excitatory and inhibitory neurons is absolutely important for everything that we do,'' Mei said. "When the balance is tilted, so that excitatory neurons are super active, there will be a problem. It's highly likely there will be epilepsy.''

Two mechanisms cause epilepsy: One is genetic; the other is environmental.

In Dravet syndrome, a genetic type of epilepsy that is among the more severe forms of the condition, the sodium channel--a membrane pore critical for inhibiting neuron activation--is mutated and allows excitatory neurons to misfire, causing seizures.

"It would be great if you could find a mechanism to make the sodium channels more stable,'' Mei said.

He and his colleagues found that a chemical reaction in the brain, called neddylation, stabilizes the sodium channel in mouse models. When the researchers produced a mouse that lacked the protein required for neddylation in inhibitory neurons, it developed epilepsy. The surprising emergence of the condition inspired the team to explore the neddylation process in more depth; eventually they discovered that neddylation plays a critical role of for the sodium channel.

"If we have that chemical reaction in check," he said, "you could help control epilepsy.''

Mei said the research provided evidence that a mutation in patients with epilepsy had a problem with neddylation, suggesting "neddylation theory" may apply to human patients.

The next step in their research, he said, is to identify drugs or approaches that can manipulate this chemical reaction to stabilize the sodium channel. The researchers are also conducting further experiments to determine whether this applies to patients with other types of epilepsy, not just Dravet patients.

"Our finding that neddylation can prevent epilepsy in mouse models represents a new direction for future research," he said. "With this new lead, scientists or pharmaceutical companies can look for chemicals to boost neddylation. The concept is still in an early stage and much needs to be done to make a difference for patients."

This chemical reaction--neddylation--has also been considered a target for cancer research, Mei said, so it could have applications beyond epilepsy.

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Case Western Reserve University

'We're playing Moneyball with building assets'

Researchers have developed a tool to help governments and other organizations with limited budgets spend money on building repairs more wisely.

The new tool uses artificial intelligence (AI) and text mining techniques to analyze written inspection reports and determine which work is most urgently needed.

"Those assessments are now largely subjective, the opinions of people based on experience and training," said Kareem Mostafa, an engineering PhD student at the University of Waterloo who led the project. "We're using actual data on buildings to make spending decisions more objective."

Researchers looked at inspection reports on the roofs of 400 schools managed by the Toronto District School Board. A computer model was developed to search the one- to two-page reports for about 30 keywords, including words such as 'damage' and 'leaks.'

By analyzing the frequency of the keywords, plus factors including the age of roofs, the AI software divided the schools into four categories based on the urgency of repair or replacement. The goal was to give the school board an objective way to target its limited funds, speeding up the assessment process and helping it spend money where it makes the most sense.

"We're playing Moneyball with building assets," Mostafa said. "By using data on buildings instead of opinions, our model also takes potential political headaches out of the process."

Although the software was developed to assess the need for roof repairs, it can be tweaked to help prioritize other kinds of work for organizations with budget limitations and many buildings to maintain.

Mostafa is also working to incorporate other kinds of data, including AI analysis of photographs, into the assessment model.

Tarek Hegazy, a professor of civil and environmental engineering at Waterloo, and Ahmed Attalla, a project manager with the school board, collaborated on the study.

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University of Waterloo