Research Roundup: How Viruses Replicate, Food Additives, Stroke and More

There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.

How Deadly Viruses Replicate

Researchers with Harvard Medical School identified a key mechanism that allows some of the deadliest human RNA viruses to replicate specific pieces of their viral genome. Some RNA viruses inject their entire viral genome into a cell in a single piece, while others cut it up into pieces. The latter are named segmented viruses. The researchers found that in segmented viruses, the mechanism is activated by an RNA from the opposite end from where the segment copying starts. They published their research in the journal PNAS.

“Climate change has altered and intensified the spread of some serious and emerging viruses to new geographic regions, creating an acute challenge to global health,” stated Sean P.J. Whelan, professor of microbiology at Harvard Medical School and director of the Harvard Program in Virology. “Our findings identify a critical mechanism that allows some of these pathogens to replicate and survive.”

For example: Lassa fever infections, which have a mortality rate of 50% during epidemics. Whelan and his co-author Jesse Pyle studied the Machupo virus, an arenavirus, which infects rodents (like Lassa viruses) that then transmit the virus to humans, resulting in fatal hemorrhagic fevers. Machupo virus has two segments, compared to the flu virus, which has eight. Now they understand the mechanism of how the virus inserts its segments, which may provide new approaches to therapies for segmented viruses.

Common Food Additive Affects Gut Microbiota

Researchers with the University of Sydney in Australia found that a common food additive, E171 (titanium dioxide nanoparticles), which is also found in some medicines as a whitening agent, affects the microbiota, the trillions of bacteria and fungi that live in the human body. E171 is found in more than 900 food products, including chewing gum and mayonnaise. Its impact on the gut microbiota seems to contribute to inflammation in the colon. They published their research in Frontiers in Nutrition.

“It is well established that dietary composition has an impact on physiology and health, yet the role of food additives is poorly understood,” stated Wojciech Chrzanowski, co-lead author of the study. “There is increasing evidence that continuous exposure to nanoparticles has an impact on gut microbiota composition, and since gut microbiota is a gate keeper of our health, any changes to its function have an influence on overall health.”

The research was conducted on the effects of titanium dioxide on gut health in mice. The chemical did not change the composition of gut microbiota, but it did affect bacterial activity and promoted their growth in a type of undesired biofilm. These biofilms have been linked to diseases such as colorectal cancer.

Treatment Reduces Brain Damage from Stroke in Mice

Researchers with the RIKEN Center for Brain Science and Ochanomizu University evaluated a treatment for stroke that appears to decrease the damage to the brain. The scientists studied the approach in mice. They published their research in the Proceedings of the National Academy of Sciences.

The researchers found that they could normalize brain fluids using a combination of drugs called adrenergic receptor (AdR) antagonists, which block the activity of adrenaline in the brain. In the mouse model, it helped motor recovery and reduced cell death. “We know that the water dynamics in the brain immediately during and after a stroke are critical, so we focused on the pathways that move fluids in and out of cells,” stated Hiromu Monai of the RIKEN Center.

Using a cocktail of AdR blockers successfully decreased the area of tissue damage and potassium levels in mice who had strokes. In addition, one to two hours post-stroke, using the AdR blockers was effective in halting the spread of the stroke.

The researchers found that aquaporin 4, a water channel, had lower levels after a stroke. “We think that preserving aquaporin levels is critical to protecting brain tissue during stroke,” Monai stated.

Brain Protein Linked to Obesity Identified

Researchers with the University of Montreal Hospital Research Centre (CRCHUM) identified a brain protein that has a direct influence on neurons that maintain a healthy weight. They published their research in the Journal of Clinical Investigation. The protein is acyl-CoA-binding protein, or ACBP. In April 2015 research, the same group found that the protein allowed astrocytes, which support neuronal function, to communicate variable levels of fatty acids and lipids in the blood to neurons.

“With colleagues from the Universite de Bourdeaux’s NutriNeuro laboratory, we now show that neurons that reduce food intake, known as propiomelanocortin neurons or POMC neurons, are in ‘close communication’ with astrocytes that produce the protein ACBP in a specific area of the brain: the arcuate nucleus of the hypothalamus,” stated Thierry Alquier, associate professor at Universite de Montreal.

The area of the hypothalamus is important in the control of feeding and metabolism. It contains two populations of neurons with two opposition functions, one causing an increase in food intake, the other promoting a decrease of food intake and increase in energy expenditure.

“Genetic mutations explain five to 10% of obesity cases,” stated Alquier. “Among these cases, a large proportion is related to a disruption of this neuronal pathway commonly known as the melanocortin pathway. We observed that the deletion of the ACBP gene in astrocytes of the arcuate nucleus promotes obesity. In mice that were genetically modified to be obese, we observed in the laboratory that injecting them daily with ACBP led to a reduction of food intake and weight loss in the order of 5% over five days, a mechanism that relies on the activation of POMC neurons.”

Using AI to Scale Up Alzheimer’s Research

Researchers at UC Davis and UC San Francisco have taught a computer to detect amyloid plaques in brain tissue images. Amyloid plaques are the most recognized factor in Alzheimer’s disease, although not the only one. In their Nature Communications research, they showed a proof-of-concept machine-learning approach that allowed them to analyze thousands of times more data from human brain tissue samples.

“We still need the pathologist,” stated Brittany N. Dugger, an assistant professor in the UC Davis Department of Pathology and Laboratory Medicine and lead author of the study. “This is a tool, like a keyboard is for writing. As keyboards have aided in writing workflows, digital pathology paired with machine learning can aid with neuropathology workflows.”

The goal of the study was to try and teach a computer to automate the process of identifying and analyzing amyloid plaques in various brain tissues. They developed a “convolutional neural network” (CNN), then worked to device a method that could rapidly annotate or label thousands of images from a library of half-a-million close-up images of tissue from 43 healthy and diseased brain samples.

The tool is available online. They point out that the program doesn’t do the identification better than a human, but it can do it faster and nonstop and is scalable.