They published their work today (July 30) in Nature Communications.

Using advanced imaging techniques, the team developed maps of a mouse brain that illustrate how vascular cells and structures like blood vessels change with age and identified areas that are vulnerable to deterioration. When blood vessels degrade, nerve cells in the brain, called neurons, are starved of energy, causing them to malfunction or die. It can lead to a condition called vascular dementia, the second leading cause of cognitive impairment in older adults, and symptoms like sleep disturbance.

“With something like Alzheimer’s disease, by the time you can see vascular changes and significant brain shrinkage on a MRI, cell death has already occurred. We need to understand how these cells and structures change before a major catastrophe happens,” said Yongsoo Kim, associate professor of neural and behavioral sciences at Penn State College of Medicine and senior author of the study. “This study provides early signs of neurodegenerative disorders, potentially leading to earlier diagnosis, and clues for how we can slow down the aging process and cognitive changes.”

According to Kim, aging is one of the primary factors involved in neurodegenerative disorders.

“Yet, we really don’t have a good baseline understanding of how normal aging itself changes the brain, particularly the brain’s vasculature,” Kim said. And with the aging population in the United States growing, he said it’s critical to understand these changes, especially within the network of blood vessels.

Blood vessels, especially micro-vessels, regulate oxygen and energy supply and waste removal to and from neurons. Despite their importance, Kim said, most existing research focuses on how neuron structure and function degenerates over time, rather than the vasculature. When researchers do study the brain’s vasculature, they’ve primarily examined larger blood vessels or focused on a single, easy-to-access region of the brain, the somatosensory cortex. More importantly, typical neuroimaging techniques, like MRI, don’t provide high enough resolution to see what’s happening in the tiny blood vessels, which make up 80% to 85% of the brain’s vasculature, according to Kim.

Kim and the research team produced a detailed map of the vascular network of the whole mouse brain using two high-resolution 3D mapping techniques: serial two-photon tomography — a technique that creates a series of stacked 2D images — and light sheet fluorescence microscopy, which images intact 3D samples to visualize the whole brain at a single cell-resolution. They imaged the brains of young and old mice to chart vasculature changes across the brain with normal aging.

“Because we’re doing high-resolution mapping with the sufficient resolution, we can reconstruct the whole vascular structure and scan the entire brain to pinpoint areas that undergo selective degeneration with age,” Kim said. “What we found is that the area that most people study showed the least amount of change, whereas profound change happens in areas in the deep areas of the brain. This suggests that we’ve been looking at the wrong area when it comes to aging studies.”

The images showed that changes in the vascular network don’t occur equally across the brain. Rather, they were concentrated in the basal forebrain, deep cortical layers and hippocampal network, suggesting these areas are more vulnerable to vascular degeneration. These regions play a role in attention, sleep, memory processing and storage, among other functions.

As brains age, vascular length and branching density decreases approximately 10%, indicating that there’s a sparser network to distribute blood. Arteries in older brains also appear more twisted compared to those in younger brains, which can impede blood flow, especially to areas further away from the main arteries like the deep cortical layers, Kim explained.

The team also examined functional changes of vasculature and found that the system responds more slowly in older brains. That means that it can’t provide the neurons with energy as quickly and readily as the cells may need. There’s also a loss of pericytes, a type of cell that regulates blood supply and blood vessel permeability, too. As a result, the blood vessels become “leaky,” compromising the blood-brain barrier.

This study builds on the group’s previous research, where they mapped the vasculature of a young mouse brain. Next, they are studying how Alzheimer’s disease-induced changes in the brain influences vascular health and neuronal function. Ultimately, they said they hope their work will lead to treatments for neurodegenerative disorders.

Hannah Bennett, dual medical degree and doctoral degree student, and Steffy Manjila, postdoctoral scholar, co-led the study along with Quingguang Zhang, who was assistant research professor at Penn State at the time of the research and is currently assistant professor at Michigan State University, and Yuan-ting Wu, who was previously research scientist at Penn State and currently project scientist at Cedars-Sinai Medical Center. Other Penn State authors on the paper include: Patrick Drew, professor of engineering science and mechanics, of neurosurgery, of biology and of biomedical engineering and interim director of the Huck Institutes of the Life Sciences; Uree Chon, research technician; Donghui Shin, research technologist; Daniel Vanselow, research project manager; Hyun-Jae Pi, data scientist.

TheNational Institutes of Health and the American Heart Association funded this work.

A team led by Penn State College of Medicine researchers found a way to tease apart genetic and environmental effects of disease risk using a large, nationally representative sample. They found that, in some cases, previous assessments overstated the contribution of one’s genes to disease risk and that lifestyle and environmental factors play a larger role than previously believed. Unlike genetics, environmental factors, like exposure to air pollution, can be more easily modified. That means there are potentially more opportunities to mitigate disease risk. The researchers published their work in Nature Communications.

“We’re trying to disentangle how much genetics and how much the environment influences the development of disease. If we more accurately understand how each contributes, we can better predict disease risk and design more effective interventions, particularly in the era of precision medicine,” said Bibo Jiang, assistant professor of public health sciences at the Penn State College of Medicine and senior author of the study.

The researchers said that in the past, it’s been difficult to quantify and measure environmental risk factors since they can encompass everything from diet and exercise to climate. However, if environmental factors aren’t considered in models of disease risk, analyses may falsely attribute the shared disease risks among family members to genetics.

“People living in the same neighborhood share the same level of air pollution, socioeconomic status, access to health care providers and food environment,” said Dajiang Liu, distinguished professor, vice chair for research, director of artificial intelligence and biomedical informatics at the Penn State College of Medicine and co-senior author of the study. “If we can tease apart these shared environments, what’s remaining could more accurately reflect genetic heritability of disease.”

In this study, the team developed a spatial mixed linear effect (SMILE) model that incorporates both genetics and geolocation data. Geolocation — a person’s approximate geographical location — served as a surrogate measure for community-level environmental risk factors.

Using data from IBM MarketScan, a health insurance claims database with electronic health records from more than 50 million individuals from employer-based health insurance policies in the United States, the research team filtered out information for more than 257,000 nuclear families and compiled disease outcomes for 1,083 diseases. They then augmented the data to include publicly available environmental data, including climate and sociodemographic data, as well as levels of particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2).

The team’s analysis led to more refined estimates of the contributors to disease risk. For example, previous studies concluded that genetics contributed 37.7% of the risk of developing Type 2 diabetes. When the research team reassessed the data, their model, with its consideration of environmental effects, found that the estimated genetic contribution to Type 2 diabetes risk decreased to 28.4%; a bigger share of disease risk can be attributed to environmental factors. Similarly, estimated contribution to obesity risk attributed to genetics decreased from 53.1% to 46.3% when adjusted for environmental factors.

“Previous studies concluded that genetics played a much larger role in disease risk prediction, and our study recalibrated those numbers,” Liu said. “That means that people can stay hopeful even though they have family relatives with Type 2 diabetes, for example, because there’s a lot they can do to reduce their own risk.”

The research team also used the data to quantitatively assess whether two specific pollutants in the air — PM2.5 and NO2 — causally influence disease risks. Previous studies, the researchers said, lump PM2.5 and NO2 together as one collective measure of air pollution. However, what they found in this study was that the two pollutants have different and distinct causal relationships with health conditions. For instance, NO2 is shown to directly cause conditions like high cholesterol, irritable bowel syndrome and both Type 1 and Type 2 diabetes, but not PM2.5. PM2.5, on the other hand, may have a more direct causal effect on lung function and sleep disorders.

Ultimately, the researchers said this model will allow for a more in depth look at questions about why some diseases may be more prevalent in certain geographic locations.

Other Penn State authors on the paper include: Havell Markus and Austin Montgomery, both dual medical degree and doctoral degree students at the Penn State College of Medicine; Laura Carrel, professor of biochemistry and molecular biology; Arthur Berg, professor of public health sciences; and Qunhua Li, professor of statistics. Daniel McGuire, who was a doctoral student in the biostatistics program at the time of the research, co-led the study. Co-author Lina Yang and Jingyu Xu, who were doctoral students in the biostatistics program at the time of the research, also contributed to the paper.

The National Institutes of Health and the Penn State College of Medicine’s artificial intelligence and biomedical informatics pilot funding program supported this work in part. Some of the materials employed in this work were provided by the Center for Applied Studies in Health Economics at the Penn State College of Medicine.

Professor Philip Evans and PhD student Kenny Cheng were experimenting with high-energy plasma to make wood more water-repellent. However, when they applied the technique to the cut ends of wood cells, the surfaces turned extremely black.

Measurements by Texas A&M University’s department of physics and astronomy confirmed that the material reflected less than one per cent of visible light, absorbing almost all the light that struck it.

Instead of discarding this accidental finding, the team decided to shift their focus to designing super-black materials, contributing a new approach to the search for the darkest materials on Earth.

“Ultra-black or super-black material can absorb more than 99 per cent of the light that strikes it — significantly more so than normal black paint, which absorbs about 97.5 per cent of light,” explained Dr. Evans, a professor in the faculty of forestry and BC Leadership Chair in Advanced Forest Products Manufacturing Technology.

Super-black materials are increasingly sought after in astronomy, where ultra-black coatings on devices help reduce stray light and improve image clarity. Super-black coatings can enhance the efficiency of solar cells. They are also used in making art pieces and luxury consumer items like watches.

The researchers have developed prototype commercial products using their super-black wood, initially focusing on watches and jewelry, with plans to explore other commercial applications in the future.

Wonder wood

The team named and trademarked their discovery Nxylon (niks-uh-lon), after Nyx, the Greek goddess of the night, and xylon, the Greek word for wood.

Most surprisingly, Nxylon remains black even when coated with an alloy, such as the gold coating applied to the wood to make it electrically conductive enough to be viewed and studied using an electron microscope. This is because Nxylon’s structure inherently prevents light from escaping rather than depending on black pigments.

The UBC team have demonstrated that Nxylon can replace expensive and rare black woods like ebony and rosewood for watch faces, and it can be used in jewelry to replace the black gemstone onyx.

“Nxylon’s composition combines the benefits of natural materials with unique structural features, making it lightweight, stiff and easy to cut into intricate shapes,” said Dr. Evans.

Made from basswood, a tree widely found in North America and valued for hand carving, boxes, shutters and musical instruments, Nxylon can also use other types of wood such as European lime wood.

Breathing new life into forestry

Dr. Evans and his colleagues plan to launch a startup, Nxylon Corporation of Canada, to scale up applications of Nxylon in collaboration with jewellers, artists and tech product designers. They also plan to develop a commercial-scale plasma reactor to produce larger super-black wood samples suitable for non-reflective ceiling and wall tiles.

“Nxylon can be made from sustainable and renewable materials widely found in North America and Europe, leading to new applications for wood. The wood industry in B.C. is often seen as a sunset industry focused on commodity products — our research demonstrates its great untapped potential,” said Dr. Evans.

Other researchers who contributed to this work include Vickie Ma, Dengcheng Feng and Sara Xu (all from UBC’s faculty of forestry); Luke Schmidt (Texas A&M); and Mick Turner (The Australian National University).