Dr. Swann is a leading expert in epilepsy research and a few years back, his team’s pioneering discoveries resulted in an FDA-approved treatment for severe epilepsy among tuberous sclerosis patients. He and his team have had a longstanding interest and experience in studying infantile spasms, an epileptic disorder diagnosed in roughly 2500 babies in the United States each year.

Early-life brain injuries reduce IGF-1 levels and impair the IGF-1 signaling pathway

“It has been previously reported that IS patients with preexisting brain abnormalities have low levels of IGF-1 in their cerebrospinal fluid and based on that study, we were interested in investigating if IGF-1 levels were altered in the brains of IS animals and patients,” Swann said.

For their investigations, the team used a well-established method to induce spontaneous epileptic spasms in rodents. This methodology, developed in 2008 in the Swann lab, involves chronic infusion of tetrodotoxin (TTX) into the cortex of the infant rat brain, which causes injury at the infusion site and results in spasms that are virtually identical to the those seen in IS patients.

“As is expected after a brain injury, we saw an increase in IGF-1 levels in the non-neuronal support cells (aka glia) at the site of TTX infusion. However, we were most intrigued by the remarkable and widespread decrease in IGF-1 expression in cortical neurons in brain regions adjacent to or further away from the site of TTX injection — a phenomenon that had never been reported before,” Swann said.

Next, the team studied resected cortical tissue from IS patients who had prior perinatal strokes and had undergone surgery to control their intractable seizures. The results were remarkably similar to what they had seen in IS animals.

“More importantly, we found this reduction in cortical levels of IGF-1 had significant consequences in IS animal models because it dampened the overall activity of the IGF-1 molecular signaling pathways that regulate many important biological processes involved in early brain development and neuronal function,” said Dr. Carlos Ballester-Rosado, a postdoctoral associate in the Swann lab and first author of the study.

An IGF-1 analog eliminates infantile spasms in animals

To determine if increasing IGF-1 levels in the cortex of IS animals could ameliorate spasms, the team used a smaller version of IGF-1 that can cross the blood-brain barrier with greater ease than the full-length hormone. The IGF-1 tripeptide they tested is a natural by-product of IGF-1 breakdown that is found normally in the brain. Moreover, this analog has been previously demonstrated to successfully reverse behavioral defects in animal models of other neurodevelopmental disorders such as Rett syndrome and Phelan-McDermid syndrome.

“Using several lines of evidence, we first confirmed that this IGF-1 tripeptide was capable of activating the IGF-1 signaling cascade in mice,” Swann said. “We then found — to our astonishment — that administration of IGF-1 successfully eliminated spasms and an IS-specific chaotic brain activity pattern called hypsarrhythmia in most of the IS animals. We are excited because these findings raise the tantalizing possibility that this IGF-1 analog can be used to treat IS patients in the future.”

Others involved in the study are John Le, Trang Lam, Carrie Mohila, Sandi Lam, Anne Anderson and James Frost. The authors are affiliated with one or more of the following institutions: Cain Foundation Laboratories, the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine. The study was funded by CURE Epilepsy’s Infantile Spasms Initiative, grants from the National Institute of Health (RO1 NS018309, RO1 NS105913 and R61/R33 NS112553) and Intellectual and Developmental Disabilities Centers (1U54 HD083092) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Materials provided by Texas Children’s Hospital. Original written by Rajalaxmi Natarajan. Note: Content may be edited for style and length.

That’s because adding iodide to a water treatment reactor that uses ultraviolet (UV) light and sulfite destroys up to 90% of carbon-fluorine atoms in PFAS forever chemicals in just a few hours, reports a new study led by environmental engineering researchers at UC Riverside. The addition of iodide accelerates the speed of the reaction up to four times, saving energy and chemicals.

“Iodide is really doing some substantial work,” said corresponding author Jinyong Liu, an assistant professor of chemical and environmental engineering. “Not only does it speed up the reaction but it also allows the treatment of a ten times higher concentrations of PFAS, even some very recalcitrant structures.”

Liu’s lab has been working on ways to destroy PFAS through photochemical reactions since 2017. The new method has already attracted interest from industry and Liu’s group is partnering with companies to conduct pilot tests.

Synthetic chemicals known as PFAS contain multiple very strong carbon-fluorine bonds. Widespread use of these nonbiodegradable compounds in countless products since the 1940s has contaminated water supplies across America, with various negative health effects on human and animals. Because the carbon-fluorine bond is very hard to break, PFAS pass through most water treatment systems unchanged.

Photochemical degradation by UV light and sulfite (SO₃²⁻) is, to date, one the most effective ways to break PFAS down. The original process used a lot of electricity because the chemical reactions occurred slowly. It also left multiple carbon-fluorine bonds remaining in the degradation products, with unknown health effects.

Last year, the researchers reported that oxidation treatments before and after the UV/sulfite treatment can achieve almost 100% destruction of carbon-fluorine bonds in various major PFAS pollutants.

In the new work, the researchers added iodide to the UV/sulfite system to treat a particularly stubborn four-carbon PFAS molecule called perfluorobutane sulfonate (PFBS), which degrades poorly in the original UV/sulfite setting. The iodide accelerated the reaction and completely removed PFBS within 24 hours.

As expected, the UV/sulfite+iodide system also degraded other PFAS, such as the frequently reported eight-carbon PFOA and PFOS, with ease. The addition of iodide also enabled the system to destroy concentrated PFAS in brine solution, which is a practical challenge for groundwater remediation. Ion-exchange systems are used to clean the groundwater, but the PFAS chemicals captured in the resin need to be washed out and destroyed in a cost-effective way.

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Materials provided by University of California – Riverside. Original written by Holly Ober. Note: Content may be edited for style and length.

The study, led by UBC faculty of forestry member Arthur Bass and using data generated by the Strategic Salmon Health Initiative, assessed dozens of pathogens in thousands of Chinook and Coho salmon sampled over a decade along the B.C. coast.

For the first time ever, researchers were able to identify the pathogens most closely linked to survival of free-ranging Pacific salmon in the ocean: Tenacibaculum maritimum, a bacterium that causes ulcerative disease in salmon and other cultured marine fish worldwide; and piscine orthoreovirus (PRV), a virus that causes disease in Pacific and Atlantic salmon worldwide, but whose impact on salmon in B.C. is vigorously debated.

“This is the first empirical evidence that PRV is negatively impacting wild Pacific salmon in B.C.,” says Dr. Bass, a postdoctoral researcher at UBC’s Pacific Salmon Ecology Conservation Lab. “These two pathogens are common on salmon farms in B.C., and recent studies provide evidence of transmission from farms to wild salmon.”

“Many studies show that high ocean temperatures impact salmon survival, but this new research shows that in some cases pathogen presence can be more important,” notes the study senior author Kristin Miller-Saunders, a molecular genetics scientist with Fisheries and Oceans Canada (DFO) and an adjunct professor of fisheries at UBC.

The research was funded by the Pacific Salmon Foundation, Genome BC and DFO and published today in FACETS.

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Materials provided by University of British Columbia. Note: Content may be edited for style and length.

Previously, scientists linked high-fat diets and elevated blood cholesterol with increased susceptibility to infection and lowered immune response. For example, obesity is a well-known risk factor for severe disease in COVID and influenza. But few studies have separated out the contribution of cholesterol in these infections, and none have delineated the effect of dietary cholesterol.

“We knew high serum cholesterol levels can lead to higher risk of sepsis in influenza infections and that statins — cholesterol-lowering medications — can improve survival during influenza pneumonia, SARS-CoV-2 infection, and sepsis. But it wasn’t clear whether or how dietary cholesterol was involved,” says Allison Louie, lead author on the Journal of Immunology study and doctoral student in the Neuroscience Program at Illinois.

Cholesterol is essential in the body. It’s part of our cell membranes, helps us make hormones and vitamin D, and allows for proper immune cell function. Our bodies manufacture it for us, requiring little to come in through dietary sources. In fact, for healthy people, dietary cholesterol does not substantially affect circulating cholesterol levels nor increase risk of cardiovascular disease. That’s part of the reason limits on cholesterol intake were lifted from the Dietary Guidelines for Americans in 2015.

But when it comes to infectious disease in mice, Louie’s study suggests dietary cholesterol may make a difference, even without increasing dietary fat.

Louie, along with co-authors Andrew Steelman and Joseph Tingling, fed mice a standard rodent chow or an identical diet supplemented with 2% cholesterol. After five weeks on the diets, mice were infected with a mouse-adapted human influenza A virus. The research team tracked disease progression, including weight loss, food intake, and sickness behavior. They also tracked serum cholesterol levels and immune responses and measured viral load in the lungs at multiple time points over the course of the infection.

“Across four cohorts, the cholesterol-fed mice had consistently higher morbidity,” Louie says. “They exhibited greater weight loss and sickness behavior.”

Because viruses also require cholesterol for cell entry and replication, there was a chance the high-cholesterol diet would boost viral load in the lungs. But that’s not what the researchers found.

“Our plaque assay did not show a significant difference in viral load in the lungs of the two groups of mice,” says Tingling, a postdoctoral researcher in the Department of Animal Sciences at Illinois. “It’s very important to consider not just the infectious agent, but the host immune system.”

Speaking of the host, the researchers determined mice fed a high-cholesterol diet were sicker because their immune systems went awry. Fat can have an immunosuppressive effect, which is detrimental during the course of an infection. But an underactive immune system is not what the researchers observed in the cholesterol-fed mice. Instead, cholesterol increased the number of cytokine-producing immune cells in the lungs.

“A so-called cytokine storm during severe disease results in excessive inflammation that can be damaging to the host. Along those lines, we found that more cytokine-producing cells had infiltrated the lungs of the mice fed cholesterol, which may have contributed to them being sicker,” Louie says. “It’s a double-edged sword. You want to be able to mount an effective immune response, but excessive inflammation is detrimental.”

Unfortunately, the effects of dietary cholesterol on influenza morbidity lasted long after mice stopped eating it. The researchers took mice that consumed a high-cholesterol diet initially and then gave them a normal diet for five weeks. When those mice were exposed to influenza, they still got sicker than mice that had never consumed a high cholesterol diet.

“We were thinking this dietary component is a highly modifiable factor. Perhaps it would only have a transient effect. But ultimately we found that five additional weeks on a normal diet was not enough time to fully reverse the detrimental effects of cholesterol,” Louie says.

Surprisingly, inflammatory changes in the lungs were detectable in the high-cholesterol mice even before they were infected with influenza.

“Some of the changes in the lungs’ immune function were already present before infection. It would be interesting to see exactly how dietary cholesterol increased inflammation prior to infection,” says corresponding author Steelman, associate professor in the Department of Animal Sciences, the Neuroscience Program, and the Division of Nutritional Sciences at Illinois.

“Nevertheless, our data collectively show that dietary cholesterol increased morbidity in influenza-infected mice. The response appeared to be a result of an aberrant immune response occurring in the lungs rather than an effect of the virus itself. These results demonstrate the need to consider how host factors contribute to disease outcome.”

Department of Animal Sciences and the Division of Nutritional Sciences are in the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign.

Led by Huanyu “Larry” Cheng, assistant professor of engineering science and mechanics at Penn State, the researchers published their sensor designs, which build on previous models, and results in ACS Applied Materials and Interfaces.

The sensors monitor nitrogen dioxide, either from breath if attached under the nose, or from perspiration, if attached elsewhere on the body. Unlike taking blood samples, the direct skin attachment allows for continuous, long-term monitoring of the gas.

Cheng explained that while similar sensors exist, a key differentiator of the new design is breathability.

“The commonly used substrate materials for gas sensors are flexible, but not porous,” he said. “The accumulation of water moisture from the skin surface can potentially lead to irritation or damage to the skin surface. We need to make sure the device can be porous so that moisture can go through the sensor without accumulation on the surface.”

The researchers created the new sensors using a fabrication method known as laser direct writing.

“Laser direct writing is similar to additive manufacturing in that it is easy to set up and low cost, and the laser is widely available,” Cheng said. “The process is relatively robust, rapid and could be scaled up to large-scale manufacturing production.”

Cheng and his team integrated a type of material known as block copolymers with resin to laser write sensors with the desired breathability.

“Block copolymer integration goes beyond the materials we have been using, so we explored extending the substrate material from the typical thin film to virtually anything,” Cheng said. “That can give us breathability and tunability of the pore size.”

Cheng said that the sensor could monitor conditions such as chronic obstructive pulmonary disease, which nitrogen dioxide can cause or make worse. He also noted that while the sensors were developed specifically to detect nitrogen dioxide, they could potentially detect a variety of gases and biomarkers — to determine glucose levels to monitor diabetes, for example, or to identify hazards in industrial or combat settings.

“The sensors can also be useful for monitoring gas in the environment,” he said. “We could monitor air quality and inform patients of potential concerns about too much exhaust from cars, for example. Then, they could use that information to avoid certain areas on certain days.”

Other authors on this paper are Li Yang, Huadong Ji, Chuizhou Meng, Guanhao Zheng, Xue Chen, Guangyu Niu, Jiayi Yan, Ye Xue and Shijie Guo, all of Hebei University of Technology in Tianjin, China; and Yuhang Li of Beihang University in Beijing. The National Natural Science Foundation of China, the Key Research and Development Project of Hebei Province, the National Science Foundation, the National Institutes of Health and Penn State funded this work.

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Materials provided by Penn State. Original written by Sarah Small. Note: Content may be edited for style and length.