Culture

Astronomers find a golden glow from a distant stellar collision

image: In this animated series of images captured by NASA's Hubble Space Telescope, a newly confirmed kilonova (red arrow) -- a cosmic explosion that creates massive amounts of gold and platinum -- rapidly fades from view as the explosion's afterglow diminishes over a period of 10 days. The kilonova was originally identified as a standard gamma-ray burst, but a UMD-led team of astronomers recently revisited the data and found evidence for a kilonova.

Image: 
NASA/ESA/E. Troja

On August 17, 2017, scientists made history with the first direct observation of a merger between two neutron stars. It was the first cosmic event detected in both gravitational waves and the entire spectrum of light, from gamma rays to radio emissions.

The impact also created a kilonova--a turbocharged explosion that instantly forged several hundred planets' worth of gold and platinum. The observations provided the first compelling evidence that kilonovae produce large quantities of heavy metals, a finding long predicted by theory. Astronomers suspect that all of the gold and platinum on Earth formed as a result of ancient kilonovae created during neutron star collisions.

Based on data from the 2017 event, first spotted by the Laser Interferometer Gravitational-wave Observatory (LIGO), astronomers began to adjust their assumptions of how a kilonova should appear to Earth-bound observers. A team led by Eleonora Troja, an associate research scientist in the University of Maryland's Department of Astronomy, re-examined data from a gamma-ray burst spotted in August 2016 and found new evidence for a kilonova that went unnoticed during the initial observations.

NASA's Neil Gehrels Swift Observatory began tracking the 2016 event, named GRB160821B, minutes after it was detected. The early catch enabled the research team to gather new insights that were missing from the kilonova observations of the LIGO event, which did not begin until nearly 12 hours after the initial collision. Troja and her colleagues reported these new findings in the journal Monthly Notices of the Royal Astronomical Society on August 27, 2019.

"The 2016 event was very exciting at first. It was nearby and visible with every major telescope, including NASA's Hubble Space Telescope. But it didn't match our predictions--we expected to see the infrared emission become brighter and brighter over several weeks," said Troja, who also has an appointment at NASA's Goddard Space Flight Center. "Ten days after the event, barely any signal remained. We were all so disappointed. Then, a year later, the LIGO event happened. We looked at our old data with new eyes and realized we had indeed caught a kilonova in 2016. It was a nearly perfect match. The infrared data for both events have similar luminosities and exactly the same time scale."

The similarities between the two events suggest that the 2016 kilonova also resulted from the merger of two neutron stars. Kilonovae may also result from the merger of a black hole and neutron star, but it is unknown whether such an event would yield a different signature in X-ray, infrared, radio and optical light observations.

According to Troja, the information collected from the 2016 event does not contain as much detail as the observations of the LIGO event. But the coverage of those first few hours--missing from the record of the LIGO event--revealed important new insights into the early stages of a kilonova. For example, the team got their first look at the new object that remained after the collision, which was not visible in the LIGO event data.

"The remnant could be a highly magnetized, hypermassive neutron star known as a magnetar, which survived the collision and then collapsed into a black hole," said Geoffrey Ryan, a Joint Space-Science Institute (JSI) Prize Postdoctoral Fellow in the UMD Department of Astronomy and a co-author of the research paper. "This is interesting, because theory suggests that a magnetar should slow or even stop the production of heavy metals, which is the ultimate source of a kilonova's infrared light signature. Our analysis suggests that heavy metals are somehow able to escape the quenching influence of the remnant object."

Troja and her colleagues plan to apply the lessons they learned to re-evaluate past events, while also improving their approach to future observations. A number of candidate events have been identified with optical light observations, but Troja is more interested in events with a strong infrared light signature--the telltale indicator of heavy metal production.

"The very bright infrared signal from this event arguably makes it the clearest kilonova we have observed in the distant universe," Troja said. "I'm very much interested in how kilonova properties change with different progenitors and final remnants. As we observe more of these events, we may learn that there are many different types of kilonovae all in the same family, as is the case with the many different types of supernovae. It's so exciting to be shaping our knowledge in real time."

Credit: 
University of Maryland

Streaks in aurora found to map features in earth's radiation environment

image: This illustration shows the white-light observations of the fine structure in the aurora superimposed over Alaska. The dots signifying electrons are color coded to show their origins, with red dots indicating electrons from the radiation belts and blue from further out.

Image: 
NASA/Google Earth/Nithin Sivadas

A special kind of streaked aurora has been found to track disturbances in near-Earth space from the ground. Known as structured diffuse aurora, it was recently discovered, with the help of NASA spacecraft and instruments, that these faint lights in the night sky can map the edges of the Van Allen radiation belts -- hazardous concentric bands of charged particles encircling Earth.

When the Van Allen belts undulate in shape and size -- which they do in response to incoming radiation from the Sun as well as changes from Earth below -- they can envelop satellites in unexpected radiation. The new discovery will help us better track the edges of the belts -- and the more we know about how the belts are changing, the more we can mitigate such effects.

Credit: 
NASA/Goddard Space Flight Center

The positives of climate change? WVU research shows agricultural, economic possibilities

image: Jason Hubbart, director of the WVU Institute of Water Security and Science, conducts water testing at West Run Creek for research.

Image: 
Greg Ellis/West Virginia University

Depending on your side of the aisle, climate change either elicits doomsday anxiety or unabashed skepticism.

Jason Hubbart, director of Institute of Water Security and Science at West Virginia University, takes a more centered approach.

He’s studied the undisputable changing patterns in West Virginia’s climate. And, believe it or not, there is at least one silver lining stemming from changing climate, he insists: The growing season is getting longer.

“Our future climates in West Virginia are likely to be more conducive to agricultural production,” said Hubbart, a professor of hydrology and water quality in the Davis College of Agriculture, Natural Resources and Design. “We should plan for that now.”

In research published in Regional Environmental Change, and the journals Water and Climate, Hubbart found that, between 1900 and 2016, maximum temperatures in West Virginia trended downward, average minimum temperatures ascended and annual precipitation increased. Specifically, precipitation increased about an inch each of the last few decades.

In other words, West Virginians are now, on average, seeing cooler summers, warmer winters and wetter weather.

Corresponding with those trends, big changes have occurred in agriculture. Yield for hay and corn, which have historically been bread-and-butter resources for the state, have increased, yet 23 percent slower than the national average; however, other crops, including winter wheat and soybeans, have increased yields 15 percent faster than the national average.

Based on his findings, “it’s time to rethink farming in West Virginia,” said Hubbart, who grew up on a 2,000-acre dairy farm near Spokane, Washington.

Hubbart breaks down why traditional West Virginia crops are floundering while others, previously not prominent, have gained potential.

“Some areas of West Virginia are too drenched or flooded all the time,” he said. “Because it’s wetter, we’ve seen a decline in crops like hay and corn.”

An uptick in humidity – a result of climate change in many regions – plays a part in the dwindling performance of traditional West Virginia crops. More humidity lowers vapor-pressure deficit, which is the difference between the amount of moisture in the air and how much moisture the air can hold (i.e. saturation).

When the air is saturated, water can condense out to form clouds, turn into precipitation and create dew or films of water over a plant’s leaves. More importantly, when the air is saturated (approaching 100 percent humidity), plants have a much more difficult time transpiring (moving water from the leaf to atmosphere). Therefore, the plants also have difficulty staying cool, transporting nutrients and photosynthesizing. For many historic agricultural crops, future climates may result in lower productivity.

Corn and alfalfa, for instance, need a lot of water. Those plants use energy to create sugars and biomass. If it gets too hot, productivity can slow because they cannot move water up the plant and out the stomates, Hubbart explained. Ultimately, though West Virginia is seeing more precipitation, the increased humidity slows the movement of water from the plant to the atmosphere.

Yet that doesn’t mean death to West Virginia agriculture. Crops that don’t require as much water (through transpiration), or thrive in short winters, long summers or moderate temperatures, could help turn the state around, Hubbart believes.

The winter season has shrunk by as much as 20 days, according to Hubbart’s research, and the minimum (and winter) temperatures have become warmer. The growing season itself has increased by approximately 13 days.

“Winter wheat and soy bean crops are just a couple of examples of future agricultural investment,” Hubbart said. “Those crops, and many broadleafs do well in short winters. Basil, specialty teas, specialty vegetables, those are plants that have had trouble growing here historically, but now, and in the future, they may fare better.

“We can diversify our crops more. West Virginia should be thinking strategically about which crops to grow in what locations.”

Outcomes in his research also suggest the possibility of double-cropping, meaning that the growing seasons are extending long enough to raise one crop and harvest it and then raise another crop and harvest it, too, within the same year.

“Doing that, obviously, increases economic revenue and provides local food supplies that could greatly improve access to fresh vegetables to our citizens,” Hubbart said. “That’s more than just a bit of good news.”

Hubbart’s findings come from more than 90 years’ worth of observed weather data from climate stations on the ground throughout West Virginia and Appalachia. Whereas some research relies on climate models utilizing information from more distant locations and predictions based on those models that often aren’t accurate, these findings are based on actual observed long-term West Virginia data, he said.

While other climate research predicts drier climates and the emergence of food deserts, Hubbart’s research indicates quite the opposite.

“West Virginia is a beautiful state with so much to look forward to,” he said. “Our great scientists are making incredible progress in agriculture, food deserts, agricultural economics, etc. We need to celebrate our current successes and how we can use those successes in what I view as a very bright agricultural future for our state.”

“My results indicate that future climates will facilitate higher productivity and new crops, both of which could create an economic boom for West Virginia, reduce food desert issues and broadly improve the human condition in our state.”

Journal

Regional Environmental Change

Credit: 
West Virginia University

Computational approach speeds up advanced microscopy imaging

image: The researcher compared two-photon microscopy images of a pollen grain using traditional raster scanning (a) and their new compressive imaging approach (b). The raster-scanning imaging time was 2.2 seconds while the compressive imaging time required only 0.55 seconds.

Image: 
Shih-Chi Chen from The Chinese University of Hong Kong

WASHINGTON -- Researchers have developed a way to enhance the imaging speed of two-photon microscopy up to five times without compromising resolution. This record-fast imaging speed will allow scientists to observe biological phenomena that were previously too fleeting to image with current state-of-the-art advanced microscopy.

In The Optical Society (OSA) journal Optics Letters, researchers led by Shih-Chi Chen from The Chinese University of Hong Kong describe how they combined a computational imaging approach known as compressive imaging with a faster scanning method. They used the new method to acquire two-photon microscopy images of a pollen grain in less than one second. This would take five times as long using the traditional approach.

"This new compressive sensing-based two-photon microscopy method will be useful for visualizing a neural network or monitoring activity from hundreds of neurons simultaneously," said Chenyang Wen, first author of the paper. "Typically, neurons transmit signals on a time scale of 10 milliseconds, which conventional systems are too slow to follow."

Speedier scanning
Two-photon microscopy works by delivering ultrafast pulses of infrared laser light to the sample where it interacts with tissue or fluorescent labels that emit signals used to create an image. It is extensively used for biology research because of its ability to produce high-resolution, 3D images up to a depth of one millimeter. These advantages, however, come with a limited imaging speed because the low-light conditions call for point detectors that require point-by-point image acquisition and reconstruction.

To speed up imaging, the researchers previously developed a multi-focus laser illumination method that uses a digital micromirror device (DMD), a type of low-cost light scanner typically used in projectors. "It was thought that these DMDs could not work with ultrafast lasers," said Chen. "However, we recently addressed this issue, which has enabled application of DMDs in ultrafast laser applications that include beam shaping, pulse shaping, fast scanning and two-photon imaging."

The DMD generates five to 30 points of focused laser light on randomly selected locations within a specimen. The position and intensity of each point of light are controlled by a binary hologram that is projected onto the device. During each measurement, the DMD reflashes the hologram to change the position of each focus and records the intensity of the two-photon fluorescence with a single-pixel detector. Although, in many ways, DMD multi-focus scanning is more flexible and faster than traditional raster scanning, the speed is still limited by the rate at which the device can form light patterns.

Combining methods brings faster imaging
In the new work, the researchers further increase the imaging speed by combining multi-focus scanning with compressive sensing. This computational approach enables image reconstruction with fewer exposures because it carries out sampling and image compression in a single step and then uses an algorithm to fill in the missing information. For two-photon microscopy, it allows a specimen to be reconstructed using 70 to 90 percent fewer exposures than traditional approaches.

After conducting a simulation experiment to demonstrate the new method's performance and to identify optimal parameters, the researchers tested it with two-photon imaging experiments. These experiments demonstrated the technique's ability to produce high-quality 3D images with high imaging speeds from any field of view. For example, they were able to acquire images from five layers in a pollen grain, with each layer measuring 100 × 100 pixels, in just .55 seconds. The same images acquired with raster scanning took 2.2 seconds.

"We achieved a 3 to 5 times enhancement in imaging speed without sacrificing the resolution when imaging arbitrarily selected regions in 3D specimens," said Wen. "We believe this new compressive sensing-based approach will be useful to use with approaches such as optogenetics in which light is used to control neurons and will lead to new discoveries in biology and medicine."

The researchers are working to further improve the speed of the reconstruction algorithm and image quality. They also plan to use the DMD platform with other advanced imaging techniques such as wave front correction, which allows deep tissue imaging.

Credit: 
Optica

Pregnant women of color experience disempowerment by health care providers

image: Women of color perceive their interactions with doctors, nurses and midwives as being misleading, with information being "packaged" in such a way as to disempower them by limiting maternity healthcare choices for themselves and their children.

Image: 
Altman et al. <em>Social Sciences and Medicine</em>

A new study finds that women of color perceive their interactions with doctors, nurses and midwives as being misleading, with information being "packaged" in such a way as to disempower them by limiting maternity healthcare choices for themselves and their children.

"Given the significant birth-related disparities faced by women of color, particularly black women, this study illuminates a previously undescribed aspect of the patient-provider interaction," said University of Washington assistant professor Molly Altman, lead author of the study published online in the journal Social Science & Medicine.

"How providers shared or didn't share appropriate information about options, risks and possible outcomes was perceived as biased and dependent on whether providers saw them as individuals capable of making good decisions," said Altman. Now at the UW School of Nursing, Altman conducted the research while a postdoctoral fellow at the University of California San Francisco as part of its California Preterm Birth Initiative.

The study participants said that while they wanted complete, truthful and comprehensive information about their care and options available, they felt information was "packaged" in a way that reflected what the provider thought the patient should do, based on bias, and was "disrespectful."

One participant said she felt like her providers were "harassing" and "bullying" her to get tests she didn't want. Another said she wanted to "do a little bit more research" into vaccinations before getting them for her children, and said her provider "was like, 'Well, I thought that you cared about your children. But if that's not the case, then feel free to go.'"

Researchers interviewed 22 self-identified women of color from the San Francisco Bay Area who had given birth within the previous year. The interviews were open-ended discussions of the participants' experiences in pregnancy, birth and postpartum care and took place between September 2015 and December 2017. The researchers point out in their paper that they used a method of analysis that "acknowledges the subjective and involved nature of the researcher in relation to the participant" to account for the interpersonal nature of the research.

"The results of our study were not surprising in the sense that communities of color have long known that providers often use their power to influence health-related communication and decision-making," Altman said. However, she added, "given existing evidence of the impacts of implicit bias and racism on birth outcomes, this study provides a potential mechanism for how this association occurs."

The authors explain that while providers have to consider health literacy of patients and tailor information to make it understandable, there is a difference between providing information in understandable language and packaging information based on prejudice and assumptions, or not providing information at all.

One participant said that during a postpartum hemorrhage, she received no information about what was happening to her and was treated as if she were not part of the situation.

"It was scary because I didn't know what was happening, and, I mean, it was obvious that it was a serious issue because of, like, the look on everyone's face and, like, how -- how no one was even talking to me," the participant said.

Another participant explained that when she told her health care providers she was a student at the University of California, Berkeley, they treated her differently.

"They're like, 'Oh, maybe she's not a crazy black woman,' or something, you know? ... It just makes me feel weird because, one, I feel like I'm accessing on like a certain type of privilege. And I feel like a part of me does it on purpose because I know that they're going to treat me better after I say that," the participant said.

The researchers hope the study provides evidence that will lead to improved provider training in power differentials, informed consent and providing respectful care.

"Our study is one of the first to evaluate how information and power are exchanged between providers and patients from the perspective of the people we serve," said Monica McLemore, the study's co-author and an associate professor at the UCSF School of Nursing. "I believe these data are critical in developing new models of partnership, specific to how black women and other people with the capacity for pregnancy want and need to receive information that is essential for their care and decision-making."

Credit: 
University of Washington

Unraveling the history and science behind ancient decorative metal threads

image: This colorized microscopy image of an 18th century metal thread reveals it is made of a piece of metal wrapped around a silk core; inset shows relative amounts of silver and gold/silver alloy. Scale bar = 100 microns.

Image: 
Aleksandra Popowich and Edward Vicenzi

SAN DIEGO, Aug. 27, 2019 -- When it comes to historical fashion, nothing stands out more than an item woven with shiny metal threads. These threads have been woven into textiles since ancient times and have been used by cultures around the world. However, the historical record has limited insight into how these materials were made, and conservation efforts limit scientists' ability to obtain samples because many methods are destructive. Today, researchers report their progress toward a new, less damaging methodology for analyzing metal threads.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"This project began when we were asked to investigate the metal threads of a 14th century Italian textile using a proteomics-based approach," says Caroline Solazzo, Ph.D., who is one of the project's principal investigators. Her team published a study last year characterizing the protein-containing membranes and adhesives in the threads of this artifact, which were made from animal products such as cow hide and pig intestine. Now, the team is reporting on their investigation into the exact composition of metal fibers of this and other historical objects.

"Conservation science is a unique area of chemistry research," says Aleksandra Popowich, Ph.D., who is presenting the work at the meeting. "We are using microscopy techniques that allow us to build a 3D view of the threads, so we can see things like layering and micro-structure that give us insight into when and how the fibers were made." Both Solazzo and Popowich are researchers at the Smithsonian's Museum Conservation Institute, a center for specialized technical collections research and conservation of artistic, anthropological, biological and historical artifacts.

While decorative metal threads have been a subject of historical research interest for decades, studies to determine their manufacture and makeup have relied on cross-section analysis to view the internal metal structure. The current study, however, was driven by the desire to maintain the integrity of artifacts.

For this particular work, Popowich and her Smithsonian colleagues Thomas Lam, Ph.D., and Edward Vicenzi, Ph.D., obtained 30 samples from the Fashion Institute of Technology. The samples originated from Europe, Asia and the Middle East, and some of them were nearly 1,000 years old. The types of threads were diverse; some were strips of metal, others were strips of paper wrapped around fibers. Many of the pieces were religious textiles, such as vestments, demonstrating the cultural and historical importance of metal threadwork.

To get a closer look, the researchers developed a strategy that combined energy dispersive X-ray spectroscopy and correlated micro X-ray fluorescence. Together, the methods provided a high-resolution map of the threads' elemental composition and thickness. These techniques only required a few micrograms of material, leaving most of the threads intact for future conservation efforts.

The resulting surface images and cross-sections showed that most threads had a combination of gold, silver and sometimes copper or zinc, creating a layered structure that highlighted the intricacy of the craftsmanship. The researchers learned that some thread-making techniques vary by culture, but other methods did not change much over time. For example, data from two French threads, one from the 16th century and one from the 18th century, showed that the process of rolling super-thin metal wires and wrapping them around a core material was largely unchanged between those years. In addition, the measurements taken using this method align with historic sources and data from computer simulations.

With this pilot investigation completed, the researchers plan to further develop this strategy to the point where they do not need to destroy a piece of the sample at all. This advance could open up the list of artifacts for study to include those that are too culturally important to damage for the sake of research. Such a method could also expand their work to include other materials, such as gilt leather, tapestries or gilded furniture.

Credit: 
American Chemical Society

Smartphone-based device for detecting norovirus, the 'cruise ship' microbe

image: A sensitive new device can detect tiny amounts of norovirus in water.

Image: 
American Chemical Society

SAN DIEGO, Aug. 27, 2019 -- Made infamous by outbreaks on cruise ships, norovirus can really ruin a vacation, causing severe vomiting, diarrhea and stomach pain. But the highly infectious virus can also strike closer to home, with water- and foodborne outbreaks occurring in municipal water systems, schools and restaurants. Today, researchers report a sensitive, portable device that can detect as few as a handful of norovirus particles in water.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

A brand-new video on the research is available at http://www.acs.org/HLS_Norovirus_Detector.

"It only takes a very small number of norovirus particles to cause an infection in humans, so we need a really sensitive detection method," says Jeong-Yeol Yoon, Ph.D., who led the team. "Also, scientists aren't able to culture norovirus in the lab, and available antibodies to the pathogen aren't very strong." As a result, detecting very small amounts of norovirus in water or food samples typically involves a polymerase chain reaction (PCR)-based method, which takes several hours and must be conducted in a lab by trained personnel.

In previous work, Yoon and his colleagues at the University of Arizona developed a smartphone-based device that could detect low levels of norovirus by measuring the light scattered from virus-bound polystyrene beads in a paper microfluidic chip. "Even though our detection limit was really low, the problem was that norovirus can be infectious at even lower concentrations," Yoon says. "When we talked about this work at conferences, the feedback we received was that we need to provide an even easier method that can detect much lower concentrations of virus."

So the team went back to the lab and developed a new approach that uses fluorescence, rather than light scattering, to detect norovirus. The researchers converted an ordinary smartphone into a fluorescence microscope by attaching a commercially available light microscope accessory, a separate light source and two band-pass filters. To a channel of their paper microfluidic chip, they added a water sample containing norovirus. Then, the researchers added a suspension of fluorescent beads with antibodies against norovirus attached to them. The capillary action of the paper caused the two liquids to flow and mix. Each individual norovirus particle bound to multiple fluorescent beads via their attached antibodies, causing the beads to aggregate and produce a much larger size of fluorescent image.

The team snapped photos of the chip with their smartphone-based fluorescence microscope, and an app calculated norovirus concentrations from the pixel count of the images. "The lowest detection limit corresponded to about 5 or 6 norovirus particles per sample, so it's very close to the single-virus level," Yoon says. Because as few as 10 virus particles can cause illness in people, the new method is sensitive enough for practical applications.

Recently, Yoon and colleagues made the system more compact and handheld by enclosing the fluorescent microscope, light source and optical filters in a 3D-printed case. They also developed a cloud-computing app to analyze the large images and send the results back to the smartphone. In addition, they found a way to concentrate samples within the paper chip so they can analyze much larger sample volumes.

The device could detect miniscule amounts of norovirus in both purified water and reclaimed wastewater, which is very dirty. Tap water, on the other hand, was prone to error. "We believe that the chlorine in tap water is affecting the assay," Yoon says. "We don't think it will be a problem to treat the water to remove chlorine before performing our method." Yoon envisions that municipal water systems staff could use the device and app to check for norovirus in the water supply. To test use of the assay in the field, the team is collaborating with Kelly Reynolds, Ph.D., at the same institution, as well as Tucson Water.

Now, Yoon and colleagues are working on using their smartphone-based device for diagnosing norovirus infections in patients at an earlier stage than is currently possible. To do this, they plan to analyze fecal samples. "When norovirus reaches levels detectable by other methods, the person is already seriously ill," Yoon says. "But if we can detect the virus earlier, they can receive medical care sooner." Early detection might also help curb the spread of disease in isolated, crowded situations like cruise ships, where distinguishing between a run-of-the-mill upset stomach and a norovirus infection could guide quarantine efforts or expedite getting a passenger to port for treatment.

Credit: 
American Chemical Society

Nanoparticles could someday give humans built-in night vision

image: Organic nanoparticles in a vial convert invisible near-infrared light to intense blue light, which can easily be seen by human eyes.

Image: 
Gang Han

SAN DIEGO, Aug. 27, 2019 -- Movies featuring heroes with superpowers, such as flight, X-ray vision or extraordinary strength, are all the rage. But while these popular characters are mere flights of fancy, scientists have used nanoparticles to confer a real superpower on ordinary mice: the ability to see near-infrared light. Today, scientists report progress in making versions of these nanoparticles that could someday give built-in night vision to humans.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"When we look at the universe, we see only visible light," says Gang Han, Ph.D., the project's principal investigator, who is presenting the work at the meeting. "But if we had near-infrared vision, we could see the universe in a whole new way. We might be able to do infrared astronomy with the naked eye, or have night vision without bulky equipment."

The eyes of humans and other mammals can detect light between the wavelengths of 400 and 700 nanometers (nm). Near-infrared (NIR) light, on the other hand, has longer wavelengths -- 750 nm to 1.4 micrometers. Thermal imaging cameras can help people see in the dark by detecting NIR radiation given off by organisms or objects, but these devices are typically bulky and inconvenient. Han and his colleagues wondered whether they could give mice NIR vision by injecting a special type of nanomaterial, called upconversion nanoparticles (UCNPs), into their eyes. These nanoparticles, which contain the rare-earth elements erbium and ytterbium, can convert low-energy photons from NIR light into higher-energy green light that mammalian eyes can see.

In work published earlier this year, the researchers, who are at the University of Massachusetts Medical School, targeted UCNPs to photoreceptors in mouse eyes by attaching a protein that binds to a sugar molecule on the photoreceptor surface. Then, they injected the photoreceptor-binding UCNPs behind the retinas of the mice. To determine whether the injected mice could see and mentally process NIR light, the team conducted several physiological and behavioral tests. For example, in one test, the researchers placed the mice into a Y-shaped tank of water. One branch of the tank had a platform that the mice could climb on to escape the water. The researchers trained the mice to swim toward visible light in the shape of a triangle, which marked the escape route. A similarly lit circle marked the branch without a platform. Then, the researchers replaced the visible light with NIR light. "The mice with the particle injection could see the triangle clearly and swim to it each time, but the mice without the injection could not see or tell the difference between the two shapes," says Han. A video of this work, posted by Han's institution, can be viewed here.

Although the UCNPs persisted in the mice's eyes for at least 10 weeks and did not cause any noticeable side effects, Han wants to improve the safety and sensitivity of the nanomaterials before he contemplates trying them out in humans. "The UCNPs in our published paper are inorganic, and there are some drawbacks there," Han says. "The biocompatibility is not completely clear, and we need to improve the brightness of the nanoparticles for human use." Now, the team is experimenting with UCNPs made up of two organic dyes, instead of rare-earth elements. "We've shown that we can make organic UCNPs with much improved brightness compared with the inorganic ones," he says. These organic nanoparticles can emit either green or blue light. In addition to having improved properties, the organic dyes could also have fewer regulatory hurdles.

One of the next steps for the project might be translating the technology to man's best friend. "If we had a super dog that could see NIR light, we could project a pattern onto a lawbreaker's' body from a distance, and the dog could catch them without disturbing other people," Han says. Superhero powers aside, the technology could also have important medical applications, such as treating diseases of the eye. "We're actually looking at how to use NIR light to release a drug from the UNCPs specifically at the photoreceptors," Han says.

Credit: 
American Chemical Society

Skin creams aren't what we thought they were

image: Model of the molecular structure of a cream, with the atoms of a surfactant and co-surfactant in the lamella shown in light and dark gray in the middle of the image, and atoms of a preservative in green and light gray along the edges of the image. The red and orange spheres are oxygen and sodium atoms, respectively.

Image: 
David Barlow and Delaram Ahmadi

SAN DIEGO, Aug. 27, 2019 -- Anyone who has gone through the stress and discomfort of raw, irritated skin knows the relief that comes with slathering on a creamy lotion. Topical creams generally contain a few standard ingredients, but manufacturers know little about how these components interact to influence the performance of the product. Now, researchers report the first direct glimpse of how a cream or lotion is structured on the molecular scale, and it's not quite what they expected.

The researchers will present their results today at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"The long-term stability and clinical properties of a cream are determined by its fundamental structure," says Delaram Ahmadi, the graduate student who performed the study. "If we can understand the chemical microstructure of the cream and relate that to the structure of the skin, then perhaps we can better repair the compromised skin barrier."

One of Ahmadi's research advisors, David Barlow, Ph.D., adds, "We wanted to improve the science around cream formulation so that companies could more rationally formulate them to get exactly what they want. The most significant thing we found is that the textbook picture of the structure of a cream is very naïve."

Formulators have mostly inferred the structure of these emulsions based on indirect measurements, Barlow explains. But his group took a direct approach, with Ahmadi analyzing the cream using X-ray and neutron scattering techniques to determine how the ingredients were dispersed. Ahmadi and Barlow are at King's College London, and their co-investigator, Jayne Lawrence, Ph.D., is at Manchester University.

Cream is usually thought of as stacks of lamellae, or membranes, composed of surfactants and co-surfactants that maintain oil droplets dispersed within water (or vice versa). To reveal a cream's true structure, the researchers started with an aqueous cream formulation from the British Pharmacopoeia that contains two co-surfactants and a sodium dodecyl sulfate (SDS) surfactant. They also incorporated a diol known to act as a preservative. One by one, Ahmadi replaced each ingredient with heavier isotopic versions. The researchers then scattered X-rays and neutrons off the selectively isotope-labelled samples and, from the resulting patterns of scattering, determined the location of each ingredient and the aggregate it formed within the cream.

The results were surprising. Although they observed co-surfactants in the lamellar layers as predicted, the surfactant was not there. "The surfactant peak profile suggested that the molecule formed micelles in the cream," Ahmadi says. In addition, the preservative was not found in the aqueous layer, where scientists have always presumed it would be. It was, in fact, residing in the lamellae. Preservatives have an antimicrobial effect, thereby prolonging shelf-life. Formulators had assumed that to be an effective antimicrobial, the preservative had to be dissolved in the water layer. So, Ahmadi says this finding could mean the creams are essentially self-preserving.

The team is currently performing computer experiments to model the behavior of the preservatives in a bilayer system like a cream to understand why they are in the membrane layer. And they want to better understand the structure of the surfactant micelles dispersed in the layers. "I don't think anybody else has considered that there would be these micelles in the system at all," Barlow says. "This is new, and we need to think about where they are in the structure and what they are doing."

They also want to study different creams. Ahmadi says the formula from the British Pharmacopoeia is pretty basic, with only five ingredients. In addition, personal care companies have phased out SDS as a surfactant, so the researchers plan to analyze variations without SDS in the future.

A press conference on this topic will be held Tuesday, Aug. 27, at 10:30 a.m. Pacific time in the San Diego Convention Center. Reporters may check-in at the press center, Room 14B, Mezzanine Level, or watch live on Youtube http://bit.ly/acs2019sandiego. To ask questions online, sign in with a Google account.

Credit: 
American Chemical Society

Peptide hydrogels could help heal traumatic brain injuries

image: Self-assembled peptide nanofibers, shown here, form a hydrogel that improves survival of cortical neurons after a traumatic brain injury in rats.

Image: 
Biplab Sarkar and Vivek Kumar

SAN DIEGO, Aug. 27, 2019 -- Traumatic brain injury (TBI) -- defined as a bump, blow or jolt to the head that disrupts normal brain function -- sent 2.5 million people in the U.S. to the emergency room in 2014, according to statistics from the U.S. Centers for Disease Control and Prevention. Today, researchers report a self-assembling peptide hydrogel that, when injected into the brains of rats with TBI, increased blood vessel regrowth and neuronal survival.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

"When we think about traumatic brain injuries, we think of soldiers and athletes," says Biplab Sarkar, Ph.D., who is presenting the work at the meeting. "But most TBIs actually happen when people fall or are involved in motor vehicle accidents. As the average age of the country continues to rise, the number of fall-related accidents in particular will also increase."

TBIs encompass two types of injuries. Primary injury results from the initial mechanical damage to neurons and other cells in the brain, as well as blood vessels. Secondary injuries, which can occur seconds after the TBI and last for years, include oxidative stress, inflammation and disruption of the blood-brain barrier. "The secondary injury creates this neurotoxic environment that can lead to long-term cognitive effects," Sarkar says. For example, TBI survivors can experience impaired motor control and an increased rate of depression, he says. Currently, there is no effective regenerative treatment for TBIs.

Sarkar and Vivek Kumar, Ph.D., the project's principal investigator, wanted to develop a therapy that could help treat secondary injuries. "We wanted to be able to regrow new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI," Sarkar says. "Also, we wanted to create an environment where neurons can be supported and even thrive."

The researchers, both at the New Jersey Institute of Technology, had previously developed peptides that can self-assemble into hydrogels when injected into rodents. By incorporating snippets of particular protein sequences into the peptides, the team can give them different functions. For example, Sarkar and Kumar previously developed angiogenic peptide hydrogels that grow new blood vessels when injected under the skin of mice.

To adapt their technology to the brain, Sarkar and Kumar modified the peptide sequences to make the material properties of the hydrogel more closely resemble those of brain tissue, which is softer than most other tissues of the body. They also attached a sequence from a neuroprotective protein called ependymin. The researchers tested the new peptide hydrogel in a rat model of TBI. When injected at the injury site, the peptides self-assembled into a hydrogel that acted as a neuroprotective niche to which neurons could attach.

A week after injecting the hydrogel, the team examined the rats' brains. They found that in the presence of the hydrogel, survival of the brain cells dramatically improved, resulting in about twice as many neurons at the injury site in treated rats than in control animals with brain injury. In addition, the researchers saw signs of new blood vessel formation. "We saw some indications that the rats in the treated group were more ambulatory than those in the control group, but we need to do more experiments to actually quantify that," Sarkar says.

According to Kumar, one of the next steps will be to study the behavior of the treated animals to assess their functional recovery from TBI. The researchers are also interested in treating rats with a combination of their previous angiogenic peptide and their new neurogenic version to see if this could enhance recovery. And finally, they plan to find out if the peptide hydrogels work for more diffuse brain injuries, such as concussions. "We've seen that we can inject these materials into a defined injury and get good tissue regeneration, but we're also collaborating with different groups to find out if it could help with the types of injuries we see in soldiers, veterans and even people working at construction sites who experience blast injuries," Kumar says.

Credit: 
American Chemical Society

Adolescents' fun seeking predicts both risk taking and prosocial behavior

Research shows that risk-taking behaviors, such as binge drinking, may increase throughout adolescence. At the same time, so can prosocial behaviors (behaviors that involve doing good to benefit others). A new longitudinal study from the Netherlands sought to determine if these behaviors are related and whether certain brain regions can predict them. The study found that the two behaviors may be related and that both behaviors may be motivated by teenagers' efforts to have fun.

The study was conducted by researchers at Leiden University and the University of North Carolina, Chapel Hill. It is published in Child Development, a journal of the Society for Research in Child Development.

"We sought to test the pathways that support adolescents' development of rebellious and helpful behaviors," explains Neeltje E. Blankenstein, a postdoctoral researcher at Leiden University, who was first author of the study. "Because adolescence is often associated with negative stereotypes, our findings provide a more nuanced view on adolescent development by focusing on the relation between risk taking and prosocial behavior."

Researchers examined 210 youth who were part of the Braintime study, longitudinal research conducted in the Netherlands in 2011, 2013, and 2015. The participants were ages 8 to 25 years at the start of the study, ages 10 to 27 when they were surveyed the second time, and ages 12 to 29 when they were surveyed the last time. Participants completed questionnaires each time they were surveyed, reporting on how often they engaged in rebellious and prosocial behaviors. They also reported on their tendency to seek out fun or rewarding activities, and their social skills--specifically, empathy and social perspective taking, which the authors define as the ability to understand others' viewpoints (e.g., understanding both sides when two peers disagree).

Each time they were surveyed, the participants had a magnetic resonance imaging scan to measure the maturation of two brain regions--the nucleus accumbens and the medial prefrontal cortex--to determine whether these areas, which are important for risk taking and prosocial behavior, predicted the behaviors. The final time they were surveyed, participants reported on their rebellious or risk-taking behaviors, such as getting drunk and smoking, and on their prosocial behaviors, such as helping and comforting others.

The researchers found that:

Rebelliousness increased from early adolescence to late adolescence before declining into adulthood, and prosocial behavior peaked in mid- to late-adolescence.

Rebellious behavior and prosocial behavior were positively related to one another, even when controlling for age--that is, the more risk-taking behavior an adolescent showed, the more likely he or she was to behave prosocially.

The study also found that:

More prosocial behavior was predicted by more empathy and greater long-term increases in perspective taking.

More risk-taking behavior was predicted by greater increases in what the authors termed fun seeking--the tendency to seek out fun and exciting activities.

At the same time, this fun-seeking trait also predicted more prosocial behavior, suggesting that fun seeking leads some adolescents to develop risk-taking behavior and others to develop prosocial behavior. This suggests that the same developmental processes may result in both types of behaviors, the authors note. Fun seeking also predicted a combination of high risk taking and high prosocial behavior, indicating that some adolescents are prosocial risk takers.

The study pointed to some evidence that faster adolescent brain development (i.e., faster maturity) of the medial prefrontal cortex predicted less rebellious behavior. Activation of this region has been found to relate to risk taking, and this study showed that faster long-term structural development of this region also predicts risk taking.

Among the study's limitations, the authors acknowledge, are that their questionnaires measured only behaviors of interest to the study and did not look at risk taking and prosocial behavior in the lab or in real life. They recommend that follow-up studies test a wider range of rebellious and helpful behaviors and include experiments in the lab. In addition, because the questionnaires relied on self-reports, the authors say they may be biased by social desirability, that is, by participants answering in ways they thought would make them look better.

"Our study suggests that fun seeking may be a trait that leads to diverse aspects of adolescent development, and that adolescence is a time of both vulnerabilities--seen in risk taking--and opportunities--seen in helping behaviors," according to Eva H. Telzer, associate professor of psychology and neuroscience at the University of North Carolina, Chapel Hill, who co-led the study. "It also suggests that risk taking may serve positive goals, for instance, when adolescents take risks to help others."

Credit: 
Society for Research in Child Development

Artificial intelligence could use EKG data to measure patient's overall health status

DALLAS, August 27, 2019 - In the near future, doctors may be able to apply artificial intelligence to electrocardiogram data in order to measure overall health status, according to new research published in Circulation: Arrhythmia and Electrophysiology, a journal of the American Heart Association.

An electrocardiogram, also known as an EKG or ECG, is a test used to measure the electrical activity of the heart. While it's known that a patient's sex and age could affect an EKG, researchers hypothesized that artificial intelligence could determine a patient's gender and estimate their 'physiologic age' -- a measure of overall body function and health status distinct from chronological age.

Using EKG data of almost 500,000 patients, a type of artificial intelligence known as a convolutional neural network was trained to find similarities among the input and output data. Once trained, the neural network was tested for accuracy on the data of an additional 275,000 patients by predicting the output when only given input data.

The neural network estimated a patient's chronological age as higher after experiencing adverse health situations such as heart attack, low ejection fraction and coronary artery disease, and lower age if they experienced few or no adverse events.

"While physicians already consider whether a patient 'appears [their] stated age' as part of their baseline physical examination, the ability to more objectively and consistently assess this may impact healthcare on multiple levels," said study author Suraj Kapa, M.D., assistant professor of medicine and director for Augmented and Virtual Reality Innovation at Mayo Clinic in Rochester, Minnesota.

"Being able to more accurately assess overall health status may help doctors determine which patients they should examine further to determine if there are asymptomatic or currently silent diseases that could benefit from early diagnosis and intervention. For people at large, an AI-enhanced electrocardiogram could better show there may be something going on such as a new health issue or comorbid condition that they were otherwise unaware of," continued Kapa.

Researchers discovered that the artificial intelligence was able to accurately determine a patient's gender 90% of the time and could determine the chronological age group of a patient with 72% accuracy.

"This evidence -- that we might be gleaning some sort of 'physiologic age' -- was certainly both surprising and exciting for its potential role in future outcomes research, and may foster a new area of science where we seek to better understand the biologic underpinnings of such a finding," Kapa said.

While the study was able to draw from a large sample size, all individuals in the study were patients, and EKGs were administered for another clinical indication. Future studies with an overtly healthy population are needed to revalidate the neural network's determination. Additionally, gender in the study was self-identified by patients and may not represent the sex of all individuals in the study.

Credit: 
American Heart Association

U of T researchers engineer antibodies that unlock body's regenerative potential

image: University of Toronto researchers Stephane Angers and Sachdev Sidhu have created antibodies that could one day stimulate tissue in the body to repair itself, as described in a study published online in eLife, an open-access journal.

Image: 
Steve Southon, Leslie Dan Faculty of Pharmacy, University of Toronto

Our body makes antibodies to fight infections. But the synthetic versions of these molecules could hold the key to stimulating the body's ability to regenerate.

The findings come from a decade-long collaboration between the teams of Sachdev Sidhu, a professor in the Donnelly Centre for Cellular and Biomolecular Research, and Stephane Angers, Associate Dean of Research in the Leslie Dan Faculty of Pharmacy, that have been creating synthetic antibodies for diverse applications.

Antibodies are increasingly being developed into drugs thanks to their ability to bind and affect the function of other proteins in cells. Because they are encoded by genes, antibodies can be created in the lab using genome and protein engineering technologies.

Now Sidhu and Angers' teams have created antibodies that could one day stimulate tissue in the body to repair itself, as described in a study published online in eLife, an open-access journal. A newly launched Toronto startup, AntlerA Therapeutics, will turn the antibodies into drug-like molecules for regenerative medicine.

The work was done in collaboration with the Toronto Recombinant Antibody Centre, co-founded by Sidhu in the Donnelly Centre, which has created a massive catalog of synthetic antibodies for research and drug discovery.

"We are developing new molecules that have never been seen before and whose potential for regenerative medicine is enormous," says Sidhu, also a professor in U of T's Department of Molecular Genetics and co-founder of AntlerA.

"By capitalizing on the momentum of stem cells research and regenerative medicine that already exists in Toronto, we are ideally situated to commercialize these molecules."

Both Sidhu and Angers are members of the recently launched Precision Medicine Initiative (PRiME) at U of T that seeks to accelerate treatments targeting the biological underpinnings of an individual's disease. The team recently obtained support from the Medicine by Design program to continue to develop FLAgs and extend the technology to other growth factors.

Engineering new molecules

The antibodies were engineered to mimic key growth factors, proteins called Wnt (pronounced as "wynt") that normally instruct stem cells-- cells that can turn into any cell type in the body -- to form tissue in the embryo. Wnt proteins also activate stem cells for tissue repair following injury in adults, while mistakes in Wnt signaling can lead to cancer.

Scientists have long sought to co-opt Wnt as a tool for activating tissue regeneration. But these efforts were stymied by the molecules' complicated chemistry -- Wnt proteins are attached to fat molecules, or lipids, which makes their isolation in active form difficult.

"People have been trying for decades to purify Wnt proteins and make drugs out of them," says Sidhu. "Drug development would require further engineering of Wnt proteins. But Wnt are difficult to purify, let alone engineer--therefore they unlikely become drugs."

The associated lipids also prevent Wnt proteins from dissolving in water, making them unsuitable as medicines because they cannot be injected.

That's why the researchers decided to design antibodies that behave like Wnts, by binding to and activating two classes of Wnt receptors, Frizzled and LRP5/6, on the surface of cells, but are also water soluble and therefore easier to work with.

Called FLAgs, for Frizzled and LRP5/6 Agonists, the antibodies can be designed to replicate any one of the hundreds possible Wnt-receptor combinations (humans have 19 different Wnt proteins that can activate 10 Frizzled and eight co-receptors including LRP5/6).

To generate FLAgs, Yuyong Tao, a postdoctoral fellow in Sidhu's lab, came up with a new molecular configuration that does not exist in nature. Whereas natural antibodies have two binding sites, allowing them to bind to two targets, FLAgs have four, which means that a single molecule can recognize multiple receptors at the same time and mimic how Wnt proteins act in the body.

Stimulating tissue self-repair

When added to cell culture, FLAgs were able to substitute for Wnt proteins-- a hard-to-source but necessary ingredient in culture medium--and stimulate the formation of stem cell-derived intestinal organoids, three-dimensional balls of tissue that resemble the small intestine.

"These 3D organoids hold great potential for research and drug discovery but to grow them you need a source of Wnt proteins to activate stem cells," says Angers, whose team presented the findings earlier this month at an eminent Gordon conference in the U.S. "Now we have a defined protein, which we can easily obtain in large amounts and which can support the growth of organoids from various tissues."

"This is going to be really important and transformative for a lot people in the field," he says.

Most strikingly, when injected into mice, the FLAgs were able to activate the gut stem cells, showing that the antibodies are stable and functional inside the body. The finding raises hopes that FLAgs could be used as treatment for irritable bowel disease and other ailments to regenerate the intestinal lining when it is damaged. Other FLAg variants show promising results in lung, liver and bone regeneration as well as having the potential for treating eye disease.

AntlerA has already attracted investment to develop FLAgs into cutting edge therapeutics and is actively working on treatments for vision loss and bowel diseases. The startup's name was inspired by FLAgs' geometrical shape which resembles the antlers of deer and moose which are the fastest regenerating organs in animals.

"The type of discovery we report in our study was possible with a convergence of expertise," says Angers, co-founder of AntlerA. "Thanks to the close collaboration and proximity between our labs, we were able to apply protein engineering to activate a critical stem cell signaling pathway with the ultimate goal to develop regenerative medicine promoting the repair of diverse tissues in the body."

Credit: 
University of Toronto - Leslie Dan Faculty of Pharmacy

A new signaling pathway for mTor-dependent cell growth

image: Left: Protein kinase N (PKN) is active and inhibits PI3KC2ß (green). Right: PKN is missing. This causes PI3KC2ß to change the localization in the cell and to become active.

Image: 
Alexander Wallroth, FMP

The activation of mTor complex 1 in the cell is central to many vital processes in the body such as cell growth and metabolism. Overactivity of this signalling pathway can result in diseases such as in diabetic insulin resistance and cancer. A team led by the scientist Volker Haucke (Leibniz - Forschungsinstitut für Molekulare Pharmakologie and Freie Universität Berlin) has now discovered how inactivation of a certain lipid kinase promotes mTor complex 1 activity, and may therefore constitute a new point of attack for the treatment of diabetes and cancer. The results have just been published in the renowned journal Nature Cell Biology.

The signaling pathways in somatic cells are highly complex and specific mechanisms can only be triggered if several "switches" are "flipped" in a fixed sequence. However, given the high number of substances and substance complexes involved in the cellular signal transmission, finding these "switches" and identifying their role is a real challenge. The question of how mTor complex 1 can be deactivated in the cell has also been long unresolved. Even so, FMP researchers were able to shed light on this "switch" as early as 2017: revealing that a certain lipid kinase (PI3KC2ß) acts as a natural brake for the mTor protein and ensures that the mTor complex 1 is switched off, for example, when certain hormonal signals such as insulin are absent.

Now, a team led by FMP researcher Alexander Wallroth from Volker Haucke's research group has been scrutinizing how this lipid kinase is regulated. Alexander Wallroth: "We manipulated the lipid kinase in various ways and looked at the effects these manipulations had on mTOR and activity on cell growth". This work has allowed the researchers to uncover a mechanism for inactivating the PI3KC2ß lipid kinase. Another kinase that plays a key role here is protein kinase N (PKN), which renders the PI3KC2ß lipid kinase inactive, thereby indirectly activating mTOR in the process. Protein kinase N is regulated by growth factors that stimulate the mTor complex 2 at the cell membrane - the second protein complex in which mTor is present in the cell. This, in turn, activates PKN, which ultimately inactivates the lipid kinase.

"In doing so, we revealed two further components prone to pharmacological attack", explains Alexander Wallroth. Successfully inhibiting PKN activates the lipid kinase PI3KC2ß and ends up inhibiting mTOR-dependent cell growth. Conversely, if the signaling pathway is activated by growth factors, mTOR complex 2, and, finally, PKN, the lipid kinase remains inactive and the mTOR complex 1 is able to drive cell growth. Although inhibitors capable of inhibiting PKN have already been identified, their lack of specificity and tendency to block many other vital cellular processes currently precludes their use in living tissue.

"The most fascinating finding was the discovery of a cell biological signaling pathway that links mTor complexes 1 and 2, for example switching off 2 also impacts on 1," says Alexander Wallroth. In their previous work, the researchers were able to show that the lipid kinase PI3KC2ß, when activated, acts directly on mTor complex 1. Similarly, if PKN is activated by mTor complex 2, thereby inactivating the lipid kinase, the activity of mTor complex 1 is also affected. Up to now, little was known about mTor complex 2 compared to complex 1. The new results show that mTor complex 2 has a decisive impact on the activity of the important complex 1. "This paves the way for further and more detailed research into medical intervention to encompass various diseases such as insulin resistance or cancer," emphasizes Alexander Wallroth.

Credit: 
Forschungsverbund Berlin

High fat diet during pregnancy slows learning in offspring, rat study suggests

image: Tamashiro and Cordner

Image: 
Johns Hopkins Medicine

In a bid to further explore how a mother-to-be's diet might affect her offspring's brain health, Johns Hopkins Medicine researchers have found that pregnant and nursing rats fed high fat diets have offspring that grow up to be slower than expected learners and that have persistently abnormal levels of the components needed for healthy brain development and metabolism.

In the experiments, pregnant rats were allowed to overeat repeatedly a diet similar in fat to that of typical fast food meals that people eat. Although the study was performed on animals, the researchers say their findings -- described in the August issue of Experimental Neurology -- likely apply in some measure to other mammals including humans, and they add to evidence that unhealthy diets may damage a fetus's developing brain in specific ways.

Because so much of mammalian brain biology and metabolism is similar, the research "may well hold warnings for people that high fat diets during pregnancy are a concern," says Kellie Tamashiro, Ph.D., M.S., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "Pregnant moms who may not have access to fresh foods or healthy diets may have their unborn children's brain development suffer, and there's an opportunity to intervene to change their offspring's learning trajectory to a better one."

Tamashiro's laboratory studies how, during pregnancy, stress, diet and the immune system can contribute to neuropsychiatric and metabolic diseases such as diabetes. During the current study, which focused on the impact of a high fat diet on the developing brain, they fed pregnant rats a diet of 60% calories from fat in their food pellets throughout pregnancy and until their pups were finished weaning -- a period of three weeks. The typical American and Western European diet has about 45% calories from fat. The researchers compared the rats' high fat food to a fast food diet.

"The pregnant rats had free access to a very high fat diet where they were eating as much as they wanted and they did overeat, just like we do in Western society," says Zachary Cordner, M.D., Ph.D., chief resident of psychiatry at The Johns Hopkins Hospital and the study's lead author.

When the offspring were finished weaning, at about 21 days after birth, they were fed for the next three months a normal rat chow diet in which 20% of the calories came from fat. At about 4 months of age, the adult rats were evaluated for their learning and memory abilities using a maze that consisted of a round platform with 20 holes around the perimeter, only one of which led to an exit.

The researchers note that rats don't like wide-open spaces, because such an environment exposes them to predators in the wild, so they would instinctively seek to exit the open platform. Normal rats consistently take three to four tries to learn where the maze exit is, but rats from mothers fed the high fat diets took up to nine times to learn the location.

A week after learning the exit location, the rats were tested again. Those born to mothers on a normal diet remembered the maze and only took about five seconds to find the exit, but the rats whose mothers had a high fat diet took about 20 seconds on average.

In a second set of experiments, the team exploited the fact that normally, rats are curious and like to check out new objects in their environment. When they familiarized rats with Lego blocks and then swapped one of the known blocks with a different one the next day, the rats typically spent more time exploring the new one. But rats from mothers who were fed the high fat diets spent just as much time around the familiar object as they did the new one, suggesting they didn't recognize the object as new.

"The rats from moms fed high fat diets were slow learners," says Cordner. "They were able to learn as well as the normal rats, but it took them longer to do it."

To figure out what might have accounted for the slow learning, the researchers compared the levels of products made by genes in the brains of normal rats with the levels in rats whose mothers were fed high fat diets during pregnancy and nursing. They focused on the part of the brain that is vital to learning and memory just when the pups were finished weaning and a few months later when the rats were adults.

The rats from pregnant mothers that were fed high fat diets had lower levels of insulin receptors, leptin receptors and glucose transporter 1 than did rats that came from mothers fed normal diets.

Insulin helps regulate blood sugar. In rats and all mammals, the insulin receptor detects insulin and initiates the process to help get sugar out of the blood -- using the glucose transporter -- and into the body's cells for energy. Leptin is a hormone that suppresses hunger, and it binds to the leptin receptor to regulate body weight and metabolism.

"The roles of genes involved in energy metabolism affect learning and memory too, and this role changes over time," says Cordner. "Initially, these genes are involved in the formation of the fetal brain, and later on in life they are involved in learning and memory, in addition to energy metabolism.

"Our findings build on what we already know about the role of these hormones and nutrients on brain health, and clearly support the idea that a high fat diet does impact neuropsychiatric risk that carries over into adulthood, most likely by interfering with how genes are regulated and expressed," adds Cordner.

Credit: 
Johns Hopkins Medicine