Routine eye scans may give clues to cognitive decline in diabetes

As they age, people with diabetes are more likely to develop Alzheimer’s disease and other cognitive disorders than are people without diabetes. Scientists at Joslin Diabetes Center now have shown that routine eye imaging can identify changes in the retina that may be associated with cognitive disorders in older people with type 1 diabetes.

These results may open up a relatively easy method for early detection of cognitive decline in this population, providing better ways to understand, diagnose and ultimately treat the decline, said George L. King, MD, Joslin’s Chief Scientific Officer and senior author on a paper about the study in the Journal of Clinical Endocrinology & Metabolism.

Previous research had demonstrated an association between proliferative diabetic retinopathy (PDR, a complication of diabetes that can severely damage eyesight) and cognitive impairment in people with type 1 diabetes. “Since we knew that there were cellular changes in the retina that might reflect changes in the brain, we were interested to see whether imaging techniques that visualize those changes in the retina might be reflective of changes in cognitive functions,” said Ward Fickweiler, MD, a Joslin postdoctoral fellow and first author on the paper.

The scientists drew on eye scans routinely gathered from patients as part of normal vision care at Joslin’s Beetham Eye Institute. One set of scans was based on optical coherence tomography (OCT, a technique employing light to provide cross-sections of the retina). A second set of scans employed OCT angiography (OCTA, an extension of OCT technology that examines blood vessels in the retina). Both types of scans are non-invasive and widely available in eye clinics in the United States, and can be performed within minutes.

The study enlisted 129 participants in the Joslin Medalist Study, which examines outcomes among people who have had type 1 diabetes for 50 years or longer. These volunteers took a series of cognitive tests that included tasks probing memory function as well as psychomotor speed (assessing the time it took to arrange objects by hand).

Strikingly, the researchers found very strong associations between performance on memory tasks and structural changes in deep blood vessel networks in the retina. “Memory is the main cognitive task that is affected in Alzheimer’s disease and cognitive decline, so that was exciting,” Fickweiler said.

The Joslin team also discovered strong associations between PDR and psychomotor speed. This finding reinforced earlier outcomes that had been identified among a smaller group of Joslin Medalists, and provided details about related changes in retinal structure. Additionally, the researchers saw that PDR was associated with memory performance among the larger group of Medalists.

While these results need to be confirmed in larger clinical investigations, the routine eye exams do seem to detect the cognitive changes happening in people with diabetes, said Fickweiler.

Currently, other ways to detect conditions such as Alzheimer’s disease such as MRI scans are difficult and expensive. People typically are tested only when they’re showing symptoms of cognitive decline and treatments at that stage generally don’t offer much help.

“If you can detect the condition at an earlier stage, when they’re still asymptomatic, that may benefit patients,” Fickweiler said. Earlier detection also could aid the quest to develop better therapies for neurocognitive diseases.

The Joslin team plans to launch a larger prospective study to confirm the potential of eye imaging to pick up signs of cognitive decline over time. This research will include people with type 1 diabetes who are younger and haven’t had the disease for as long as the Medalists. The scientists also will analyze MRI brain images and postmortem brain samples donated by Medalists.

Additionally, the investigators will look for common mechanisms that may inflict damage on brain and retina tissues, which share much of their early embryonic development pathways. Likely suspects in people with diabetes include impaired blood vessels and high or low levels of blood glucose. The autoimmunity that drives type 1 diabetes also might inflict other forms of harm, King said.

Notably, Joslin Medalists often display relatively low levels of the complications that can afflict those with long-term type 1 diabetes. For instance, almost half of Medalists don’t develop advanced eye disease, and only one of the 129 Medalists in the eye-scan study may have Alzheimer’s disease. “It is possible that in the Medalists, a shared mechanism alters the progression of the early stages of retinal and brain neurodegeneration, and provides protection against both PDR and Alzheimer’s disease,” Fickweiler speculated.

In addition to follow-up work in type 1 diabetes, King and his team plan to perform a similar study for people with type 2 diabetes. PDR also is associated with cognitive decline in this much larger group of patients, who also get OCT and OCTA eye scans as part of their regular vision care.

The paper’s co-authors include Joslin’s Emily Wolfson, Samantha Paniagua, Atif Adam, Vanessa Bahnam, Konstantina Sampani, I-Hsien Wu, Gail Musen, Lloyd Aiello, Hetal Shah and Jennifer Sun. Marc Yu of Harvard Medical School also contributed.

Funding came from the Dianne Nunnally Hoppes Fund; the Beatson Pledge Fund; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Eye Institute; the National Institutes of Health; JDRF; and the American Diabetes Association.

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Reawakened geyser does not foretell Yellowstone volcanic eruptions

When Yellowstone National Park’s Steamboat Geyser — which shoots water higher than any active geyser in the world — reawakened in 2018 after three and a half years of dormancy, some speculated that it was a harbinger of possible explosive volcanic eruptions within the surrounding geyser basin. These so-called hydrothermal explosions can hurl mud, sand and rocks into the air and release hot steam, endangering lives; such an explosion on White Island in New Zealand in December 2019 killed 22 people.

A new study by geoscientists who study geysers throws cold water on that idea, finding few indications of underground magma movement that would be a prerequisite to an eruption. The geysers sit just outside the nation’s largest and most dynamic volcanic caldera, but no major eruptions have occurred in the past 70,000 years.

“Hydrothermal explosions — basically hot water exploding because it comes into contact with hot rock — are one of the biggest hazards in Yellowstone,” said Michael Manga, professor of earth and planetary sciences at the University of California, Berkeley, and the study’s senior author. “The reason that they are problematic is that they are very hard to predict; it is not clear if there are any precursors that would allow you to provide warning.”

He and his team found that, while the ground around the geyser rose and seismicity increased somewhat before the geyser reactivated and the area currently is radiating slightly more heat into the atmosphere, no other dormant geysers in the basin have restarted, and the temperature of the groundwater propelling Steamboat’s eruptions has not increased. Also, no sequence of Steamboat eruptions other than the one that started in 2018 occurred after periods of high seismic activity.

“We don’t find any evidence that there is a big eruption coming. I think that is an important takeaway,” he said.

The study will be published this week in Proceedings of the National Academy of Sciences.

Manga, who has studied geysers around the world and created some in his own laboratory, set out with his colleagues to answer three main questions about Steamboat Geyser: Why did it reawaken? Why is its period so variable, ranging from 3 to 17 days? and Why does it spurt so high?

The team found answers to two of those questions. By comparing the column heights of 11 different geysers in the United States, Russia, Iceland and Chile with the estimated depth of the reservoir of water from which their eruptions come, they found that the deeper the reservoir, the higher the eruption jet. Steamboat Geyser, with a reservoir about 25 meters (82 feet) below ground, has the highest column — up to 115 meters, or 377 feet — while two geysers that Manga measured in Chile were among the lowest — eruptions about a meter (3 feet) high from reservoirs 2 and 5 meters below ground.

“What you are really doing is you are filling a container, it reaches a critical point, you empty it and then you run out of fluid that can erupt until it refills again,” he said. “The deeper you go, the higher the pressure. The higher the pressure, the higher the boiling temperature. And the hotter the water is, the more energy it has and the higher the geyser.”

To explore the reasons for Steamboat Geyser’s variability, the team assembled records related to 109 eruptions going back to its reactivation in 2018. The records included weather and stream flow data, seismometer and ground deformation readings, and observations by geyser enthusiasts. They also looked at previous active and dormant periods of Steamboat and nine other Yellowstone geysers, and ground surface thermal emission data from the Norris Geyser Basin.

They concluded that variations in rainfall and snow melt were probably responsible for part of the variable period, and possibly for the variable period of other geysers as well. In the spring and early summer, with melting snow and rain, the underground water pressure pushes more water into the underground reservoir, providing more hot water to erupt more frequently. During winter, with less water, lower groundwater pressure refills the reservoir more slowly, leading to longer periods between eruptions. Because the water pushed into the reservoir comes from places even deeper than the reservoir, the water is decades or centuries old before it erupts back to the surface, he said.

In October, Manga’s team members demonstrated the extreme impact water shortages and drought can have on geysers. They showed that Yellowstone’s iconic Old Faithful Geyser stopped erupting entirely for about 100 years in the 13th and 14th centuries, based on radiocarbon dating of mineralized lodgepole pine trees that grew around the geyser during its dormancy. Normally the water is too alkaline and the temperature too high for trees to grow near active geysers. The dormancy period coincided with a lengthy warm, dry spell across the Western U.S. called the Medieval Climate Anomaly, which may have caused the disappearance of several Native American civilizations in the West.

“Climate change is going to affect geysers in the future,” Manga said.

Manga and his team were unable to determine why Steamboat Geyser started up again on March 15, 2018, after three years and 193 days of inactivity, though the geyser is known for being far more variable than Old Faithful, which usually goes off about every 90 minutes. They could find no definitive evidence that new magma rising below the geyser caused its reactivation.

The reactivation may have to do with changes in the internal plumbing, he said. Geysers seem to require three ingredients: heat, water and rocks made of silica — silicon dioxide. Because the hot water in geysers continually dissolves and redeposits silica — every time Steamboat Geyser erupts, it brings up about 200 kilograms, or 440 pounds of dissolved silica. Some of this silica is deposited underground and may change the plumbing system underneath the geyser. Such changes could temporarily halt or reactivate eruptions if the pipe gets rerouted, he said.

Manga has experimented with geysers in his lab to understand why they erupt periodically, and at least in the lab, it appears to be caused by loops or side chambers in the pipe that trap bubbles of steam that slowly dribble out, heating the water column above until all the water can boil from the top down, explosively erupting in a column of water and steam.

Studies of water eruptions from geysers could give insight into the eruptions of hot rock from volcanoes, he said.

“What we asked are very simple questions and it is a little bit embarrassing that we can’t answer them, because it means there are fundamental processes on Earth that we don’t quite understand,” Manga said. “One of the reasons we argue we need to study geysers is that if we can’t understand and explain how a geyser erupts, our hope for doing the same thing for magma is much lower.”

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Scientists develop new approach to understanding massive volcanic eruptions

A geosciences team led by the University of South Florida (USF) has developed a new way to reconstruct the sizes of volcanic eruptions that occurred thousands of years ago, creating a first-of-its kind tool that can aid scientists in understanding past explosive eruptions that shaped the earth and improve the way of estimating hazards of future eruptions.

The advanced numerical model the USF team developed allows scientists to reconstruct eruption rates through time by estimating the dimensions of the umbrella clouds that contribute to the accumulation of vast deposits of volcanic ash. The research is published in the new edition of the Nature Journal, Communications, Earth and Environment.

The research, which was used to decipher the 2,500-year-old eruption of a volcano in Ecuador, was led by USF doctoral candidate Robert Constantinescu in collaboration with USF colleagues Research Associate Laura Connor, Professor Chuck Connor, Associate Professor Sylvain Charbonnier, doctoral alum Alain Volentik and other members of an international team. USF’s Volcanology Group is one of the world’s leading centers of volcano science and hazard assessment.

When large explosive eruptions occur, they form laterally spreading umbrella clouds into the stratosphere, facilitating the transport of fine-grained ash over hundreds of miles that settles and covers large swaths of land.

Current technology allows scientists to observe ash clouds. However, past eruptions are characterized based on the geological interpretation of their tephra deposits — the pieces and fragments of rock ejected into the air by an erupting volcano. By estimating the erupted volume and mass, plume height, umbrella cloud dimensions and other characteristics, the scientists are able to understand and characterize the volcanic eruptions, therefore improving the forecast of future events.

Using a series of field techniques combined with statistical and numerical modeling, volcanologists extract information from the deposits in order to characterize and classify an eruption on one of the most commonly used scales, the Volcanic Explosivity Index (VEI). Until now, the most sought-after information is the eruption column height and the total erupted mass or volume, Constantinescu said.

But over time, deposits erode and can provide an uncertain picture of older eruptions. Also, current models have been limited in that they assume all volcanic eruptions created mostly vertical plumes, Constantinescu said, and don’t account for large explosive eruptions that form laterally spreading umbrella ash clouds.

The USF team’s work shows that it is the dimensions of the umbrella clouds that is the telling factor in reconstructing past large explosive eruptions.

“The better we can reconstruct the nature of past eruptions from deposit data, the better we can anticipate potential hazards associated with future explosive eruptions,” the team wrote in the new journal article.

The researchers propose updating the VEI scale with the umbrella cloud dimensions, which can now be easily estimated using the mathematical models they’ve developed.

The researchers applied their model to the tephra deposit of the eruption of Pululagua, a now dormant volcano about 50 miles north of the capital city of Quito. Ecuador is considered one of the world’s most hazardous countries for volcanoes. The volcano last erupted an estimated 2,500 years ago and the area is now a geobotanical reserve renowned for its biodiversity and lush green landscape.

There are about 1,500 potentially active volcanoes worldwide, in addition to those that lurk beneath the world’s oceans. In 2020, there were at least 67 confirmed eruptions from 63 different volcanoes, according to the Smithsonian Institution Global Volcanism Program. “If in modern times the umbrella clouds of large eruptions are easily observed, we now have the ability to estimate the umbrella clouds of past eruptions,” Constantinescu said. “Our numerical model enables us to better characterize past volcanic eruptions and inform models for future hazard assessment.”

The USF team was joined in the research by Aurelian Hopulele-Gligor of Cluj-Napoca, Romania; Costanza Bonadonna of the University of Geneva; and Jan M. Lindsay of the University of Auckland. The research was funded in part by the National Science Foundation.

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Uncovering how plants see blue light

Plants can perceive and react to light across a wide spectrum. New research from Prof. Nitzan Shabek’s laboratory in the Department of Plant Biology, College of Biological Sciences shows how plants can respond to blue light in particular.

“Plants can see much better than we can,” Shabek said.

Plants don’t have dedicated light-detecting organs, like our eyes. They do have a variety of dedicated receptors that can sense almost every single wavelength. One such are the blue light photoreceptors called cryptochromes. When the cryptochrome detects an incoming photon, it reacts in a way that triggers a unique physiological response.

Cryptochromes probably appeared billions of years ago with the first living bacteria and they are very similar across bacteria, plants and animals. We have cryptochromes in our own eyes, where they are involved in maintaining our circadian clock. In plants, cryptochromes govern a variety of critical processes including seed germination, flowering time and entrainment of the circadian clock. However, the photochemistry, regulation, and light-induced structural changes remain unclear.

In a new study, published Jan. 4 in Nature Communications Biology, Shabek’s lab determined the crystal structure of part of the blue-light receptor, cryptochrome-2, in the model plant Arabidopsis thaliana. They found that the light-detecting part of the molecule changes its structure when it reacts with light particles, going from a single unit to a structure made of four units linked together, or tetramer.

Rearrangement leads to gene activation

“This rearrangement process, called photo-induced oligomerization, is also very intriguing because certain elements within the protein undergo changes when exposed to blue light. Our molecular structure suggests that these light-induced changes release transcriptional regulators that control expression of specific genes in plants,” Shabek said.

The researchers were able to work out the structure of cryptochrome-2 with the aid of the Advanced Light Source X-ray facility at the Lawrence Berkeley National Laboratory.

The Shabek lab broadly studies how plants sense their environment from the molecular to the organismal levels.

“This work is part of our long-term goals to understand sensing mechanisms in plants. We are interested in hormone perceptions as well as light signaling pathways,” Shabek said.

The team first solved the crystal structure of the blue light receptor two years ago, using X-ray crystallography and biochemical approaches. With recent advances in plant sciences and structural biology, they were able to update the model and reveal the missing piece of the puzzle.

Story Source:

Materials provided by University of California – Davis. Original written by Andy Fell. Note: Content may be edited for style and length.

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