The study, performed on mice induced with a model of MS and the first to investigate IndCl’s effect on the pathology and function of the complete afferent visual pathway, is published in Brain Pathology. The afferent visual pathway includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

In MS, a disease in which the immune system “demyelinates” or eats away at the protective covering of nerves, the initial period of inflammation and demyelination often damages the optic nerve and other parts of the visual system first. As a result, approximately 50% of patients with MS experience optic neuritis — inflammatory demyelination of the optic nerve — prior to showing initial symptoms. Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.

The optic nerve, a heavily myelinated bundle of nerves located at the back of the eye, transfers visual information from the retina to the vision centers of the brain through electrical impulses. Myelin acts as an insulating substance that speeds the transmission of these electrical impulses. Partial myelin loss slows transmission of visual information; severe myelin loss may stop the signal altogether.

The researchers used IndCl to assess its impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.

“IndCl has been previously shown in mice to reduce motor disability, increase myelination, and neuroprotection in the spinal cord and corpus callosum,” said Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study’s lead author. “Its effects in the visual system, however, were not evaluated until now. Our study shows the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, are able to restore some function with IndCl treatment with successful attenuation in inflammation and an increase in remyelination.”

The visual pathway in mice is similar to that in humans. The mouse brain is, therefore, an excellent model for scientists to study vision impairment. In the lab, Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice. At the end of the experiment, they performed functional assay to measure the visual electrical signal; and immunohistochemistry to examine the visual pathway. The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.

For Tiwari-Woodruff, the next question is how IndCl treatment induces functional remyelination in the visual pathway. Her lab, in collaboration with the lab of co-author John A. Katzenellenbogen at the University of Illinois at Urbana-Champaign, is investigating new drugs that are analogues of IndCl.

“Measuring visual function and recovery in the presence of novel therapies can be used to screen more effective therapies that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage,” Tiwari-Woodruff said.

Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.

“We treated the MS mice with IndCl at peak disease,” Tiwari-Woodruff said. “If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There’s a point of no return. Our paper stresses that to acquire vision improvement, treatment must start early. Early treatment can recover 75%-80% of the original function.”

Tiwari-Woodruff stressed that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.

“There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS,” Tiwari-Woodruff said. “Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good estrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment.”

The counterintuitive finding highlights the influence of airborne particles, or aerosols, that block incoming sunlight. When emissions of aerosols dropped last spring, more of the Sun’s warmth reached the planet, especially in heavily industrialized nations, such as the United States and Russia, that normally pump high amounts of aerosols into the atmosphere.

“There was a big decline in emissions from the most polluting industries, and that had immediate, short-term effects on temperatures,” said NCAR scientist Andrew Gettelman, the study’s lead author. “Pollution cools the planet, so it makes sense that pollution reductions would warm the planet.”

Temperatures over parts of Earth’s land surface last spring were about 0.2-0.5 degrees Fahrenheit (0.1-0.3 degrees Celsius) warmer than would have been expected with prevailing weather conditions, the study found. The effect was most pronounced in regions that normally are associated with substantial emissions of aerosols, with the warming reaching about 0.7 degrees F (0.37 C) over much of the United States and Russia.

The new study highlights the complex and often conflicting influences of different types of emissions from power plants, motor vehicles, industrial facilities, and other sources. While aerosols tend to brighten clouds and reflect heat from the Sun back into space, carbon dioxide and other greenhouse gases have the opposite effect, trapping heat near the planet’s surface and elevating temperatures.

Despite the short-term warming effects, Gettelman emphasized that the long-term impact of the pandemic may be to slightly slow climate change because of reduced emissions of carbon dioxide, which lingers in the atmosphere for decades and has a more gradual influence on climate. In contrast, aerosols — the focus of the new study — have a more immediate impact that fades away within a few years.

The study was published in Geophysical Research Letters. It was funded in part by the National Science Foundation, NCAR’s sponsor. In addition to NCAR scientists, the study was co-authored by scientists at Oxford University, Imperial College, and the University of Leeds.

Teasing out the impacts

Although scientists have long been able to quantify the warming impacts of carbon dioxide, the climatic influence of various types of aerosols — including sulfates, nitrates, black carbon, and dust — has been more difficult to pin down. One of the major challenges for projecting the extent of future climate change is estimating the extent to which society will continue to emit aerosols in the future and the influence of the different types of aerosols on clouds and temperature.

To conduct the research, Gettelman and his co-authors used two of the world’s leading climate models: the NCAR-based Community Earth System Model and a model known as ECHAM-HAMMOZ, which was developed by a consortium of European nations. They ran simulations on both models, adjusting emissions of aerosols and incorporating actual meteorological conditions in 2020, such as winds.

This approach enabled them to identify the impact of reduced emissions on temperature changes that were too small to tease out in actual observations, where they could be obscured by the variability in atmospheric conditions.

The results showed that the warming effect was strongest in the mid and upper latitudes of the Northern Hemisphere. The effect was mixed in the tropics and comparatively minor in much of the Southern Hemisphere, where aerosol emissions are not as pervasive.

Gettelman said the study will help scientists better understand the influence of various types of aerosols in different atmospheric conditions, helping to inform efforts to minimize climate change. Although the research illustrates how aerosols counter the warming influence of greenhouse gases, he emphasized that emitting more of them into the lower atmosphere is not a viable strategy for slowing climate change.

“Aerosol emissions have major health ramifications,” he said. “Saying we should pollute is not practical.”

Single-celled organisms in the open ocean use a diverse array of genetic tools to detect light, even in tiny amounts, and respond, according to a study published Feb. 1 in the Proceedings of the National Academy of Sciences.

“If you look in the ocean environment, all these different organisms have this day-night cycle. They are very in tune with each other, even as they get moved around. How do they know when it’s day? How do they know when it’s night?” said lead author Sacha Coesel, a research scientist in oceanography at the UW.

Though invisible to the human eye, ocean microbes support all marine life, from sardines to whales. Knowing these communities’ inner workings could reveal how they will fare under changing ocean conditions.

“Just like rainforests generate oxygen and take up carbon dioxide, ocean organisms do the same thing in the world’s oceans. People probably don’t realize this, but these unicellular organisms are about as important as rainforests for our planet’s functioning,” Coesel said.

By analyzing RNA filtered out of seawater samples collected throughout the day and night, the study identifies four main groups of photoreceptors, many of them new. This genetic activity uses light to trigger changes in the metabolism, growth, cell division, movements and death of marine organisms.

The discovery of these new genetic “light switches” could also aid in the field of optogenetics, in which a cell’s function can be controlled with light exposure. Today’s optogenetic tools are engineered by humans, but versions from nature might be more sensitive or better detect light of particular wavelengths, the researchers said.

“This work dramatically expanded the number of photoreceptors — the different kinds of those on-off switches — that we know of,” said senior author Virginia Armbrust, a UW professor of oceanography.

Not surprisingly, many of the new tools were for light in the blue range, since water filters out red wavelengths (which is why oceans appear blue). Some were also for green light, Coesel said.

The researchers collected water samples far from shore and looked at all genetic activity from protists: single-celled organisms with a nucleus. They filtered the water to select organisms measuring between 200 nanometers to one-tenth of a millimeter across. These included photosynthetic organisms, like algae, which absorb light for energy, as well as other single-celled plankton that gain energy by consuming other organisms.

The team collected samples every four hours, day and night, for four days in the North Pacific near Hawaii. Researchers used trackers to follow the currents about 50 feet (15 meters) below the surface so that the samples came from the same water mass.

The study also looked at samples that came from a depth of 120 and 150 meters (400 and 500 feet), in the ocean’s “twilight zone.” Even there, the genetic activity showed that the organisms were responding to very low levels of sunlight.

While the sun is up, these organisms gain energy and grow in size, and at night, when the ultraviolet light is less damaging to their DNA, they undergo cell division.

“Daylight is important for ocean organisms, we know that, we take it for granted. But to see the rhythm of genetic activity during these four days, and the beautiful synchronicity, you realize just how powerful light is,” Armbrust said.

Future work will look at places farther from the equator, where plankton communities are more subjected to the changing seasons.

“2019 had just a horrendous monsoon,” Carroll said. “Just the weakest monsoon. And we’d had a few years of weak monsoons before that, which had really gotten me wondering, how important is the monsoon to late summer streamflow here in the Upper Colorado River basin? And how do monsoons influence the following year’s streamflow?”

Working in partnership with colleagues David Gochis, Ph.D., of the National Center for Atmospheric Research and Kenneth Williams, Ph.D., of Lawrence Berkeley National Laboratory, Carroll set out to explore the importance of monsoon rain in streamflow generation in a Colorado River headwater basin.

The team’s findings, which are published in a new paper in Geophysical Research Letters, point to both the importance of monsoon rains in maintaining the Upper Colorado River’s water supply and the diminishing ability of monsoons to replenish summer streamflow in a warmer future with less snow accumulation.

Their study focuses on the East River watershed, a pristine, high elevation, snow-dominated headwater basin of the Colorado River and part of the Watershed Function Scientific Focus Area (SFA) program that is exploring how disturbances in mountain systems — like floods, drought, changing snowpack and earlier snowmelt -impact the downstream delivery of water, nutrients, carbon, and metals.

Using a hydrologic model and multiple decades of climate data from the East River watershed, Carroll and her colleagues found that monsoon rains normally deliver about 18 percent of the basin’s water and produce about 10 percent of the annual streamflow, with streamflow generated primarily in the higher elevations of the basin.

“The amount of streamflow produced by monsoons, while not geographically extensive, is actually somewhat substantial,” Carroll said. “It was larger than I thought it would be. That doesn’t mean all of that water gets to a reservoir -some likely is used by riparian vegetation or irrigation, but it still does go to meet some need within the basin.”

Next, the team explored the ability of these summer rains to produce streamflow during cool years with high snow accumulation, and during warm years with less snow accumulation. During cool years with more snow, soil moisture levels were higher going into summer, and greater streamflow was generated by the monsoon rains. During warmer years with low snowpack, dry soils absorbed much of the monsoonal rains, and less runoff made it to the streams.

“You can think of the soil zone as a sponge that needs to fill up before it can allow water to move through it,” Carroll said. “So, if it’s already depleted because you had low snowpack, the monsoon then has to fill it back up, and that decreases the amount of water you actually get in the river.”

As the climate warms, snowpack in the Rocky Mountains and other mountain systems is expected to decline, leading to reduced streamflow. Rising temperatures also lead to increased soil evaporation and increased water use by plants. According to the results of Carroll’s study, these changes will reduce the ability of water from the monsoon to make it to the river as streamflow.

“Our results indicate that as we move toward a climate that is warmer and our snowpack decreases, the ability of monsoon rain to buffer these losses in streamflow is also going to go down,” Carroll said. “So, the monsoon is not some silver bullet that is going to help mitigate those changes.”

The Colorado River is a critically important resource for people living in Southern Nevada, where it accounts for about 90 percent of the water supply. Although runoff from winter snowpack provides a much larger proportion of streamflow each year than the monsoons, the monsoonal moisture is important to both ecosystems and people in part because it arrives at a different time of year. And in a system like the Colorado River, where every drop of water is allocated, if monsoon rains do not arrive, it creates a shortage somewhere downstream.

“In terms of water resources, if monsoon rains are useful and contribute to late-season streamflow, then the loss of that water obviously has implications for the ecology of these systems,” Carroll said. “This water is really important in supporting aquatic habitat there. But it’s also really important for human use. If any amount of water that we rely on isn’t there, then something has to give. The Upper Basin will have to consider how they are going to manage their water to meet those downstream obligations.”

Bile acids are key players in digestion and overall gut health. Produced in the liver and released after we eat, these acids not only break down cholesterol and help regulate fat absorption, they also have a huge impact on what types of bacteria colonize the gut.

As bile acids move through the gut, they are initially chemically modified through the addition of an amino acid (frequently glycine or taurine), creating a complex “conjugated” bile acid pool. Some gut bacteria have enzymes, called bile salt hydrolases (BSHs), which can cleave or “deconjugate” these amino acids from the bile acids, allowing other bacteria to further transform the bile acids as they continue through the colon. These transformations affect the bile acids’ toxicity, which in turn affects the ability of different bacteria to survive in the gut.

“The assumed relationship was that probiotic bacteria like Lactobacillus have BSHs that just deconjugate the bile acid, rendering it less toxic and allowing the bacteria to survive,” says Casey Theriot, associate professor of infectious disease at NC State and co-corresponding author of a paper describing the work. “But the reality is a lot more complex — these enzymes are more specific than we thought. Depending on which BSH is there and which bile acid it acts on, you can shape the gut in different ways, making it more or less hospitable to bacteria or pathogens.”

“The interplay between bile and bacteria has a huge impact on their ability to live, thrive or die in a very competitive environment,” says Rodolphe Barrangou, Todd R. Klaenhammer Distinguished Professor in Probiotics Research at NC State and co-corresponding author of the work. “So we set out to further investigate that relationship.”

Theriot, Barrangou, and Matthew Foley, a postdoctoral research scholar at NC State and first author of the paper, did both in vitro and in vivo experiments to determine how and whether BSHs reduced bile acid toxicity. First, they looked at the growth of two strains of Lactobacillus in the presence of different bile acids and were surprised to find that the conjugated glycine or taurine played a big role in determining the toxicity of a given bile acid. The BSHs were then isolated and biochemically studied to determine whether they were more or less active on specific bile salts, and whether they could affect the survival of lactobacilli when grown in the presence of bile acids.

They found that bile acid toxicity was not merely dependent upon whether the bile acid was conjugated or deconjugated by a BSH; rather, the relationships were dependent upon the type of bile acid, the bacteria being acted upon, and which BSH was present.

“When we altered the BSH composition of these Lactobacillus strains, their tolerance of the bile acids and thus their competitive fitness were also altered,” Barrangou says. “These BSH enzymes have diverse properties. Bacteria pick up and drop off enzymes regularly — sometimes they pick up enzymes that will help them survive (make bile acid less toxic) or they could pick up an enzyme that will hurt competition.

“So the relationship between bacteria, BSHs and bile acids aren’t just one to one. This knowledge could help us strategize ways to improve human health by extending the lifespan of beneficial microbes or preventing the colonization of pathogens.”

“If we’re going to try and design the gut microbiota in the future, we really have to understand all the players — bacteria, enzymes and bile acids — and their situational relationships.” Theriot says. “This work is a big first step in that direction.”

“BSHs are just one tool that lactobacilli use to adapt to life inside the competitive intestinal tract.” Foley says. “Our future work will further our knowledge of bacterial-modified bile and its consequences for our health.”

The work appears in Proceedings of the National Academy of Sciences, and was supported by the National Institutes of Health (grant P30 DK034987) and DuPont Nutrition and Health.