The trend — and a 2014 mandate for sustainable groundwater management in the state — has ignited interest in replenishing aquifers in California’s Central Valley through managed flooding of the ground above them. But until now there has been no reliable way to know where this type of remedy will be most effective. New research from Stanford University suggests a way to map precisely where and how to use groundwater recharge to refill the aquifers and stop the sinking.

Parts of the Central Valley sunk by as much as 28 feet during the first half of the 20^th century, and in recent decades some locations have dropped by nearly 8 inches per year. Modeling in the new study, published in the peer-reviewed journal Water Resources Research, indicates the ground will sink by another 13 feet or more at some sites over the next 20 years unless pumping slows down.

Even under a scenario where pumping never exceeds the amount of water going into aquifers, the model predicts continued sinking as past overdrafts take their toll. “There is a time delay in the system,” said geophysicist Rosemary Knight, senior author on the study and a professor at Stanford’s School of Earth, Energy & Environmental Sciences. “The only way we can stop it is to be strategic about what we do with our available recharge water.”

A perfect storm

In a normal year, water in canals, reservoirs and rivers is sufficient for most irrigation in the Central Valley, while aquifers provide a supplement. In recent drought years, however, surface supplies came up short and farmers contributing to the region’s $17 billion agricultural industry relied more heavily on groundwater.

“It’s a perfect storm of an extensive agricultural industry combined with low precipitation, warm temperatures, the need for pumping groundwater and an abundance of clay that is prone to subsidence,” said Knight. Clays here that compact when pumped dry also tend to be rich in arsenic, which intensive pumping can release into water supplies. “So you have problems with water quantity and water quality,” Knight said.

Recharge methods now in use or under serious consideration in California involve flooding fields or orchard groves during the winter months or creating year-round recharge ponds. “The key question is where does the water go?” Knight said. “If you’re going to flood a farmer’s field, you should be sure it’s going to work.”

Knowing where water will go underground depends on mapping the intricate channels of sand and gravel that interlace tightly packed clays and silts. In California, that information often comes from drilling contractors’ reports to state regulators, which are expensive to acquire and do not cover areas between or beneath the drilled wells. As a result, the most common approach to dealing with subsidence is reactive. “If we are proactively managing then we can prevent unrecoverable storage loss,” said lead author Ryan Smith, a professor at Missouri University of Science and Technology who completed the research as a PhD student in geophysics at Stanford.

Above and below ground

The new approach, based on a marriage of two types of remote sensing data, could be applied across large agricultural regions at relatively low cost. Knight and Smith analyzed the structure of sand and clay layers that had been measured in a previous study by transmitting electromagnetic signals from a helicopter at three sites in Tulare County, about 45 miles south of Fresno, California. They also processed data from public satellite images to measure how much the ground had sunk.

“I realized that both of the datasets were linked to clay content,” Smith said. “I thought, if there’s a mathematical way to connect these two, then we could build a predictive model of subsidence.” The study describes a method for adapting existing math and physics algorithms to integrate the two datasets into one model.

Only a sliver of California has been mapped with both types of remote sensing data, noted Tim Godwin, a senior engineering geologist with the California Department of Water Resources, which has supported Knight’s efforts to expand airborne electromagnetic surveys in the state. But as these datasets grow, he said, coupling them with tools to predict sinking will help answer questions about the best ways to meet sustainability goals. “Groundwater managers will be able to more accurately predict susceptibility to subsidence conditions and have greater confidence in proposed projects,” he said.

According to Smith, subsidence in the coming years could be even more severe than the current model indicates if drillers deepen the region’s wells to cope with future water shortages. “There are still deeper, largely untapped aquifers that, if pumped, would have a dramatic pressure loss,” he said. “That would cause the clays to compact more than they do in the portions of the aquifer being used today.”

LDL cholesterol is called bad cholesterol because it can lead to fatty build-up in the arteries. The study also found that women with the lowest triglyceride levels, a fat found in the blood, had an increased risk of hemorrhagic stroke compared to those with the highest triglyceride levels.

Hemorrhagic strokes, also known as bleeding strokes, are much less common than ischemic strokes, when blood flow is blocked to the brain. They are also more difficult to treat and therefore more likely to be deadly.

“Strategies to lower cholesterol and triglyceride levels, like modifying diet or taking statins, are widely used to prevent cardiovascular disease,” said study author Pamela Rist, ScD, of Brigham and Women’s Hospital in Boston and a member of the American Academy of Neurology. “But our large study shows that in women, very low levels may also carry some risks. Women already have a higher risk of stroke than men, in part because they live longer, so clearly defining ways to reduce their risk is important.”

The study involved 27,937 women age 45 and older enrolled in the Women’s Health Study who had total cholesterol, LDL cholesterol, high density lipoprotein (HDL) cholesterol, which is known as good cholesterol, and triglycerides measured at the start of the study. Researchers then reviewed medical records to determine how many women had a bleeding stroke.

With an average of 19 years of follow-up, researchers identified 137 women who had a bleeding stroke.

Nine out of 1,069 women with cholesterol 70 mg/dL or lower, or 0.8 percent, had a bleeding stroke, compared to 40 out of 10,067 women with cholesterol 100 mg/dL up to 130 mg/dL, or 0.4 percent. After adjusting for other factors that could affect risk of stroke, such as age, smoking status, high blood pressure and treatment with cholesterol-lowering medications, researchers found that those with very low LDL cholesterol were 2.2 times more likely to have a bleeding stroke.

For triglyceride levels, researchers divided the women into four groups. Women in the group with the lowest levels had fasting levels 74 mg/dL or lower, or non-fasting levels of 85 mg/dL or lower. Women in the group with the highest levels had fasting levels that were higher than 156 mg/dL, or non-fasting levels that were higher than 188 mg/dL.

Researchers found that 34 women of the 5,714 women with the lowest levels of triglycerides, or 0.6 percent, had a bleeding stroke, compared to 29 women of the 7,989 with the highest triglycerides, or 0.4 percent. After adjusting for other factors that could affect risk, researchers found that those with the lowest triglycerides were twice as likely to have a bleeding stroke.

No difference in risk was found for total cholesterol or HDL cholesterol.

“Women with very low LDL cholesterol or low triglycerides should be monitored by their doctors for other stroke risk factors that can be modified, like high blood pressure and smoking, in order to reduce their risk of hemorrhagic stroke,” Rist said. “Also, additional research is needed to determine how to lower the risk of hemorrhagic stroke in women with very low LDL and low triglycerides.”

One limitation of the study was that cholesterol and triglyceride levels were only measured once at the beginning of the study. Also, a large number of the women had already reached menopause when those levels were measured, which prevented researchers from examining whether menopause status may influence the link between cholesterol and triglyceride levels and bleeding stroke.

The study was supported by the National Institutes of Health.

Like city streets with no garbage collection, cells can get choked if autophagy is not working properly. The autophagy process is controlled by a biological signaling pathway called mTOR. Greater than normal activation of mTOR is associated with several neurological disorders, and mutations in some components have been found in patients with ASD. The researchers from CBS thus had an inkling that abnormal protein cleanup affects how neurons work and can lead to downstream manifestations of psychiatric symptoms. Their study, published on April 10 in the open-access journal Science Advances, confirms that social behavior deficits in mice can result from a breakdown in autophagy and a build-up of unwanted protein.

For autophagy to begin, cells need to contain a protein encoded by the gene Atg7. The researchers made knockout mice by selectively deleting this gene from two cell populations, excitatory and inhibitory interneurons, which are known to be the malfunctioning culprits in many neurodevelopmental and neuropsychiatric disorders. The mice in both groups displayed overlapping behavioral abnormalities such as increased anxiety and reduced social interaction and nesting. “The loss of autophagy in different types of neurons had the same behavioral effects, which hinted that a common mechanism was at work,” says Motomasa Tanaka, senior author and team leader at RIKEN CBS.

Picking through the cellular ‘trash’ that accumulated in the affected cells, the researchers identified aggregates of proteins made up of GABARAPs, a group of proteins that help bring receptors for the main inhibitory neurotransmitter GABA to the cell surface. Not only had these proteins accumulated, they were being dumped into p62+ aggregates, formed when autophagy is disrupted in cells. “Think of autophagy as the recycling depot and p62 as the garbage trucks that go around the cell to pick up trash labelled for recycling,” explains first author Kelvin Hui. “When the recycling depot experiences a shutdown or reduced capacity, p62 has nowhere to bring this garbage and it starts to pile up in the cell, leading to major problems.”

The major problem in this case is that neurons could not communicate normally: with trapped GABARAPs, the GABA receptors were not transported to the cell surface and the neurons became hyperactive. The research team also looked at post-mortem human brain samples from a subset of patients with ASD and observed the same protein aggregation and increase of p62. This finding, together with previous research on genetic deletions in patients with ASD and intellectual disability, further implicates disrupted autophagy and protein aggregation in the pathogenesis of these conditions.

“This is the first demonstration of a link between mTOR-autophagy and GABA signaling,” notes Hui. “Changes in these processes are also seen in cancer and diabetes, so it is of great clinical importance to examine whether the molecular mechanism that we have uncovered here is also involved in those diseases.” Given the role of protein aggregation in neuronal and behavioral abnormalities, the research team views small molecules that can disrupt the harmful protein aggregation as potential novel therapeutic factors for neurodevelopmental and neuropsychiatric disorders.

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