Reduced water availability in India due to groundwater depletion and climate change could threaten the livelihoods of more than one-third of the country’s 1.4 billion residents and has global implications. India recently overtook China to become the world’s most populous nation and is the second-largest global producer of common cereal grains including rice and wheat.

“We find that farmers are already increasing irrigation use in response to warming temperatures, an adaptation strategy that has not been accounted for in previous projections of groundwater depletion in India,” said study senior author Meha Jain, assistant professor at U-M’s School for Environment and Sustainability. “This is of concern, given that India is the world’s largest consumer of groundwater and is a critical resource for the regional and global food supply.”

The lead author is Nishan Bhattarai of the Department of Geography and Environmental Sustainability at the University of Oklahoma, formerly a postdoctoral researcher in Jain’s U-M lab.

The study, scheduled for online publication Sept. 1 in the journal Science Advances, analyzed historical data on groundwater levels, climate and crop water stress to look for recent changes in withdrawal rates due to warming. The researchers also used temperature and precipitation projections from 10 climate models to estimate future rates of groundwater loss across India.

Previous studies have focused on the individual effects of climate change and groundwater depletion on crop production in India. Those studies did not account for farmer decision-making, including how farmers may adapt to changing climate through changes in irrigation decisions.

The new study takes into account the fact that warmer temperatures may increase water demand from stressed crops, which in turn may lead to increased irrigation by farmers.

“Using our model estimates, we project that under a business-as-usual scenario, warming temperatures may triple groundwater depletion rates in the future and expand groundwater depletion hotspots to include south and central India,” Bhattarai said.

“Without policies and interventions to conserve groundwater, we find that warming temperatures will likely amplify India’s already existing groundwater depletion problem, further challenging India’s food and water security in the face of climate change.”

Previous studies found that climate change could decrease the yield of staple Indian crops by up to 20% by mid-century. At the same time, the country’s groundwater is being depleted at an alarming rate, primarily because of water withdrawal for irrigation.

For the newly published study, the researchers developed a dataset that contains groundwater depths from thousands of wells across India, high-resolution satellite observations that measured crop water stress, and temperature and precipitation records.

Most climate models call for increased temperature, increased monsoon (June through September) precipitation and decreased winter precipitation in India over the coming decades. The U-M-led research team found that warming temperatures coupled with declining winter precipitation more than offset added groundwater recharge from increased monsoon precipitation, resulting in accelerated groundwater declines.

Across various climate-change scenarios, their estimates of groundwater-level declines between 2041 and 2080 were more than three times current depletion rates, on average.

In addition to Jain and Bhattarai, authors of the Science Advances study are David Lobell of Stanford University, Balwinder Singh of the International Maize and Wheat Improvement Center in India and the Department of Primary Industries and Regional Development in Western Australia, Ram Fishman of Tel Aviv University, William Kustas of the U.S. Department of Agriculture and Yadu Pokhrel of Michigan State University.

The research was funded by a NASA Land-Cover Land-Use Change Grant and a NASA new investigator program award to Jain. It was supported in part by the U.S. Department of Agriculture’s Agricultural Research Service.

The many environmental responses to the Arctic dipole are described in a paper published online today in the journal Science. This analysis helps explain how North Atlantic water influences Arctic Ocean climate. Scientists call it Atlantification.

The research is led by professor Igor Polyakov of the University of Alaska Fairbanks College of Natural Science and Mathematics. He is also affiliated with the International Arctic Research Center at UAF.

Co-authors include Andrey V. Pnyushkov, research assistant professor at the International Arctic Research Center; Uma S. Bhatt, atmospheric sciences professor at the UAF Geophysical Institute and UAF College of Natural Science and Mathematics; and researchers from Massachusetts, Washington state, Norway, and Germany.

“This is a multidisciplinary view on what’s going on in the Arctic and beyond,” Polyakov said of the new research. “Our analysis covered the atmosphere, ocean, ice, changing continents and changing biology in response to climate change.”

A wealth of data, including direct instrumental observations, reanalysis products and satellite information going back several decades, shows that the Arctic dipole alternates in an approximately 15-year cycle and that the system is probably at the end of the present regime.

In the Arctic dipole’s present “positive” regime, which scientists say has been in place since 2007, high pressure is centered over the Canadian sector of the Arctic and produces clockwise winds. Low pressure is centered over the Siberian Arctic and features counterclockwise winds.

This wind pattern drives upper ocean currents, with year-round effects on regional air temperatures, atmosphere-ice-ocean heat exchanges, sea-ice drift and exports, and ecological consequences.

The authors write that, “Water exchanges between the Nordic seas and the Arctic Ocean are critically important for the state of the Arctic climate system” and that sea ice decline is “a true indicator of climate change.”

In analyzing oceanic responses to the wind pattern since 2007, the researchers found decreased flow from the Atlantic Ocean into the Arctic Ocean through the Fram Strait east of Greenland, along with increased Atlantic flow into the Barents Sea, located north of Norway and western Russia.

The new research refers to these alternating changes in the Fram Strait and the Barents Sea as a “switchgear mechanism” caused by the Arctic dipole regimes.

The researchers also found that counterclockwise winds from the low-pressure region under the current positive Arctic dipole regime drive freshwater from Siberian rivers into the Canadian sector of the Arctic Ocean.

This westward movement of freshwater from 2007 to 2021 helped slow the overall loss of sea ice in the Arctic compared to 1992 through 2006. The freshwater layer’s depth increased, making it too thick and stable to mix with the heavier saltwater below. The thick layer of freshwater prevents the warmer saltwater from melting sea ice from the bottom.

The authors write that the switchgear mechanism regulating inflows of sub-Arctic waters has “profound” impacts on marine life. It can lead to potentially more suitable living conditions for sub-Arctic boreal species near the eastern part of the Eurasian Basin, relative to its western part.

“We are beyond the peak of the currently positive Arctic dipole regime, and at any moment it could switch back again,” Polyakov said. “This could have significant climatological repercussions, including a potentially faster pace of sea-ice loss across the entire Arctic and sub-Arctic climate systems.”

The research was funded by the U.S. National Science Foundation and the U.S. Office of Naval Research.

A major limitation in behavioural research is that scientists can either study animals under highly-controlled, yet often unrealistically simplified and small, environments in the lab, or in largely uncontrolled conditions in the wild. This has limited our ability to study many facets of behaviour, including collective behaviour — the movements and interactions among animals that underlie their complex social lives. What is needed to address this? First, a place with lots of space. Second, state of the art technology.

Both are available in an 18th-century barn at the Max Planck Institute of Animal Behavior in Möggingen near Konstanz and now in the Imaging Hangar, a hall the size of a gymnasium at the University of Konstanz. Both labs are used to closely examine the group behaviour of animals. To do so in a multidimensional way, researchers from the Cluster of Excellence Centre for the Advanced Study of Collective Behaviour at the University of Konstanz and the Max Planck Institute of Animal Behavior have developed a tool called SMART-BARN.

SMART-BARN is an acronym for Scalable Multimodal Arena for Real-time Tracking Behaviour of Animals in large numbers. “It is a new tool that allows studying complex behaviour traits of an individual or interactions between groups of animals like insects, birds, or mammals,” says Hemal Naik. Together with Máté Nagy, Co-Speaker of the Cluster, Iain Couzin, and colleagues developed SMART-BARN. The team was very interdisciplinary: Biologists, physicists, engineers and computer scientists developed it together.

Máté Nagy explains the tool further: “We are using high throughput measurement techniques like optical and acoustic tracking, with which we can study the exact 3D position and posture of animals and calculate their field of view.” Users of the new facility will have the flexibility to perform different experimental paradigms by leveraging the modular nature of the system.

Why scale matters

“SMART-BARN is designed to enhance the scale of typical indoor behavioural experiments in terms of experimental volume and measured behaviour traits and group sizes,” computer scientist Hemal Naik says and adds: “This means that users can measure previously unseen behaviour repertoire because animals have more space.” The facility can — depending on the size of the animals — host 100s of animals simultaneously and extend the possibility of experiments to novel species typically not studied in indoor environments. “In fact, we have now scaled this to work with many thousands of animals,” adds Couzin, “We recently conducted a study in the Imaging Hangar where we tracked 10,000 plague locusts. This would have been impossible without our SMART-BARN technology.”

How SMART-BARN can be used

So far, SMART-BARN was used within different experimental use cases involving subjects as diverse as pigeons, starlings, moth, bats, and humans. Naik is delighted because: “The facility is shaping important new interdisciplinary collaborations.” He continues: “For example, SMART-BARN offers the ability to track 3D gaze and posture of birds in a group of ten or more while maintaining their identity. This technique is being used by researchers to explore the role of gaze in decision making.” The same technique is used by computer scientists to design novel computer vision and AI based algorithms facilitating 3D tracking of animals without attaching any markers to them. “Our method has resulted in an even larger system in the Imaging Hangar at the University of Konstanz to track swarms of robots or thousands of insects,” says Iain Couzin.

Máté Nagy says: “In a nutshell, the scope of its applications is only limited by our ability to come up with ideas of experimentation.” The team imagines the facility to be a collaborative space where researchers from all over the globe can contribute to the exploration of behavioural questions. Therefore, the team invites researchers across the world to connect with them and plan experiments.

Immunologic threats like germs or toxins can arise everywhere inside the human body. Luckily, the immune system — our very own protective shield — has its intricate ways of coping with these threats. For example, a crucial aspect of our immune response involves the coordinated collective movement of immune cells during infection and inflammation. But how do our immune cells know which way to go?

A group of scientists from the Sixt group and the Hannezo group at the Institute of Science and Technology Austria (ISTA) addressed this question. In their study, published today in Science Immunology, the researchers shed light on the immune cells’ ability to collectively migrate through complex environments.

Dendritic cells — The Messengers

Dendritic cells (DCs) are one of the key players in our immune response. They function as a messenger between the innate response — the body’s first reaction to an invader, and the adaptive response — a delayed reaction that targets very specific germs and creates memories to fight off future infections. Like detectives, DCs scan tissues for intruders. Once they locate an infection site, they are activated and immediately migrate to the lymph nodes, where they hand over the battle plan and initiate the next steps in the cascade. Their migration towards the lymph nodes is guided by chemokines — small signaling proteins released from lymph nodes — that establish a gradient. In the past, it was believed that DCs and other immune cells react to this external gradient, moving along towards a higher concentration. However, novel research conducted at ISTA now challenges this notion.

One receptor — two functions

The scientists took a close look at a receptor — a surface structure found on activated DCs called “CCR7.” CCR7’s essential function is to bind to a lymph node-specific molecule (CCL19), which triggers the next steps of the immune response. “We found that CCR7 not only senses CCL19 but also actively contributes to shaping the distribution of chemokine concentrations,” Jonna Alanko, a former postdoc from the lab of Michael Sixt, explains.

Using different experimental techniques, they demonstrated that as DCs migrate, they take up and internalize chemokines via the CCR7 receptor, resulting in local depletion of chemokine concentration. With less signaling molecules around, they move further into higher chemokine concentrations. This dual function allows immune cells to generate their own guidance cues to orchestrate their collective migration more effectively.

Movement depends on cell population

To understand this mechanism quantitatively at the multicellular scale, Alanko and colleagues teamed up with theoretical physicists Edouard Hannezo and Mehmet Can Ucar, also at ISTA. With their expertise in cell movement and dynamics, they established computer simulations that were able to reproduce Alanko’s experiments. With these simulations, the scientists predicted that the dendritic cells’ movement not only depends on their individual responses to the chemokine but also on the density of the cell population. “This was a simple but nontrivial prediction; the more cells there are the sharper the gradient they generate — it really highlights the collective nature of this phenomenon!” says Can Ucar.

Additionally, the researchers found that T-cells — specific immune cells that destroy harmful germs — also benefit from this dynamic interplay to enhance their own directional movement. “We are eager to find out more about this novel interaction principle between cell populations with ongoing projects,” the physicist continues.

Enhancing the immune response

The discoveries are a step in a new direction for how cells move inside our bodies. In contradiction to what was previously believed, immune cells not only respond to chemokines, but they also play an active role in shaping their own environment by consuming these chemical signals. This dynamic regulation of signaling cues provides an elegant strategy to guide their own movement and that of other immune cells.

This research has significant implications for our understanding of how immune responses are coordinated within the body. By uncovering these mechanisms, scientists could potentially design new strategies to enhance immune cell recruitment to specific sites, such as tumor cells or areas of infection.

Flowering for some plants is a yearly occurrence, for others, it is a once-in-a-lifetime event. A widespread species of bamboo in Japan, Phyllostachys nigra var. henonis, takes this one-time flowering event and pushes it to the extreme: they flower once every 120 years before dying to make way for the next generation. Researchers have realized there might be another issue at hand with this monocarpic species, which is the lack of germination of the seeds from a majority of the flowering specimens. Implications of a once dense field of bamboo, something that serves both as a food source and a source of material for crafts, turning to grassland for several years until the regeneration of bamboo begins to start somehow, can impact the ecology of the area in addition to the country’s economy.

Researchers published their results in PLOS ONE on June 12.

Upon the observation of some early flowering specimens, researchers decided to take advantage of this event to take a deeper look at the regeneration ecology since there is no recorded data since the last flowering of this species took place around 1908. It was found that more than 80% of the sampled culms flowered but all the flowering culms did not produce seeds, indicating this variation of P. nigra does not reliably undergo sexual regeneration via the germination of seeds.

“The bamboo did not produce any viable seeds that can germinate. Bamboo shoot production was stopped after flowering. There was no sign of regeneration of this bamboo after flowering for the initial three years” said Toshihiro Yamada, lead researcher and first author of the study.

Around .17 million hectares of Japan are occupied by three species of bamboo, one of them being P. nigra var. henonis. Given that this variety of bamboo isn’t producing viable seeds, it’s likely once this flowering event occurs, there will be wide open areas of grasslands, changing the ecology of the area in addition to reducing the availability of bamboo as a resource.

The environmental impacts of a rapidly shifting ecological area extend past the insects and animals that rely on the food or shelter of the bamboo stand but also can impact the area for years to come considering the potential for soil erosion. Bamboo can help keep soil in place thanks to its strong and widespread rhizomes, so a sudden loss of a large area of this plant can lead to changing topography of the area.

“So, a bamboo stand will turn into a grassland after bamboo flowering for at least several years. We may need to manage this drastic change after bamboo flowering” Yamada said.

There are measures that can be taken to protect the ecological habitat during the time it takes for the bamboo stands to regenerate, such as fertilizer applications or replanting the same bamboo species from non-flowering stands. However, management of the rapidly spreading rhizomatous bamboo can become an issue that would then need to be addressed regularly and somewhat aggressively.

More information to be gained includes addressing why this variety of bamboo doesn’t produce many viable seeds, and from there, considerations made on the longevity of this species as a whole have to be made, too. Furthermore, due to its aggressive spread and intense management required to keep it from overtaking forests and other agricultural areas, the best time to make widespread changes might be after the flowering event when the bamboo is at its weakest.

The research, recently published in the Journal of Glaciology, is the first large-scale study of its kind to compare ice shelf thickness data from ice-penetrating radar measurements to thickness data estimated from contemporary surface elevation measurements.

By juxtaposing vast datasets of 20 of the 300 total separate ice shelf systems that surround about 75% of the Antarctic ice sheet, researchers from The Ohio State University found that on average, the Antarctic ice shelves are nearly 6% thinner than previous studies had assumed, a difference of about 17 meters. This may seem like a small shift in scale, but typical ice shelves can be anywhere from 50 to 600 meters thick.

The study concludes that while prior assumptions about the ice shelves’ thickness were correct on a large scale, their accuracy varied greatly on a small scale, such as for individual structures like valleys or crevasses that are either too narrow or too small to be measured accurately.

Yet as ice shelves play a large role in stabilizing the Antarctic ice sheet as well as Earth’s complex climate system, getting an accurate estimation of their size is essential for calculating how their melt could contribute to sea level rise, said Allison Chartrand, lead author of the study and recent doctoral graduate of the Byrd Polar and Climate Research Center.

“Because the Antarctic ice sheet is so big, a 1% misestimation in how fast it’s melting could mean inches or feet of sea level rise that we’re not accounting for,” she said. “So it’s really important to be as accurate as we can.”

Even the most minute changes to Antarctica’s ice shelves could pose a significant threat to coastal communities, Chartrand said, as a few inches of significantly displaced ice shelf could cause thicker ice to flow into the ocean and potentially cause some coastlines to retreat several feet.

According to Chartrand, she and her co-author, Ian Howat, a glaciologist and a Distinguished University Scholar in earth sciences at Ohio State, first began to investigate ice shelf thickness when examining basal channels — channels in which warmer ocean water melts grooves into the bottom of the ice shelf, accelerating mass loss — during a previous study.

One of the largest discrepancies the study found was that the assumptions used to estimate ice shelf thickness in previous research sometimes exaggerated ice shelf thickness in some areas, and at other times understated it.

While many of these inconsistencies don’t take away much from the big picture, individually, these snapshots are vastly out of focus, said Chartrand. “In comparing the thickness estimate with the radar estimate, we saw that the numbers we had on basal channels and other features like them could be different by up to hundreds of meters, which meant that we could potentially be underestimating or overestimating rates of change,” she said.

Overall, the study concludes that more abundant and accurate data is needed to enable better predictions of ice shelf loss in Antarctica, as the ultimate goal of their work is to improve observations of the processes that contribute to sea level rise, said Chartrand.

“What this research really shows is that we need to be a lot more careful about the assumptions we make to estimate the ice shelf thickness, and about how we account for uncertainties and what they mean for the final result,” she said.

While their work also seeks to inspire others to probe into older datasets, Chartrand hopes that using the past to study the future changes in our environment spurs the development of more advanced technologies, ones that might be able to offer greater aid in the task of assessing the ups and downs of Antarctica’s ever-shifting landscape.

“There’s potential for new discoveries even with data collected anywhere from two to 15 years ago, so we know that a lot still hasn’t been fully explored,” said Chartrand.

This study was supported by NASA and the National Science Foundation.

“Although we finally recognize that environmental chemicals impact women’s health, most studies have focused on men’s reproductive health and very few studies have looked at how these chemicals affect women,” said Jodi Flaws (EIRH co-leader/MME), a professor of comparative biosciences. “Our paper is novel because we are the first to look at this aspect of reproduction.”

For their study, the researchers chose a DiNP dose that humans are exposed to on a daily basis. They exposed pregnant female mice to DiNP orally for their first week of pregnancy, which is analogous to the first trimester in humans.

“I chose this window because most women don’t know from day one that they are pregnant. As a result, they maintain their general lifestyle for a while and may become more careful once they know that they are pregnant. During that time, however, they will continue to be exposed to DiNP,” said Arpita Bhurke, a postdoctoral fellow in the Bagchi lab and the first author of the paper.

In the early stages of pregnancy, the embryo attaches to the uterus and embeds in the maternal tissue, which supports the growth and development of the embryo. The process also stimulates the formation of new blood vessels, ensuring that the embryo has an adequate supply of oxygen and nutrients from the mother. Using tissue-staining techniques, the researchers found that DiNP exposure impairs the formation of blood vessels in both the maternal tissue and the placenta.

“In mice, these maternal blood vessels are formed after the first week of pregnancy and they have been exposed to DiNP before this development happens,” said Indrani Bagchi (EIRH co-leader), a Billie Field Professor of Reproductive Biology. “As a result, the tissue formation is effected and it creates a ripple effect, impairing embryo growth.”

The impact of DiNP on the placenta had several consequences later on in the pregnancy. The researchers found that pregnant mice that had been exposed to DiNP had smaller litter sizes and shorter gestation periods. Mice that were fed corn oil instead of DiNP produced an average of 16 pups per litter, whereas DiNP-fed mice produced 11 pups, and on average the pups weighed less. Additionally, instead of delivering their litter in 20 days, DiNP-fed mice were giving birth 18-24 hours earlier.

“We know that DiNP causes defects in the formation of the placenta. However, it is unclear whether this is due to the effect of DiNP on the embryo or on the maternal tissue or both. We want to address this question in our future work,” Bagchi said.

The researchers are also interested in deciphering how the chemicals impact the uterine tissue and litter birth. “I will focus on cell culture systems because we want to distinguish between the embryo and the maternal tissue effects. By using just the cells, we can better understand how DiNP is impacting the placenta in both early and late stages of pregnancy,” Bhurke said.

It’s an issue in the news, as toxic mold spawned by the moisture left behind by flood waters from Hurricane Idalia could lead to severe health problems for people who suffer from chemical intolerance. This mold also could initiate the condition in some individuals.

“Everyone should avoid prolonged exposure to mold whenever possible,” said physician-researcher Claudia Miller, MD, MS, from The University of Texas Health Science Center at San Antonio, also called UT Health San Antonio. “Research has increasingly shown that toxic mold is much more dangerous than was previously recognized.”

In the survey, published in the journal Environmental Sciences Europe, 17.5% of participants who attributed their illness to an initiating event cited mold exposure as the perceived cause of their chemical intolerance. CI is estimated to afflict up to 20% to 30% of Americans, Miller, senior author of the study, said.

Participants were queried about antibiotic use, as well. According to the results, prolonged courses of antibiotics were associated with an increased risk of CI.

The survey data also indicate that with each additional initiating exposure respondents can recall, the odds of their reporting CI nearly triple.

“With climate change contributing to more severe storms and more intense flooding worldwide, the danger posed by toxic mold is likely to increase dramatically in the near future,” Miller said. “As mold exposure is known to be a major initiator, the likelihood of more and more people with chemical intolerance is also unfortunately on the rise.”

TILT

The study furthers understanding about how a two-stage disease process called TILT (toxicant-induced loss of tolerance) begins. The survey asked 10,981 people to state their self-perceptions about the events that began the downward spiral through TILT and into chemical intolerance.

“TILT can develop rapidly, for instance after a pesticide exposure, or gradually if someone is working or living in a setting such as a moldy building,” Miller said. She first proposed TILT in 1996 and is professor emerita of family and community medicine at UT Health San Antonio.

Unknown origins

“Initiating events commonly go unrecognized and therefore unreported, leaving triggers and symptoms as the only documented components,” Miller said. “This has thwarted our understanding of the actual causes of TILT.”

Participants completed an 80-question online survey called the Personal Exposure Inventory. It included items concerning individuals’ medical diagnoses and personal exposures including antibiotic use.

Chemical intolerance was assessed using the Quick Environmental Exposure and Sensitivity Inventory (QEESI©) developed by Miller 25 years ago. It is a validated, self-administered questionnaire now used worldwide to differentiate individuals with CI from the general population. One-fifth of survey respondents met the QEESI criteria for chemical intolerance.

Toxic mold

Exposure to mold was the most frequently mentioned initiating event on the Personal Exposure Inventory. “In recent years, global warming has led to more rainfall, floods, hurricanes, roof leaks and water intrusion, resulting in increased mold growth indoors,” said paper co-author Raymond F. Palmer, PhD, a biostatistician and professor of family and community medicine at UT Health San Antonio.

Mold was followed in rank order by exposures to pesticides (cited by 13.8% of respondents), medical/surgical procedures (12.6%), remodeling/new construction (12.0%), fires/combustion products (7.2%) and breast implants (1.8%).

Antibiotics

Respondents answered questions pertaining to how many courses of antibiotics they had completed for specific types of infections. Antibiotics prescribed for infections categorized as skin, tonsil, gastrointestinal, prostate, sinus, wound and pneumonia were most strongly associated with chemical intolerance.

“Our search for the underlying causes of CI represents a much-needed addition to the CI/TILT literature, whose principal focus has been on triggers that elicit CI symptoms from day to day with no attempt to determine what initiated TILT,” Miller said.

‘A cohesive narrative’

“Taken together, our data support the idea that the person who reports multiple symptoms, multiple intolerances and recurrent infections as well as a history of exposure events is sharing a cohesive narrative, one that points to physiological (as opposed to psychosomatic) explanations of their oft-confusing complaints,” she said.

Although certain exposures such as medical/surgical procedures may be difficult to avoid, reducing exposures to contaminants related to pesticide use, new construction/remodeling and mold is possible and should be the focus of efforts to prevent future CI/TILT, the authors wrote.

Digging in

Finally, they encourage practitioners who see patients with medically unexplained symptoms — currently one in four primary care patients — to consider administering the QEESI. “‘TILTed’ individuals who report brain fog, memory, mood and concentration difficulties often receive referrals to psychiatrists, psychologists or social workers who explore their psychosocial environments but do not ask about changes in their actual — physical and chemical — environments,” Miller said. “If initiating exposures such as pesticides, toxic mold, implants and combustion products are not stopped, sensitivities can spiral out of control.”

Teaching in schools of medicine, public health, architecture and engineering has not kept pace with these toxicants, many of which are new to the planet since World War ll, Miller noted. This is exacerbated by energy conservation efforts that have increased exposures to indoor air toxicants, she said.

Marilyn Brachman Hoffman

In their acknowledgments, the authors “thank the Marilyn Brachman Hoffman Foundation for generously funding this study and Marilyn Hoffman for her prescient bequest prioritizing research on toxicant-induced loss of tolerance. We are deeply grateful to the patients who participated in this groundbreaking study.”

Hoffman’s bequest specified research on TILT. “She suffered terribly from chemical, food and drug intolerances herself, but especially from not being believed by family members and her doctors,” Miller said. “She was a citizen-scientist who read all my papers and book, “Chemical Exposures: Low Levels and High Stakes,” co-authored with Nicholas Ashford, PhD, JD, of the Massachusetts Institute of Technology.

“More than anything, Mrs. Hoffman wanted to discover the biomechanism for TILT,” Miller said. “She knew that it was essential for helping patients like herself. Her bequest has led to publication of the biomechanism for TILT in a series of papers over the past two years in Environmental Sciences Europe, a journal read by regulatory toxicologists around the world.”

If you suspect that you or a loved one has developed chemical intolerance or TILT, answer this brief, three yes-or-no question screening test, called BREESI. A positive response to any of the questions should lead to taking the more extensive, validated diagnostic questionnaire, the QEESI, or Quick Environmental Exposure and Sensitivity Inventory. People who have high scores on the QEESI are seen as likely to be chemically intolerant and are encouraged to share the information with their health care providers.

In people with tumors that originated in other parts of the body but spread to the brain, treatment with a type of immunotherapy called immune checkpoint blockade appears to elicit a significant increase in both active and exhausted T cells — signs that the T cells have been triggered to fight the cancer. The reason the same thing doesn’t occur in people with glioblastoma is that anti-tumor immune responses are best initiated in draining lymph nodes outside of the brain, and that process does not occur very effectively in glioblastoma cases.

To date, immunotherapy has not been effective in treating glioblastoma, but it has been shown to slow or even eradicate other types of cancer, such as melanoma, which frequently metastasizes to the brain.

The new research, published in the Journal of Clinical Investigation, could help improve the effectiveness of immunotherapy for people with brain tumors and it could suggest new paths in the effort to help develop more effective therapies.

“If we’re going to try to develop new therapies for solid tumors, like glioblastoma, which are not typically responsive, we need to understand the tumor types that are responsive, and learn the mechanisms by which that happens,” said the study’s senior author, Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA.

The researchers studied the immune cells obtained from nine people with metastatic brain tumors who had been treated with immune checkpoint blockade — which works by harnessing the body’s immune system to destroy cancer cells — and compared their observations with immune cells taken from 19 patients with brain metastases that not been treated with immunotherapy.

They used a technique called single-cell RNA sequencing to examine the genetic material in both sets of samples, and then compared the data to previously published analyses of 25 recurrent glioblastoma tumors to better understand the effect the immunotherapy had on T cells.

“We really were trying to figure out which immune cells are changing in the more responsive tumors in order to better explain the higher response rate to the treatment,” said the study’s co-first author, Lu Sun, a project scientist in the Geffen School of Medicine’s neurosurgery department. “No study has comprehensively examined the differential effect of immune checkpoint blockade treatment on these two types of brain tumors before.”

In the tumors that had spread to the brain, the researchers saw that the T cells had specific characteristics associated with fighting tumors entering the brain, most likely due to a more effective priming step that occurs outside of the brain.

Before traveling to the brain, T cells are first activated in the lymph nodes. During this process, a type of immune cells called dendritic cells share information about the tumor to T cells so they can better attack the tumor. This priming process, however, doesn’t work very effectively when doctors attempt to use immune checkpoint blockade for treating glioblastoma.

The researchers also found that a specific subgroup of those exhausted T cells was associated with longer overall survival in people whose cancer had metastasized to the brain.

“We found quite a significant difference between the two types of brain tumors and how they respond to immunotherapies,” said study author Dr. Won Kim, surgical director of UCLA Health’s brain metastasis program and a member of the Jonsson Cancer Center. “There was a tremendous number of T cell lymphocytes that were found within brain metastases following immunotherapy, and while the number of T cell lymphocytes also increased in glioblastoma patients, it wasn’t anywhere near the same extent.”

Prins, who is also a researcher at the Jonsson Cancer Center, said that finding “suggests that enhancing the activation and presentation of T cells by dendritic cells could be a potential treatment strategy.”

In future studies, the researchers plan to analyze data from a larger, more uniform group of people who were diagnosed with melanoma that had spread to the brain.

The study’s other co-first author is Jenny Kienzler, who was a UCLA fellow in neurosurgery when the research was conducted. Other UCLA authors are Jeremy Reynoso, Alexander Lee, Eileen Shiuan, Shanpeng Li, Jiyoon Kim, Lizhong Ding, Amber Monteleone, Geoffrey Owens, Dr. Richard Everson, David Nathanson, Dr. Timothy Cloughesy, Gang Li, Dr. Linda Liau and Willy Hugo.

The research was supported by grants from the National Institutes of Health Specialized Programs of Research Excellence in Brain Cancer, National Cancer Institute, National Institutes of Health National Center for Advancing Translational Science, Parker Institute for Cancer Immunotherapy, Brain Tumor Funder’s Collaborative and Cancer Research Institute.