A new study led by Dr. Natalie Johnson, associate professor in the Texas A&M University School of Public Health’s Department of Environmental and Occupational Health, shows that exposure to ultrafine particles (UFPs) during pregnancy enhances respiratory viral infection risk. The results of the study were published recently in Particle and Fibre Toxicology.

“We know that air pollution affects the pulmonary immune system, making individuals more susceptible to viral infections,” Johnson said. “We also know pregnant women are already at increased risk for severe flu. Surprisingly, studies have not interrogated the combined effects of pregnancy, air pollution and influenza. Our findings demonstrate the need to further study these interactions in order to prevent short and perhaps long-term impacts on maternal health.”

In the study, Johnson and her co-authors point out that there are several physiological characteristics that explain maternal susceptibility to viral infection. Among those are increased cardiac output and decreased tidal volume — the amount of air that moves in or out of the lungs with each respiratory cycle — as well as immunological changes such as selective modulation of immune cell subsets to protect the developing fetus.

The research team also highlights that vaccination compliance during pregnancy is generally below 50 percent, despite vaccination against influenza being safe and effective, leading to increased risk for developing respiratory infection.

As a result, air pollution, which is a worldwide environmental health issue, is responsible for one in nine deaths with an annual premature mortality of more than 7 million. A mixture of gases and tiny airborne particulate matter, which is categorized as UFPs, are critical to recognize and identify, especially to protect vulnerable populations.

The research team says these findings support future clinical and regulatory interventions for protecting pregnant women and controlling UFPs. According to the researchers, it is imperative that pregnant women in urban cities, where influenza and UFPs are more prevalent, are provided vaccinations and preventive measures limiting UFP exposure to protect maternal health.

“Air pollution is a pervasive environmental health issue,” Johnson said. “Strategies to protect the most vulnerable, like pregnant women, are of high priority to decrease adverse health effects.”

Additional authors include Nicholas L. Drury, Texas A&M Department of Environmental and Occupational Health and Texas A&M Department of Nutrition; Toriq Mustapha, Texas A&M Department of Environmental and Occupational Health; Ross A. Shore, Texas A&M Department of Environmental and Occupational Health, Jiayun Zhao, Texas A&M Department of Chemistry; Gus A. Wright, Texas A&M Department of Veterinary Pathobiology; Aline Rodrigues Hoffmann, University of Florida Department of Comparative, Diagnostic, and Population Medicine; Susanne U. Talcott, Texas A&M Department of Nutrition; Annette Regan, University of San Francisco School of Nursing and Health Professions; Robert M. Tighe, Duke University Department of Medicine; and Renyi Zhang, Texas A&M Department of Chemistry and Texas A&M Department of Atmospheric Sciences.

Grambank was constructed in an international collaboration between the Max Planck institutes in Leipzig and Nijmegen, the Australian National University, the University of Auckland, Harvard University, Yale University, the University of Turku, Kiel University, Uppsala University, SOAS, the Endangered Languages Documentation Programme, and over a hundred scholars from around the world. Grambank’s coverage spans 215 different language families and 101 isolates from all inhabited continents. “The design of the feature questionnaire initially required numerous revisions in order to encompass many of the diverse solutions that languages have evolved to code grammatical properties,” says Hedvig Skirgård, who coordinated much of the coding and is the lead author of the study.

Limits on variation

The team settled on 195 grammatical properties, ranging from word order to whether or not a language has gendered pronouns. For instance, many languages have separate pronouns for ‘he’ and ‘she’, but some also have male and female versions of ‘I’ or ‘you’. The possible ‘design space’ would be enormous if grammatical properties were to vary freely. Limits on variation could be related to cognitive principles rooted in memory or learning, rendering some grammatical structures more likely than others. Limits could also be related to historical ‘accidents’, such as descent from a common language or contact with other languages.

The researchers discovered much greater flexibility in the combination of grammatical features than many theorists have assumed. “Languages are free to vary considerably in quantifiable ways, but not without limits,” explains Stephen Levinson, Director emeritus of the Max Planck Institute for Psycholinguistics in Nijmegen and one of the founders of the Grambank project. “A sign of the extraordinary diversity of the 2400 languages in our sample is that only five of them occupy the same location in design space (share the same grammatical properties).”

Languages show much greater similarity to those with a common ancestor than those they are in contact with. “Genealogy generally trumps geography,” says Russell Gray, Director of the Department of Linguistic and Cultural Evolution and senior author of the study. “Nevertheless, if processes of linguistic evolution and diversification were run again from the beginning, there would still be some resemblance to what we now have. The constraints of human cognition mean that, while there is a great deal of historical contingency in the organisation of grammatical structures, there are regular patterns as well.”

Diversity under threat

“The extraordinary diversity of languages is one of humanity’s greatest cultural endowments,” concludes Levinson. “This endowment is under threat, especially in some areas such as Northern Australia, and parts of South and Northern America. Without sustained efforts to document and revitalise endangered languages, our linguistic window into human history, cognition and culture will be seriously fragmented.”

The Grambank database is an open-access comprehensive resource maintained by the Max Planck Society. “It puts linguistics on an even footing with genetics, archaeology and anthropology in terms of quantitative, large scale, accessible data,” says Gray. “I hope it will facilitate the exploration of links between linguistic diversity and a broad array of other cultural and biological traits, ranging from religious beliefs to economic behavior, musical traditions and genetic lineages. These links with other facets of human behavior will make Grambank a key resource not only in linguistics, but in the multidisciplinary endeavour of understanding human diversity.”

One of the first brain regions to show neurodegeneration in Alzheimer’s disease is a part of the hypothalamus called the mammillary body. In a new study, MIT researchers have identified a subset of neurons within this body that are most susceptible to neurodegeneration and hyperactivity. They also found that this damage leads to memory impairments.

The findings suggest that this region may contribute to some of the earliest symptoms of Alzheimer’s disease, making it a good target for potential new drugs to treat the disease, the researchers say.

“It is fascinating that only the lateral mammillary body neurons, not those in the medial mammillary body, become hyperactive and undergo neurodegeneration in Alzheimer’s disease,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the senior author of the study.

In a study of mice, the researchers showed that they could reverse memory impairments caused by hyperactivity and neurodegeneration in mammillary body neurons by treating them with a drug that is now used to treat epilepsy.

Former MIT postdoc Wen-Chin (Brian) Huang and MIT graduate students Zhuyu (Verna) Peng and Mitchell Murdock are the lead authors of the paper, which appears today in Science Translational Medicine.

Predisposed to degeneration

As Alzheimer’s disease progresses, neurodegeneration occurs along with the buildup of amyloid beta plaques and misfolded Tau proteins, which form tangles in the brain. One question that remains unresolved is whether this neurodegeneration strikes indiscriminately, or if certain types of neurons are more susceptible.

“If we could identify specific molecular properties of classes of neurons that are predisposed to dysfunction and degeneration, then we would have a better understanding of neurodegeneration,” Murdock says. “This is clinically important because we could find ways to therapeutically target these vulnerable populations and potentially delay the onset of cognitive decline.”

In a 2019 study using a mouse model of Alzheimer’s disease, Tsai, Huang, and others found that the mammillary bodies — a pair of structures found on the left and right underside of the hypothalamus — had the highest density of amyloid beta. These bodies are known to be involved in memory, but their exact role in normal memory and in Alzheimer’s disease is unknown.

To learn more about the mammillary body’s function, the researchers used single-cell RNA-sequencing, which can reveal the genes that are active within different types of cells in a tissue sample. Using this approach, the researchers identified two major populations of neurons: one in the medial mammillary body and the other in the lateral mammillary body. In the lateral neurons, genes related to synaptic activity were very highly expressed, and the researchers also found that these neurons had higher spiking rates than medial mammillary body neurons.

Based on those differences, the researchers wondered if the lateral neurons might be more susceptible to Alzheimer’s disease. To explore that question, they studied a mouse model with five genetic mutations linked to early-onset Alzheimer’s in humans. The researchers found that these mice showed much more hyperactivity in lateral mammillary body neurons than healthy mice. However, the medial mammillary body neurons in healthy mice and the Alzheimer’s model did not show any such differences.

The researchers found that this hyperactivity emerged very early — around two months of age (the equivalent of a young human adult), before amyloid plaques begin to develop. The lateral neurons became even more hyperactive as the mice aged, and these neurons were also more susceptible to neurodegeneration than the medial neurons.

“We think the hyperactivity is related to dysfunction in memory circuits and is also related to a cellular progression that might lead to neuronal death,” Murdock says.

The Alzheimer’s mouse model showed impairments in forming new memories, but when the researchers treated the mice with a drug that reduces neuronal hyperactivity, their performance on memory tasks was significantly improved. This drug, known as levetiracetam, is used to treat epileptic seizures and is also in clinical trials to treat epileptiform activity — hyperexcitability in the cortex, which increases the risk of seizures — in Alzheimer’s patients.

Comparing mice and humans

The researchers also studied human brain tissue from the Religious Orders Study/Memory and Aging Project (ROSMAP), a longitudinal study that has tracked memory, motor, and other age-related issues in older people since 1994. Using single-cell RNA-sequencing of mammillary body tissue from people with and without Alzheimer’s disease, the researchers found two clusters of neurons that correspond to the lateral and medial mammillary body neurons they found in mice.

Similar to the mouse studies, the researchers also found signatures of hyperactivity in the lateral mammillary bodies from Alzheimer’s tissue samples, including overexpression of genes that encode potassium and sodium channels. In those samples, they also found higher levels of neurodegeneration in the lateral neuron cluster, compared to the medial cluster.

Other studies of Alzheimer’s patients have found a loss of volume of the mammillary body early in the disease, along with deposition of plaques and altered synaptic structure. All of these findings suggest that the mammillary body could make a good target for potential drugs that could slow down the progression of Alzheimer’s disease, the researchers say.

Tsai’s lab is now working on further defining how the lateral neurons of the mammillary body are connected to other parts of the brain, to figure out how it forms memory circuits. The researchers also hope to learn more about what properties of the lateral neurons of the mammillary body make them more vulnerable to neurodegeneration and amyloid deposition.

The research was funded by the JBP Foundation, the Ludwig Family Foundation, and the U.S. National Institutes of Health.

It’s a result that has been decades in the making. The dataset was originally collected in 2004. Lamiaa El Fassi, now an associate professor of physics at Mississippi State University and principal investigator of the work, first analyzed these data during her thesis project to earn her graduate degree on a different topic.

Nearly a decade after completing her initial research with these data, El Fassi revisited the dataset and led her group through a careful analysis to yield these unprecedented measurements. The dataset comes from experiments in Jefferson Lab’s Continuous Electron Beam Accelerator Facility (CEBAF), a DOE user facility. In the experiment, nuclear physicists tracked what happened when electrons from CEBAF scatter off the target nucleus and probe the confined quarks inside protons and neutrons. The results were recently published in Physical Review Letters.

“These studies help build a story, analogous to a motion picture, of how the struck quark turns into hadrons. In a new paper, we report first-ever observations of such a study for the lambda baryon in the forward and backward fragmentation regions,” El Fassi said.

In like a lambda, out like a pion

Like the more familiar protons and neutrons, each lambda is made up of three quarks.

Unlike protons and neutrons, which only contain a mixture of up and down quarks, lambdas contain one up quark, one down quark and one strange quark. Physicists have dubbed matter that contains strange quarks “strange matter.”

In this work, El Fassi and her colleagues studied how these particles of strange matter form from collisions of ordinary matter. To do so, they shot CEBAF’s electron beam at different targets, including carbon, iron, and lead. When a high-energy electron from CEBAF reaches one of these targets, it breaks apart a proton or neutron inside one of the target’s nuclei.

“Because the proton or neutron is totally broken apart, there is little doubt that the electron interacts with the quark inside,” El Fassi said.

After the electron interacts with a quark or quarks via an exchanged virtual photon, the “struck” quark(s) begins moving as a free particle in the medium, typically joining up with other quark(s) it encounters to form a new composite particle as they propagate through the nucleus. And some of the time, this composite particle will be a lambda.

But the lambda is short-lived — after formation, it will swiftly decay into two other particles: a pion and either a proton or neutron. To measure different properties of these briefly created lambda particles, physicists must detect its two daughter particles, as well as the beam electron that scattered off the target nucleus.

The experiment that collected this data, EG2, used the CEBAF Large Acceptance Spectrometer (CLAS) detector in Jefferson Lab’s Experimental Hall B. These recently published results, “First Measurement of ? Electroproduction off Nuclei in the Current and Target Fragmentation Regions,” are part of the CLAS collaboration, which involves almost 200 physicists worldwide.

SIDIS

This work is the first to measure the lambda using this process, which is known as semi-inclusive deep inelastic scattering, in the forward and backward fragmentation regions. It’s more difficult to use this method to study lambda particles, because the particle decays so quickly, it can’t be measured directly.

“This class of measurement has only been performed on protons before, and on lighter, more stable particles,” said coauthor William Brooks, professor of physics at Federico Santa María Technical University and co-spokesperson of the EG2 experiment.

The analysis was so challenging, it took several years for El Fassi and her group to re-analyze the data and extract these results. It was her thesis advisor, Kawtar Hafidi, who encouraged her to pursue the investigation of the lambda from these datasets.

“I would like to commend Lamiaa’s hard work and perseverance in dedicating years of her career working on this,” said Hafidi, associate laboratory director for physical sciences and engineering at Argonne National Lab and co-spokesperson of the EG2 experiment. “Without her, this work would not have seen fruition.”

“It hasn’t been easy,” El Fassi said. “It’s a long and time-consuming process, but it was worth the effort. When you spend so many years working on something, it feels good to see it published.”

El Fassi began this lambda analysis when she herself was a postdoc, a couple of years prior to becoming an assistant professor at Mississippi State University. Along the way, several of her own postdocs at Mississippi State have helped extract these results, including coauthor Taya Chetry.

“I’m very happy and motivated to see this work being published,” said Chetry, who is now a postdoctoral researcher at Florida International University.

Two for one

A notable finding from this intensive analysis changes the way physicists understand how lambdas form in the wake of particle collisions.

In similar studies that have used semi-inclusive deep inelastic scattering to study other particles, the particles of interest usually form after a single quark was “struck” by the virtual photon exchanged between the electron beam and the target nucleus. But the signal left by lambda in the CLAS detector suggests a more packaged deal.

The authors’ analysis showed that when forming a lambda, the virtual photonhas been absorbed part of the time by a pair of quarks, known as a diquark, instead of just one. After being “struck,” this diquark went on to find a strange quark and forms a lambda.

“This quark pairing suggests a different mechanism of production and interaction than the case of the single quark interaction,” Hafidi said.

A better understanding of how different particles form helps physicists in their effort to decipher the strong interaction, the fundamental force that holds these quark-containing particles together. The dynamics of this interaction are very complicated, and so is the theory used to describe it: quantum chromodynamics (QCD).

Comparing measurements to models of QCD’s predictions allows physicists to test this theory. Because the diquark finding differs from the model’s current predictions, it suggests something about the model is off.

“There is an unknown ingredient that we don’t understand. This is extremely surprising, since the existing theory can describe essentially all other observations, but not this one,” Brooks said. “That means there is something new to learn, and at the moment, we have no clue what it could be.”

To find out, they’ll need even more measurements.

Data for EG2 were collected with 5.014 GeV (billion electron-volt) electron beams in the CEBAF’s 6 GeV era. Future experiments will use electron beams from the updated CEBAF, which now extend up to 11 GeV for Experimental Hall B, as well as an updated CLAS detector known as CLAS12, to continue studying the formation of a variety of particles, including lambdas, with higher-energy electrons.

The upcoming Electron-Ion Collider (EIC) at DOE’s Brookhaven National Laboratory will also provide a new opportunity to continue studying this strange matter and quark pairing structure of the nucleon with greater precision.

“These results lay the groundwork for upcoming studies at the upcoming CLAS12 and the planned EIC experiments, where one can investigate the diquark scattering in greater detail,” Chetry said.

El Fassi is also a co-spokesperson for CLAS12 measurements of quark propagation and hadron formation. When data from the new experiments is finally ready, physicists will compare it to QCD predictions to further refine this theory.

“Any new measurement that will give novel information toward understanding the dynamics of strong interactions is very important,” she said.