In a new Northwestern Medicine study, scientists sought to better understand how humans evolved to become so skilled at thinking about what’s happening in other peoples’ minds. The findings could have implications for one day treating psychiatric conditions such as anxiety and depression.

“We spend a lot of time wondering, ‘What is that person feeling, thinking? Did I say something to upset them?'” said senior author Rodrigo Braga. “The parts of the brain that allow us to do this are in regions of the human brain that have expanded recently in our evolution, and that implies that it’s a recently developed process. In essence, you’re putting yourself in someone else’s mind and making inferences about what that person is thinking when you cannot really know.”

The study found the more recently evolved and advanced parts of the human brain that support social interactions — called the social cognitive network — are connected to and in constant communication with an ancient part of the brain called the amygdala.

Often referred to as our “lizard brain,” the amygdala typically is associated with detecting threats and processing fear. A classic example of the amygdala in action is someone’s physiological and emotional response to seeing a snake: startled body, racing heart, sweaty palms. But the amygdala also does other things, Braga said.

“For instance, the amygdala is responsible for social behaviors like parenting, mating, aggression and the navigation of social-dominance hierarchies,” said Braga, an assistant professor of neurology at Northwestern University Feinberg School of Medicine. “Previous studies have found co-activation of the amygdala and social cognitive network, but our study is novel because it shows the communication is always happening.”

The study was published Nov. 22 in the journal Science Advances.

High-resolution brain scans were key

Within the amygdala, there’s a specific part called the medial nucleus that is very important for social behaviors. This study was the first to show the amygdala’s medial nucleus is connected to newly evolved social cognitive network regions, which are involved in thinking about other people. This link to the amygdala helps shape the function of the social cognitive network by giving it access to the amygdala’s role in processing emotionally important content.

This was only possible because of functional magnetic resonance imaging (fMRI), a noninvasive brain-imaging technique that measures brain activity by detecting changes in blood oxygen levels. A collaborator at the University of Minnesota and co-author on the study, Kendrick Kay, provided Braga and co-corresponding author Donnisa Edmonds with fMRI data from six study participants’ brains, as part of the Natural Scenes Dataset (NSD). These high-resolution scans enabled the scientists to see details of the social cognitive network that had never been detected on lower-resolution brain scans. What’s more, they were able to replicate the findings up to two times in each individual.

“One of the most exciting things is we were able to identify network regions we weren’t able to see before,” said Edmonds, a neuroscience Ph.D. candidate in Braga’s lab at Northwestern. “That’s something that had been underappreciated before our study, and we were able to get at that because we had such high-resolution data.”

Potential treatment of anxiety, depression

Both anxiety and depression involve amygdala hyperactivity, which can contribute to excessive emotional responses and impaired emotional regulation, Edmonds said. Currently, someone with either condition could receive deep brain stimulation for treatment, but since the amygdala is located deep within the brain, directly behind the eyes, it means having an invasive, surgical procedure. Now, with this study’s findings, a much less-invasive procedure, transcranial magnetic stimulation (TMS), might be able to use knowledge about this brain connection to improve treatment, the authors said.

“Through this knowledge that the amygdala is connected to other brain regions — potentially some that are closer to the skull, which is an easier region to target — that means people who do TMS could target the amygdala instead by targeting these other regions,” Edmonds said.

The study is titled, “The human social cognitive network contains multiple regions within the amygdala.” Other Northwestern co-authors include Christina Zelano, Joseph J. Salvo, Nathan Anderson, Maya Lakshman and Qiaohan Yang.

The study highlights significant racial and socioeconomic disparities, finding that non-Hispanic Black mothers faced more than double the rate of severe complications compared to non-Hispanic white mothers, and that living in high-poverty neighborhoods elevated maternal health risks across all racial groups.

“Despite significant recent statewide quality-improvement efforts, these birth outcomes are worsening for all ages, reflecting the worsening pre-pregnancy health of the reproductive-age population in Illinois,” said corresponding author Dr. Mugdha Mokashi, aresident physician in obstetrics and gynecology at the McGaw Medical Center at Northwestern.

The findings reflect national trends demonstrating the increasing prevalence of conditions such as obesity, hypertensive disorders of pregnancy and gestational diabetes among pregnant people of all ages, she added. The study provides the most updated data on maternal morbidity and delivery complications within the state of Illinois.

The findings were published Nov. 21 in the journal Obstetrics & Gynecology Open.

“Our findings underscore the role of social determinants of health — such as race and income — in driving disparities in maternal health, suggesting that efforts to reduce maternal morbidity need to address both racial inequalities and economic hardship,” said study co-author Dr. Lynn Yee, associate professor of obstetrics and pulmonology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine maternal fetal medicine physician.

Breaking down of the findings:

In the study cohort of 988,480 births at 127 Illinois hospitals between January 2016 to June 2023, the overall rate of severe maternal morbidity rose from 1.4% in 2016 to 2% in 2023. Vaginal birth complications increased 22.4%, and cesarean birth complications increased 48.9%.

Hypertensive disorders of pregnancy and anemia — both of which increased over the study period — were significant risk factors for severe maternal morbidity and birth complications. The largest increase by far was in annual rates of obesity from 2016 to the first six months of 2023 (7.8% to 22.3%). Additionally, there were increases in gestational diabetes (4.2% to 5.5%), depression (2.5% to 6.6%), anxiety (3.1% to 10.4%) and other chronic comorbidities (4.7% to 7.4%). Non-Hispanic Black patients had more than double the severe maternal morbidity rate (2.6%) compared to non-Hispanic white patients (1.1%).

Health counseling before pregnancy is important

Maternal health affects almost everyone, and those thinking about pregnancy should be sure to check in with their health care provider to screen for any chronic conditions they may have before getting pregnant, the study authors said.

“Pre-conception counseling is such an important way to make sure that all of your health conditions are optimized prior to pregnancy,” Mokashi said. “There are many important policy and public health initiatives in Illinois that people may be interested in learning more about.”

‘It’s not just because the people getting pregnant are older’

While not the original aim of the study, the scientists did additional analysis that found the increased prevalence of maternal health issues and birth complications is not simply because the people getting pregnant are older. The findings reflected an increase in hospital coding for hypertensive disorders of pregnancy, gestational diabetes, anemia, depression, serious mental illness and other chronic conditions, especially obesity, even among those giving birth who are younger than 30.

“In brief, even young pregnant patients have more medical conditions and complications in pregnancy,” Mokashi said.

What can be done?

Policies for poverty alleviation — such as the proposed refundable child tax credit in Illinois, House Bill 4917, if passed — have demonstrated improvement in maternal health, the study authors said.

Perinatal quality initiatives in California have reduced postpartum hemorrhage-related morbidity. Similarly, the Illinois Perinatal Quality Collaborative is working to reduce cesarean births and address racial disparities through Promoting Vaginal Birth and Birth Equity initiatives.

Increasing access to doula support and patient navigator programs could also be useful supports, Mokashi said. In 2024, the Illinois Department of Healthcare and Family Services adjusted reimbursement for doula services. At Northwestern, research on patient-navigator programs have shown promise in reducing care disparities for low-income minoritized patients postpartum. And at the federal level, passage of the 13 bills comprising the Black Maternal Health Momnibus Act re-introduced in 2023 would provide critical funding support to increase data collection and quality initiatives for prevention of maternal morbidity.

It’s a core function, but little studied in the setting of cancer immunology, especially when compared to other organelles like the mitochondria or endoplasmic reticulum.

“So we were interested in looking a little bit more at the Golgi apparatus. It’s obviously an important organelle. How is it being changed or what is its role in T-cells in terms of fighting cancer?” said Nathaniel Oberholtzer, an M.D./Ph.D. student who worked in the lab of Shikhar Mehrotra, Ph.D., co-leader of the Cancer Biology & Immunology Research Program at MUSC Hollings Cancer Center and scientific director of the Center for Cellular Therapy in the MUSC College of Medicine.

As it turns out, the healthy function of the Golgi apparatus has a lot to do with how well T-cells function in killing cancer cells. Understanding how a signaling axis mitigates Golgi stress, enabling it to perform properly, points to a possible new therapeutic target for researchers to pursue to strengthen T-cells. Not only that, but Oberholtzer’s research shows how the Golgi could be used as a biomarker to select the strongest T-cells for immunotherapy.

Oberholtzer, as first author, and Mehrotra, as senior author, along with a team of Hollings scientists published the research this month in Science Advances.

T-cells, part of the immune system, can kill cancer cells. CAR-T cells are T-cells that have been modified in the lab to home in on proteins on the surface of an individual’s cancer cells. CAR-T cells are custom-made for each patient.

Both T-cells and CAR-T cells can become “exhausted” in the hostile tumor microenvironment. Mehrotra’s lab looks at ways to boost these cells so that they can fight cancer for a longer time.

“The whole tumor microenvironment is conducive for the tumor itself, but not for the other cells which are trying to get in there,” Mehrotra said.

Just like people, cells are constantly subjected to stress — stress from biochemical reactions that have become unbalanced and mechanical stress from moving. Transient stress can be good. Stressing your muscles through exercise strengthens them, and transient stress on cells can prompt them to a response that ultimately strengthens them.

“But if this stress stays there, which it does in the tumor microenvironment, the cells are just in continuous stress, and that will then lead to a very different phenotype and death,” Mehrotra said.

However, the researchers found that treating the Golgi apparatus with hydrogen sulfide created T-cells that could take more stress.

“Hydrogen sulfide is a gaseous signaling molecule present in pretty much all mammalian cell types. Typically, it’s a byproduct of different cellular processes, but it’s actually been shown to have really important signaling roles as well,” Oberholtzer said.

“It can modify proteins through a process called sulfhydration, where it modifies cysteine residues and can change their activity.”

In this project, Oberholtzer found that this sulfhydration process, in modifying a protein called Prdx4 within the Golgi apparatus, confers protection in an oxidative setting.

“When you have the stressors that the tumor microenvironment puts on T-cells, you get a disruption, or fragmentation, of the Golgi apparatus where it essentially isn’t able to do its job. Hydrogen sulfide protects against that disruption,” Oberholtzer said.

Looking into this protective effect then led the researchers to look more closely at the Golgi apparatus by itself.

“Essentially, if you just use the Golgi apparatus as a simple marker, if T-cells have a lot of Golgi versus less, the ones that have more Golgi are much more robust at killing tumor cells and controlling tumors,” Oberholtzer explained.

Using cell sorting technology at the Flow Cytometry & Cell Sorting Shared Resource at Hollings, the researchers sorted T-cells according to the amount of Golgi they contained. The top 30% were labeled Golgi-hi and the bottom 30% were labeled Golgi-lo.

“Basically, all the cells which are expressing high Golgi have a very different phenotype. They are less exhausted, and they are much more potent in controlling tumors,” Mehrotra said.

This pre-clinical work suggests that sorting T-cells into Golgi-hi and Golgi-lo and reinfusing only the Golgi-hi cells into a patient would create a better chance of controlling the tumor.

“Right now, we’re working on doing some validation studies in the Center for Cellular Therapy to potentially be able to start a clinical trial to see if that has a translational ability as well,” Oberholtzer said.

More work is also needed to understand the role of Golgi stress when all of the organelles in a cell are under stress because of the tumor microenvironment.

Escalating resistance by these mutants forces farmers and vector control specialists to ramp up use of poisonous compounds at increasing frequencies and concentrations, posing risks to human health and damage to the environment since most insecticides kill both ecologically important insects as well as pests.

To help counter these problems, researchers recently developed powerful technologies that genetically remove insecticide-resistant variant genes and replace them with genes that are susceptible to pesticides. These gene-drive technologies, based on CRISPR gene editing, have the potential to protect valuable crops and vastly reduce the amount of chemical pesticides required to eliminate pests.

Still, gene-drive systems have come under scrutiny with concerns that once they are released into a population they could continuously spread unchecked.

University of California San Diego geneticists have now developed a solution to this concern. Publishing in the journal Nature Communications, School of Biological Sciences Postdoctoral Scholar Ankush Auradkar and Professor Ethan Bier led the creation of a new genetic system that converts insecticide-resistant forms of mutated insect genes back to their natural, native form. The novel system is designed to spread the original “wild type” version of the gene using the biased inheritance of specific genetic variants known as alleles and then disappear, leaving only a population of insects with the corrected version of the gene.

“We have developed an efficient biological approach to reverse insecticide resistance without creating any other perturbation to the environment,” said Bier, a professor in the Department of Cell and Developmental Biology, of the self-eliminating allelic drive, or “e-Drive.” “The e-Drive is programmed to act transiently and then disappear from the population.”

As described in the paper, the researchers created a novel genetic “cassette,” a small group of DNA elements, and inserted it inside fruit flies as a proof-of-concept technology that could be applied to other insects. They developed the e-Drive to target a gene known as the voltage gated sodium ion channel, or vgsc, which is required for proper nervous system functioning.

The e-Drive cassette is designed to spread through CRISPR gene editing and features a guide RNA that binds to a Cas9 DNA protein and makes a cut at the targeted vgsc insecticide resistant gene site. The gene is then switched out for a native copy of the gene that is susceptible to insecticides.

Per the study, when insects carrying the cassette are introduced into a target population, they mate randomly and transmit the e-Drive cassette to their offspring. To maintain control of the e-Drive’s spread, the researchers imposed a fitness check on those carrying the cassette, either through limited viability or fertility. The cassette was inserted on the X-chromosome and reduced the mating success of males, resulting in reduced offspring. The frequency of the cassette in the population eventually declines through each generation until it fully vanishes from the population.

In laboratory experiments all of the offspring were converted to native genes in eight-to-10 generations, which took about six months in flies.

“Because insects carrying the gene cassette are penalized with a severe fitness cost, the element is rapidly eliminated from the population, lasting only as long as it takes to convert 100 percent of the insecticide-resistant forms of the target gene back to wild-type,” said Auradkar.

The researchers note that the self-eliminating nature of the e-Drive means it can be introduced and re-introduced as needed, and as different types of pesticides are used. The researchers are now developing a similar e-Drive system in mosquitoes to help prevent the spread of malaria.

In addition to Auradkar and Bier, the coauthors of the Nature Communications paper included their close collaborators Rodrigo Corder of the Institute of Biomedical Science, University of SãoPaulo; and John Marshall of the Innovative Genomics Institute, who performed sophisticated mathematical modeling that revealed important hidden features of the e-Drive system, including its ability to efficiently cull a class of individuals in which the drive process did not occur.

Led by Lianyi Chen, an associate professor of mechanical engineering at UW-Madison, the team discovered the mechanisms and identified the processing conditions that can lead to this significant reduction in defects. The researchers detailed their findings in a paper published on November 16, 2024, in the International Journal of Machine Tools and Manufacture.

“Previous research has normally focused on reducing one type of defect, but that would require the usage of other techniques to mitigate the remaining types of defects,” Chen says. “Based on the mechanisms we discovered, we developed an approach that can mitigate all the defects — pores, rough surfaces and large spatters — at once. In addition, our approach allows us to produce a part much faster without any quality compromises.”

Multiple industries, including aerospace, medical and energy, are increasingly interested in using additive manufacturing, also known as 3D printing, to produce metal parts with complex shapes that are difficult or impossible to create using conventional methods.

But the big challenge is that metal parts created with additive manufacturing have defects — like pores, or “voids,” rough surfaces and large spatters — that significantly compromise the finished part’s reliability and durability. These quality problems prevent 3D-printed parts from being used for critical applications where failure is not an option.

By providing a path for simultaneously increasing part quality and manufacturing productivity, the UW-Madison team’s advance could lead to widespread industry adoption of laser powder bed fusion.

Laser powder bed fusion uses a high-energy laser beam to melt and fuse thin layers of metal powder, constructing a part layer by layer from the bottom up. In this research, the UW-Madison team used an innovative ring-shaped laser beam, provided by a leading laser company called nLight, instead of the usual Gaussian-shaped beam.

The ring-shaped laser beam played a key role in this breakthrough — as did critical “in-situ” experiments, says Jiandong Yuan, the lead author of the paper and a PhD student in Chen’s group.

To see how the material behaved within the part as it was printing, researchers went to the Advanced Photon Source, an ultra-bright, high-energy synchrotron X-ray user facility at Argonne National Laboratory. Combining high-speed synchrotron X-ray imaging, theoretical analysis and numerical simulation, the researchers revealed the defect mitigation mechanisms, which involve phenomena that reduce instabilities in the laser powder bed fusion process.

The researchers also demonstrated that they could use the ring-shaped beam to drill deeper into the material without causing instabilities in the process. This enabled them to print thicker layers, increasing the manufacturing productivity. “Because we understood the underlying mechanisms, we could more quickly identify the right processing conditions to produce high-quality parts using the ring-shaped beam,” says Chen.

Lianyi Chen is the Kuo K. & Cindy F. Wang Associate Professor of mechanical engineering.

Collaborators from UW-Madison include Qilin Guo, Luis Escano, Ali Nabba, Minglei Qu, Junye Huang, Qingyuan Li, Allen Jonathan Román, and Professor Tim Osswald. Samuel Clark and Kamel Fezzaa from Argonne National Laboratory also collaborated on this project.

This work was supported by the National Science Foundation and the Wisconsin Alumni Research Foundation.

The study, published in Nature Communications, shows that Indigenous political and social networks and land use practices played key roles in the peach’s adoption and dispersal across the continent, according to the researchers.

“Peaches need a lot of care by people to be productive. They need to be planted in appropriate places with a lot of sunlight and the right soil drainage, and they need to be pruned,” said Jacob Holland-Lulewicz, first author and assistant professor of anthropology at Penn State. “For a long time, the narrative was that the Spanish introduced peaches and then peaches spread very quickly. The reality is way more complicated. How quickly peaches spread is very much a product of Indigenous networks and land management.”

The researchers analyzed historical documents that mentioned peaches, such as the travel writings of French missionary explorer Jacques Marquette and English merchant Jonathan Dickinson. They also employed radiocarbon dating — a method that measures the decay of radioactive carbon-14 atoms in organic material — to determine the approximate ages of peach pits and other organic samples, like carbonized tree wood, from 28 archaeological sites and two regional locales where archaeologists previously recovered preserved peach pits. The sites were located in the Carolinas, Georgia, Florida, Alabama, Tennessee and Arkansas.

The team found that peaches were likely widespread across Indigenous settlements in the interior southeast as early as the year 1620, roughly 100 years after the earliest Spanish expeditions in Florida and in Georgia’s Oconee Valley. The timing suggests that early Spanish settlements becoming important trade nodes within existing Indigenous networks created the necessary conditions for the spread of peaches, according to Holland-Lulewicz.

“Many narratives talk about the Spanish, or Europeans generally, arriving and then you see instantaneous changes to Indigenous histories and the spread of materials, but those initial interactions didn’t cause major changes,” he said. “It’s not until Spanish networks and Indigenous networks become entangled 100 years later that we have the necessary conditions for the spread of peaches.”

The team also identified what are possibly the earliest peaches in North America at a Muskogean farmstead in the Oconee Valley. In the 1990s, the late Penn State archaeologist James Hatch recovered peach pits from the bottom of post holes that once housed support structures for the farmstead’s house. The researchers radiocarbon dated charcoal, nuts and corn kernels from these post holes and found that occupation at the site began between 1520 and 1550 and ended between 1530 and 1570. This timing suggests that peaches had spread to the interior southeast possibly decades before the founding of St. Augustine in 1565, according to the researchers.

“Understanding the path that the introduction of species, such as peach trees, took through colonization and the role that Indigenous people and their long-term relationship with the environment played in shaping these histories demonstrates the importance of these events, people and processes to what becomes a broader American history,” said co-author Victor Thompson, Distinguished Research Professor of archaeology at the University of Georgia (UGA) and executive director of the Georgia Museum of Natural History. “Further, the fact that all of this work took place on museum specimens underscores the importance of maintaining these collections for future study.”

Indigenous peoples not only adopted the peach but selectively bred new varieties outnumbering the varieties found in Europe even at this early time, Holland-Lulewicz said.

“When Europeans started to move through and into the interior of the continent in the mid- to late 1600s, they noted that there were way more varieties of peaches being grown by Indigenous peoples than there were in Europe,” he said, explaining that the fruit had become an important aspect of Indigenous culture. “At this time, Europeans are noting really dense peach orchards around Indigenous towns, but some of these towns and people had never previously interacted with or even heard of Europeans. In fact, there are records of Indigenous peoples describing peaches as an Indigenous fruit.”

The fruit had become so integral to Indigenous history and culture that when the ancestors of the modern-day Muscogee (Creek) Nation were forcibly removed from Georgia and Alabama during the 1800s, they took peaches with them.

“There are Muscogee (Creek) peoples today who grow peaches as heritage crops,” Holland-Lulewicz said. “The act of growing and caring for those peaches is an important cultural practice. These were the first peaches introduced in the 1500s and 1600s that were then carried halfway across the continent and continue to be grown today.”

In addition to Holland-Lulewicz and Thompson, other collaborators include Amanda Roberts Thompson and Mark Williams at the UGA Laboratory of Archaeology, and Dario J. Chavez, University of Georgia; RaeLynn Butler, the Secretary of Culture and Humanities for the Muscogee (Creek) Nation, and Turner Hunt, Muscogee (Creek) Nation citizen; Jay Franklin, Logan Simpson Design; and John Worth, University of West Florida.

The UGA Laboratory of Archaeology and the Institute of Energy and the Environment at Penn State supported this work.