Culture

UPTON, NY--What happens when very short pulses of laser light strike a magnetic material? A large international collaboration led by the U.S. Department of Energy's (DOE) Brookhaven National Laboratory set out to answer this very question. As they just reported in the Proceedings of the National Academy of Sciences, the laser suppressed magnetic order across the entire material for several picoseconds, or trillionths of a second. Understanding how magnetic correlations change on ultrafast timescales is the first step in being able to control magnetism in application-oriented ways. For example, with such control, we may be able to more quickly write data to memory devices or enhance superconductivity (the phenomenon in which a material conducts electricity without energy loss), which often competes with other states like magnetism.

The material studied was strontium iridium oxide (Sr3Ir2O7), an antiferromagnet with a bilayer crystal structure and a large magnetic anisotropy. In an antiferromagnet, the magnetic moments, or electron spins, align in opposite directions to neighboring spins. Anisotropy means the spins need to pay an energetic cost to rotate in any random direction; they really want to sit pointing upwards or downwards in the crystal structure. The X-ray Scattering Group of Brookhaven Lab's Condensed Matter Physics and Materials Science (CMPMS) Division has previously studied this material (and a single-layer sister compound, Sr2IrO4), so they entered this study with a good understanding of its equilibrium state.

"The very short laser pulses disturb the system, destroying its magnetic order," said first author Daniel Mazzone, former group member and now an instrument scientist at the Continuous Angle Multiple Energy Analysis (CAMEA) spectrometer at the Paul Scherrer Institute in Switzerland. "In this study, we were interested in seeing how the system relaxes back to its normal state. We knew the relaxation occurs on a very fast timescale, and to take a picture of something that moves very fast, we need very short pulses of illumination. With an x-ray free-electron laser source, we can generate pulses short enough to see the movement of atoms and molecules. Such sources only exist at five places around the world--in the United States, Japan, Korea, Germany, and Switzerland."

In this study, the team ran experiments at two of the five facilities. At the SPring-8 Angstrom Compact free-electron Laser (SACLA) in Japan, they conducted time-resolved resonant elastic x-ray scattering (tr-REXS). At the x-ray pump-probe instrument of the Linac Coherent Light Source--a DOE Office of Science User Facility at SLAC National Accelerator Laboratory--the scientists performed time-resolved resonant inelastic x-ray scattering (tr-RIXS). In both scattering techniques, x-rays (probe) strike the material almost immediately after the laser pulse (pump). By measuring the energy and angle of scattered particles of light (photons), scientists can determine the material's electronic structure and thus magnetic configuration. In this case, the x-ray energy was tuned to be sensitive to the electrons around iridium atoms, which drive magnetism in this material. While tr-REXS can reveal the degree of long-range magnetic order, tr-RIXS can provide a picture of local magnetic interactions.

"In order to observe the detailed behavior of spins, we need to measure the energy change of the x-rays with very high precision," explained co-corresponding author Mark Dean, a physicist in the CMPMS Division X-ray Scattering Group. "To do so, we built and installed a motorized x-ray spectrometer at SLAC."

Their data revealed how magnetic interactions are suppressed not just locally but everywhere. This suppression persists for picoseconds before the magnetic order returns to its initial antiferromagnetic state.

"The bilayer system does not have energetically low-cost ways to deform the magnetic state," explained Dean. "It gets stuck in this bottleneck where the magnetism is out of equilibrium and is not recovering, at least not as quickly as in the monolayer system."

"For most applications, such as data storage, you want fast magnetic switching," added Mazzone. "Our research suggests systems where spins can point whichever direction are better for manipulating magnetism."

Next, the team plans to look at related materials and hopes to manipulate magnetism in more targeted ways--for example, changing how strongly two neighboring spins "talk to" each other.

"If we can change the distance between two spins and see how that affects their interaction, that would be really cool," said Mazzone. "With an understanding of how magnetism evolves, we could tweak it, maybe generating new states."

The ability of stem cells to fix impaired functions of host tissues after transplantation has been a lifesaving breakthrough in treating previously incurable conditions. Much like a coin toss, however, the fate of the transplanted stem cells is unpredictable. They may choose self-renewal, grow into a different kind of tissue, or die.

Spermatogonial stem cells follow the same stochastic fate of unpredictability in outcomes. But a group of fertility scientists led by Hiroshima University's Yoshiaki Nakamura discovered a new method that has favorably flipped the odds and successfully reversed male infertility in mice -- showing great promise for future applications in regenerating human sperm after cancer treatment and repopulating threatened and endangered species. Results of their study are published in the journal Cell Stem Cell.

"Transplantation of spermatogonial stem cells promises a wealth of applications such as the treatment of infertility in men and the preservation of genetic diversity. Yet, currently, its inefficiency rules out the practical application of this technology," Nakamura, assistant professor at the HU Graduate School of Integrated Sciences for Life, said.

"Our knowledge about the fate behavior of individual spermatogonial stem cells and their progenies following transplantation remains poorly developed, limiting the potential to develop new strategies to increase the currently low transplantation efficiencies," he added.

Taking an up-close look at single-cell resolution, the international team of Japanese and British scientists tracked the fate of transplanted spermatogonial stem cells in mice. They implanted normal mouse sperm stem cells in infertile mice and found that only a tiny fraction repopulates in the long-term as working spermatogonia and the rest change into a different type of cell -- a process called differentiation -- or cease to carry out its function and die.

Using these insights, they developed a new method that can artificially tune the fate of the sperm stem cells to increase the likelihood of repopulation to a level where fertility is restored. They briefly introduced a retinoic acid synthesis inhibitor after transplantation, which temporarily prevented the donor sperm stem cells from undergoing differentiation. The chemical inhibitor helped orchestrate an outcome where the stem cells choose a fate of self-renewal.

"We demonstrated that repopulation efficiency of transplanted spermatogonial stem cells increased by tuning their stochastic fate," Nakamura said, adding that the next step for their research is to confirm if their new strategy will also work for livestock and eventually humans.

"My final objective is to apply spermatogonial stem cell transplantation for the fertility of male individuals with cancer after chemotherapy or the preservation of genetic diversity in farm animals and rare or endangered wild animals," he said.

Normally, the ACE2 enzyme helps regulate our blood pressure. The enzyme sits on the surface of cells, including cells in the lungs, but in connection with COVID-19 it has been found that ACE2 also functions as a gateway for the virus.

"Different viruses have different ways of accessing our cells - as the virus must, of course, get into the cell to be able to replicate, and the coronavirus uses ACE2 to gain access. For this reason, we're investigating what the concentration of ACE2 means for the course of the disease, if you get COVID-19," explains MD and PhD Tue Wenzel Kragstrup from the Department of Biomedicine at Aarhus University. The preliminary results have just been published in the scientific journal PLOS ONE.

As mentioned, ACE2 is part of the surface of the cells, but ACE2 can also be chopped off and found in the blood, and measurements show that we have widely varying concentrations in our blood.

With the help of comprehensive data from patients treated at Massachusetts General Hospital, Tue Wenzel Kragstrup and his colleagues attempt to uncover whether the concentration of ACE2 can perhaps be used as a biomarker to predict the risk of dying as a result of COVID-19.

"This is the pivotal question," says Tue Wenzel Kragstrup, although he also acknowledges that it cannot yet be answered, among other things, because we currently lack an easily accessible and applicable test for ACE2.

However, this is not the case for another enzyme, ACE1. Here, there is a standard and routinely used test for when doctors e.g. need to diagnose the pulmonary disease sarcoidosis.

"We know that there is a correlation between ACE1 and ACE2," says Tue Wenzel Kragstrup. "If our findings can be recreated by measuring ACE1, this can be used in the clinical work right away."

Tue Wenzel Kragstrup's normal area of research is biomarkers and rheumatological diseases, but when everything closed down due to the COVID-19 pandemic, he felt obliged to use his knowledge of biomarkers in particular and, in this way, join the fight against the new disease.

"I discovered that Massachusetts General Hospital in Boston, USA, had published a huge amount of data and analyses on their website of 306 patients with COVID-19, together with data and analyses from 78 patients who had tested negative for COVID-19. The information is encrypted so that it's not possible to identify individuals, but the cohort of patients were followed for 28 days, so you can see what happened to them," says Tue Wenzel Kragstrup, who is fascinated by the international collaboration in the fight against COVID-19.

He retrieved the dataset in the form of a "really huge spreadsheet" and then, with the help of biostatisticians and other experts, began analysing the vast amount of data - and it was here that he became aware of the important role ACE2 appears to play.

"We're familiar with a heightened concentration of ACE2 in connection with cardiovascular diseases, but the concentration is not, for example, higher in connection with diabetes, which we can also see in our study. But we now hope that ACE2 can help explain excess mortality from COVID-19," says Tue Wenzel Kragstrup.

AUSTIN, Texas -- Puerto Rico is not ready for another hurricane season, let alone the effects of climate change, according to a new study that shows the island's outstanding capacity to produce record-breaking floods and trigger a large number of landslides.

The latest research, appearing in the journal Hydrology, builds on three prior studies led by hydrologist Carlos Ramos-Scharrón at The University of Texas at Austin, whose team began investigating the devastating impact of tropical cyclones on the island after Hurricane Maria in 2017.

The first compared the 2017 hurricane as a rainstorm event to more than a century of cyclones that came before it, finding that Maria produced the highest island-wide daily rainfall amount ever recorded (similar to Hurricane Harvey's impact on Houston). The second found that Maria's rainfall triggered one of the highest number of rainfall-induced landslides ever reported worldwide in similarly sized areas. And the third identified landslides as the main source of the sediment infilling the already limited water storage capacity of the island's main reservoirs.

"We need to stop talking about climate change in future tense. It's already here," said Ramos-Scharrón, associate professor in the Department of Geography and the Environment and the Teresa Lozano Long Institute of Latin American Studies. "Climate change projections for the Caribbean suggest longer dry periods interrupted by more intense storms. These storms release large quantities of sediment by landslides, and many of those end up reducing the island's capacity to store water. The combined effect of these climate change projections is for a higher propensity for water scarcity."

The latest paper, which focused on streamflow levels, draws attention to another glaring issue -- Puerto Rico is not prepared to handle the severe flooding sure to come its way. Flood management and the design of vital infrastructure, such as bridges, largely rely on a calculation of the likelihood that an event of a given magnitude is going to occur. For a particular region, that calculation depends on the history of flooding.

In Puerto Rico, the most current method to make such calculations relies on data collected only up to 1994. Since then, Hurricanes Hortense (1996), Georges (1998) and Maria surpassed both 100-year and 500-year flood marks across the island, with Maria surpassing 500-year levels in five locations.

Five other tropical storms matched or surpassed 100- and 500-year levels in some specific locations, particularly near the central-eastern end of Puerto Rico, which is most vulnerable due to the westward trajectory of most tropical cyclones and the island's hilly topography.

"Events with these 100- and 500-year metrics just cannot be that common," Ramos-Scharrón said. "If this is not what climate change is supposed to be, then I do not know what it is. It can creep up on you. Puerto Rico needs to adapt its planning tools to the reality of what the island has experienced and scientists are documenting."

A study examining gender bias and family-owned businesses found daughters were rarely encouraged nor received support to pursue entrepreneurship education while sons mostly did.

Professors James Combs, Peter Jaskiewicz, and Sabine Raul from the Telfer School of Management uncovered new insights about how gender bias - the preference of a gender over the other - affects the succession strategy in multi-generational family firms. Their findings are published in the Journal of Small Business Management.

When nurturing the next generation, entrepreneurial families often prepare their daughters and sons differently for their careers. The researchers noticed a common pattern in the stories shared by the next generation: Sons are often nurtured to become entrepreneurial, whether they are expected to take over the firm one day or to start a venture elsewhere. Daughters, however, receive little to no incentive to develop the leadership skills and entrepreneurial passion required to contribute to the family firm or start their own business.

In conversations with 26 children who were raised in 13 multi-generational family firms - some being centuries old - but not expected to work in the firm, the researchers found that:

Seven of the nine sons (78%), pursued entrepreneurial careers;

Only one among the 15 daughters (7%) gained an entrepreneurial education and engaged in entrepreneurship (7%);

Women were not encouraged to pursue entrepreneurship education, gain business experience, start a new venture;

Men rather than women received financial resources from the family to start their own business

"Even when these female non-successors have opportunities to acquire relevant knowledge and work to start a business, becoming entrepreneurial was still a challenging uphill battle," says Jaskiewicz, who believes the data reveals women do not pursue entrepreneurship outside of the family because they lacked sufficient emotional and financial support from the family.

It's hard to see more than a handful of stars from Princeton University, because the lights from New York City, Princeton and Philadelphia prevent our sky from ever getting pitch black, but stargazers who get into more rural areas can see hundreds of naked-eye stars -- and a few smudgy objects, too.

The biggest smudge is the Milky Way itself, the billions of stars that make up our spiral galaxy, which we see edge-on. The smaller smudges don't mean that you need glasses, but that you're seeing tightly packed groups of stars. One of the best-known of these "clouds" or "clusters" -- groups of stars that travel together -- is the Pleiades, also known as the Seven Sisters. Clusters are stellar nurseries where thousands of stars are born from clouds of gas and dust and then disperse across the Milky Way.

For centuries, scientists have speculated about whether these clusters always form tight clumps like the Pleiades, spread over only a few dozen lightyears.

"We call them 'open clusters' -- the 'open' part refers to the expectation that these things formed in a much denser group that then dispersed," said Luke Bouma, a graduate student in astrophysical sciences at Princeton and the lead author on an upcoming paper published by the American Astronomical Society. "But we never thought we'd be able to find the stars that were lost."

Then, two years ago, a machine-learning algorithm using data from the Gaia satellite identified that many far-flung stars are moving at the same speed and direction and could therefore be part of the same open cluster -- but as more of a stream or a string than a clump.

Now, a team of astrophysicists led by Bouma can confirm that one of these streams of stars, NGC 2516, also known as the Southern Beehive, extends at least 1,600 light-years -- 500 parsecs -- from tip to tip. To an Earth-based stargazer, that would look as big as 40 full moons, side by side, stretching across the sky.

"Gaia data let us trace the process of star cluster formation and dissolution in unprecedented detail -- but to complete the picture, we need independently estimated ages," said Lynne Hillenbrand, a 1989 Princeton alumna and a professor of astronomy at Caltech, who was not involved in this research. "Bouma's paper brings together several different methods to consistently age-date stars at both the core and the outer reaches of this cluster."

"In retrospect, the existence of this large stellar stream is not too surprising," said Bouma, who recently won the prestigious 51 Pegasus b Fellowship. One interpretation could be that a cluster starts as a tight clump that expands through time to form "tidal tails" stretching in front of it and behind it, as it moves through the Milky Way.

"The broader implication is that there are bound to be other enormous open clusters like this," he said. "The visible part of the cluster, where we can easily see the stars close together, may be only a small part of a much, much larger stream."

"I have seen the Southern Beehive many times through a pair of binoculars under the dark skies of Chile," said Gáspár Bakos, a professor of astrophysical sciences and the director of Princeton's program in planets and life, who was a co-author on the paper. "The cluster nicely fits the view of the binoculars, because its apparent size in the sky is something like the tip of my thumb at arm's length. It is curious to know, thanks to Luke's research, that the cluster actually spans an area as big as my entire palm held toward the sky."

Bouma and his colleagues used data from the Transiting Exoplanet Survey Satellite (TESS) to precisely measure the rotation rates of stars that the Gaia study had assigned to NGC 2516. The researchers demonstrated that many stars with similar masses are all spinning at (or very near) the same rate, confirming that they were born in the same stellar nursery.

Bouma has spent years developing the tools to measure a star's rotation so that he can calculate its age, a technique called gyrochronology (from the Greek words for "spin" and "time"). Our sun, which at the age of 4.6 billion years old is in its sedate middle age, rotates once every 27 days. The stars Bouma measured in NGC 2516 are rotating 10 times faster than our sun, because they are so much younger. Those stars are barely out of their infancy, only about 150 million years old.

"In addition to expanding our knowledge of this and other star clusters, Luke has given us an expanded list of young stars that we can search for planets," said Joshua Winn, Bouma's adviser and co-author and a professor of astrophysical sciences. "Finding planets around young stars will help us understand how planetary systems form and change with time."

"What's so surprising about this work -- what's so exciting -- is that we confirmed that Gaia, because it really precisely measures the positions and the motions of stars, can find these 'needles in the haystack' of the Milky Way," Bouma said. "Gaia can identify all the stars that are moving in the same direction, at the same rate. And we don't have to just trust the machine learning algorithm saying that they're related -- we can verify it with TESS data, using our gyrochronological technique."

This open cluster also has an intriguing connection with Greek mythology, Bouma said. "In the southern night sky, NGC 2516 is near a constellation called the Argo Navis, which was the boat sailed by Jason and the Argonauts to obtain the golden fleece." He added with a smile: "Jason and the Argonauts are sailing on a stream of stars made by the open cluster NGC 2516."

Carbon dioxide emissions in Los Angeles fell 33% in April of 2020 compared with previous years, as roads emptied and economic activity slowed due to the COVID-19 pandemic, according to a new study in Geophysical Research Letters. In the Washington, D.C./Baltimore region, emissions of carbon dioxide, or CO2, dropped by 34% during the same period.

The study was led by scientists at NASA's Jet Propulsion Laboratory (JPL), the National Institute of Standards and Technology (NIST) and the University of Notre Dame.

While the emissions reductions are significant, the method that scientists used to measure them may have the greater long-term impact.

In both locations, scientists had previously installed networks of sensors on rooftops and towers to monitor the concentration of CO2 in the air. They used the data from those sensor networks to estimate the drop in emissions.

This might seem an obvious way to estimate emissions, but this is not how it's usually done. Most cities estimate their emissions by tallying up the effects of activities that cause emissions, such as the number of vehicle miles traveled or the square footage of buildings heated and cooled. These are called "bottom up" methods because they are mostly based on activities on the ground.

This new study demonstrates that "top-down" methods, based on measuring the concentration of CO2 in the air, can produce reliable emissions estimates. Scientists were able to test those methods when emissions suddenly dropped due to COVID-19.

"This was a completely unanticipated experiment, and one we don't ever want to do again," said lead author and JPL data scientist Vineet Yadav. "But our results show that we were able to detect the onset of emissions reductions to within a few days."

Scientists have been developing top-down methods for measuring CO2 emissions for several years. "This study shows that the technology has matured enough to produce reliable results and can be put into operation," said NIST scientist and co-author Kimberly Mueller. That would give cities an important new tool in their efforts to reduce emissions.

Top-down estimates are difficult to achieve because most of the CO2 in the air above cities is not from local emissions. Most of it is there naturally, and some is emitted outside the city's borders and comes in on the wind. The trick is to figure out how much of the CO2 in the air above the city was generated locally.

"My Ph.D. adviser used to describe the atmosphere as a big cup of coffee," said Mueller. "You've added cream, and you're trying to unstir the coffee to see where and when you put the cream in."

To unstir the atmospheric coffee, scientists used data on wind speed, direction and other factors. This allowed them to estimate where within a city the emissions originated and how large they were.

Though difficult to achieve, top-down measurements have several advantages. First, they can provide relatively quick feedback on whether efforts to reduce emissions are working. If a city changes traffic patterns or increases public transit, for instance, top-down estimates can provide data on whether those efforts actually lead to reduced emissions.

In addition, a recent study, also co-authored by Mueller, indicated that U.S. cities often underestimate their emissions when using bottom-up methods alone. Another recent study showed that combining bottom-up with top-down methods increases accuracy. (Both studies were partly funded by NIST.)

"Accurate measurements are key to any strategy for managing greenhouse gas emissions," said James Whetstone, leader of NIST's greenhouse gas measurements group and a co-author of the study. "That's the only way to know if you are making progress toward your goals."

NIST, NASA and other research partners are using the sensor networks in Los Angeles and the Washington, D.C./Baltimore region to develop and test top-down methods as a way of achieving more accurate emissions estimates. This research project focuses on cities in part because cities account for a large and growing share of the world's CO2 emissions.

The 33% and 34% emissions drops in Los Angeles and the D.C./Baltimore region represent reductions relative to the average April emissions of the previous two years. The researchers used three different methods for detecting the change in emissions based on atmospheric measurements, all of which detected the drop occurring at the same time.

"These independent statistical tests on different pieces of the puzzle gave consistent results," said Notre Dame computational scientist and coauthor Subhomoy Ghosh. "This gives us confidence in the findings."

In addition, the methods appeared to work well in both locations, despite very different environmental conditions. In Los Angeles, relatively clean air comes in off the Pacific. D.C. and Baltimore, on the other hand, regularly receive emissions from cities and power plants to the west. Also in D.C. and Baltimore, emissions models have to account for the effects of spring, when plants turn green again and start pulling CO2 from the air. Los Angeles experiences less seasonal variation in uptake by plants.

"These methods were robust enough to work in very different settings," Mueller said. "The fact that these methods worked in both locations mean the results were not a fluke."

A new study at the University of Chicago has determined that restoring a single microbial species -- Bacteroides sp. CL1-UC (Bc) -- to the gut microbiome at a key developmental timepoint can prevent antibiotic-induced colitis in a mouse model of the condition. The results, published on June 7 in Gastroenterology, have major implications for humans dealing with inflammatory bowel disease (IBD), and underscore the impact of early childhood exposures on health throughout the lifetime.

Prior studies in human patients have found that early life exposure to antibiotics can skew the gut microbiome, causing dysbiosis, or an imbalance of the microbial populations in the gut, which is correlated with increase risk for developing pediatric IBD.

"We know that the kinds of microbes that you're exposed to early in life actually determine how your immune system develops," said senior author Eugene Chang, MD, Martin Boyer Professor of Medicine at UChicago. "Our immune system learns to recognize our own selves, and the trillions of microbes in our gut -- they're 'us' as well, so our immune system has to learn to tolerate these organisms, just as it tolerates our own cells. Early exposure to antibiotics can eradicate some of the organisms that are essential for educating the immune system to develop immune tolerance."

Due to the challenges of conducting such studies in human patients, the researchers opted to use a common model for studying colitis: mice that lack a gene known as IL-10 (IL-10-/-). "This mouse model has been established as being genetically susceptible to IBD, and we know that the gut microbiome plays a crucial role in the development of colitis in this model," said first author Jun Miyoshi, MD, PhD, a Senior Assistant Professor in the Department of Gastroenterology and Hepatology at Kyorin University School of Medicine, and a former postdoctoral scholar at UChicago.

While only very rarely do these mice develop spontaneous colitis without any intervention in a clean environment, if their mothers are exposed to antibiotics during pregnancy and nursing, the disrupted microbiome can be transmitted to the pups at an early age. Around 30% of pups with this vertically transmitted disrupted microbiome go on to develop colitis.

The investigators used a technique known as shotgun metagenomic sequencing to screen the fecal microbiomes of IL-10-/- mice that had antibiotic-induced dysbiosis, alongside an untreated control group, and identify specific microbial species that might distinguish the two groups. This led them to members of the bacterial phylum Bacteroides.

One clue of the phylum's importance was that Bacteroides was very abundant in the microbiomes of untreated mice, but completely lacking in the mice that had been exposed to antibiotics. What's more, the researchers never saw Bacteroides in the treated mice that did not go on to develop colitis -- but they often found Bacteroides in the guts of mice that did end up with the condition.

"These bacteria were eradicated by early exposure to antibiotics and were essential for educating the immune system in developing immune tolerance," said Chang. "When those mice later acquired the bacteria, their immune system had never seen it. It was viewed as foreign, not as self, and their immune systems reacted to it."

In an effort to determine whether restoring important Bacteroides back to the microbiome could correct the dysbiosis, the researchers honed in on a particularly abundant species known as Bacteroides sp. CL1-UC (Bc). They tried adding Bc back to the microbiomes of the mice with dysbiosis at two timepoints: around infancy (three weeks of age) and adulthood (11 weeks of age).

Engrafting Bc into the younger mice, during the critical immune system developmental window, corrected their dysbiosis and prevented colitis, but adding Bc back to adult mice could not correct the dysbiosis, and even worsened their colitis.

"This shows that you can't just restore the missing bacteria at any time point, it has to be at a specific time early in life to have a beneficial effect," said Chang. "In young animals, we know that the immune system is developing, it's naive, it has to be taught, and it's taught by being exposed to certain kinds of microbes. In some ways, it's similar to a peanut allergy -- early exposure to the antigen can tolerize the immune system to help avoid a peanut allergy, but it has to happen within a very finite window."

The researchers were surprised to learn that restoring a single microbe was enough to correct lifelong dysbiosis, and said it highlighted how relatively small changes can have a dramatic impact on a system. "It's like the tall trees of the Amazon rainforest," said Chang. "You need the tall trees, because if you don't have them, the ecosystem below cannot develop properly. But if you have those trees in place, the rest of the ecosystem will flourish."

The results also go against popular theories on the origin of IBD. "There's a misconception that colitis is caused by a classical pathogen, like salmonella, and scientists have spent years looking for a culprit," said Chang. "But what our data are pointing to is that these diseases are caused by our own commensal microbes. They are present in the normal, healthy microbiome, but given the right circumstance and opportunity, they can transform into disease-promoting microbes."

While this early study was proof-of-concept, if the results translate to humans, the ripple effects are likely to be far-reaching. "This shows that we probably have to rethink our approach to these kinds of complex immune disorders," said Chang. "We can see that risk is developing early in life -- even in utero -- and so this has implications for practices such as C-sections and formula feeding, which can impact the microbes an infant is exposed to. What this says to me is that, as physicians, we need to shift our thinking to not what immediately preceeds these diseases but what happens early in life. That's where we need to intervene for these patients."

TROY, N.Y. -- More strategic and coordinated travel restrictions likely could have reduced the spread of COVID-19 in the early stages of the pandemic. That's according to new research published in Communications Physics. This finding stems from new modeling conducted by a multidisciplinary team of scientists and engineers at Rensselaer Polytechnic Institute.

The researchers evaluated the distance between countries in terms of air travel, a more complex measurement than simply mapping physical distance. For instance, while China and Thailand may be geographically more proximate to one another, if there are significantly more flights between China and the United States, the chance of disease spread may be higher.

"This is considered a global problem," said Mamadou Diagne, an assistant professor of mechanical, aerospace, and nuclear engineering at Rensselaer, "so we wanted to know if coordinated action could be taken to mitigate contamination rates all across the world."

By mapping and analyzing the global mobility network through air traffic patterns, the researchers were able to determine the level of connection between various nations and develop a model that can predict which countries are closer to one another in terms of disease spread. The model was able to successfully predict when the virus arrived in the United States.

Using this approach, the team examined the effectiveness of various travel restrictions countries implemented in an effort to slow the transmission of the virus that causes COVID-19.

"For example, we found that the Chinese lockdown reduced the arrival time of the virus in uninfected countries by about 10 days," said Jianxi Gao, an assistant professor of computer science at Rensselaer. "And, it reduced the number of infections by 6 million globally."

Travel restrictions enacted by other nations, including entry bans, global travel bans, and lockdowns, also helped to reduce the global spread. However, the Rensselaer team found that these actions could have been significantly more effective had countries worked in concert with one another.

"According to the data we collected, about 63.2% percent of travel restrictions were ineffective," said Lu Zhong, a postdoctoral researcher in mechanical, aerospace, and nuclear engineering. "Because the travel restrictions were done in an uncoordinated way, they failed to contribute to the global good."

Diagne, Gao, and Zhong found that redundant or unnecessary travel restrictions also affected the global economy. A more efficient approach, they said, could mitigate economic harm.

BOSTON - Current guidelines recommend stopping cervical cancer screening at age 65, but women over age 65 make up over one in five new cervical cancer diagnoses, and are twice as likely to die after a cervical cancer diagnosis compared to younger women. New research from Boston Medical Center found that fewer than one in three women aged 64 to 66 met the criteria to discontinue cervical cancer screening while looking at patients with both private insurance and from a safety-net hospital setting. Published in Gynecologic Oncology, researchers found that even among women with 10 years of continuous insurance coverage, 41.5 percent did not qualify to end screening and most women did not receive adequate screening in the ten years leading up to this important screening decision.

The majority of women aged 65 and older may be at risk for cervical cancer due to inadequate screening or preexisting high-risk conditions. Study findings show that up to 20 percent of women reported a medical condition or a history of screening abnormalities that make this screening necessary beyond the age of 65. This highlights the need to educate patients and healthcare providers on the importance of ensuring adequate cervical cancer screening at ages 55 to 65, and also on high-risk conditions that necessitate screening beyond age 65. When data are adjusted for patient hysterectomies, the incidence of cervical cancer is highest among women ages 65 to 69 and remains elevated through age 85.

"Providers need to be aware that cervical cancer is a growing problem among women aged 65 and older, and that it is preventable," says Rebecca Perkins, MD, MPH, obstetrics & gynecology physician at BMC. "It's imperative for providers to proactively ensure that their patients receive adequate screening between the ages of 55 and 65 to decrease preventable cancers in women over the age of 65, and to make sure that their patients are adequately screened to be able to safely exit screening, if their health history qualifies."

The study data included 590,901 women aged 64 with employer-sponsored insurance enrolled in the national Truven MarketScan database between 2016 and 2018, and 1544 women aged 64 to 66 receiving primary care at a safety net health center in 2019, identified through an electronic health record query. Screening exit eligibility was determined using the current guidelines that include: no evidence of cervical cancer or HIV-positive status, no evidence of cervical pre-cancer in the past 25 years, and evidence of either a hysterectomy with removal of the cervix or evidence of fulfilling the screening exit criteria. The exit criteria are defined as two human papillomavirus (HPV) screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result (screening with HPV testing or HPV/Pap co-testing provides more long term reassurance against cancer development than Pap testing alone).

Data from both the safety net hospital and national claims database indicated that fewer than half of women aged 64 to 66 had documentation of sufficient screening to fulfill the exit criteria. Guidelines specify that patients with immunosuppression, histories of abnormal results or cervical precancer, or cancer should continue screening. Current screening exit criteria are complex and require a detailed review of at least ten years of medical record documentation, which can create barriers to applying the guidelines to clinical practice.

"No patient should ever discontinue screening based on age alone without their healthcare provider completing a thorough review of their medical record," says Perkins, also an associate professor of obstetrics and gynecology at Boston University School of Medicine. "Improved cervical cancer screening in women 55 years and older may reduce cancer rates and mortality in women aged 65 and over."

Possible solutions to improve these rates include a Medicare-funded cancer prevention visit where the need for a cervical cancer screening is reviewed, and the optimization of electronic medical records to prompt a review of the cervical cancer exit screening criteria prior to a patient's screening discontinuation.

GAINESVILLE, Fla. --- A more reliable way of estimating the size of megalodon shows the extinct shark may have been bigger than previously thought, measuring up to 65 feet, nearly the length of two school buses. Earlier studies had ball-parked the massive predator at about 50 to 60 feet long.

The revised estimate is the result of new equations based on the width of megalodon's teeth - and began with a high school lesson that went awry.

Victor Perez, then a doctoral student at the Florida Museum of Natural History, was guiding students through a math exercise that used 3D-printed replicas of fossil teeth from a real megalodon and a set of commonly used equations based on tooth height to estimate the shark's size. But something was off: Students' calculations ranged from about 40 to 148 feet for the same shark. Perez snapped into trouble-shooting mode.

"I was going around, checking, like, did you use the wrong equation? Did you forget to convert your units?" said Perez, the study's lead author and now the assistant curator of paleontology at the Calvert Marine Museum in Maryland. "But it very quickly became clear that it was not the students that had made the error. It was simply that the equations were not as accurate as we had predicted."

Although the equations have been widely used by scientists since their publication in 2002, the classroom exercise revealed they generate varying size estimates for a single shark, depending on which tooth is measured.

"I was really surprised," Perez said. "I think a lot of people had seen that study and blindly accepted the equations."

For more than a century, scientists have attempted to calculate the size of megalodon, whose name means "big tooth." But the only known remains of the fearsome shark that dominated oceans from about 23 to 3.6 million years ago are fossilized teeth and a few, rare vertebrae. Like other sharks, the rest of megalodon's skeleton, including its jaw, was composed of lightweight cartilage that decomposed quickly after death. Tooth enamel, however, "preserves really well," Perez said. "It's probably the most structurally stable thing in living organisms." Megalodon sharks shed thousands of teeth over a lifetime, leaving abundant traces of the species in the fossil record.

The most accepted methods for estimating the length of megalodon have used great white sharks as a modern proxy, relying on the relationship between tooth size to total body length. While great white sharks and megalodon belong to different families, they share similar predatory lifestyles and broad, triangular teeth serrated like steak knives - ideal adaptations for hunting large, fleshy marine mammals such as whales and dolphins, Perez said.

But these methods also present a challenge: To generate body length estimates, they require the researcher to correctly identify a fossil tooth's former position in a megalodon jaw. As in humans, the size and shape of shark teeth vary depending on where they're located in the mouth, and megalodon teeth are most often found as standalone fossils.

So, Perez was ecstatic when fossil collector Gordon Hubbell donated a nearly complete set of teeth from the same megalodon shark to the Florida Museum in 2015, reducing the guesswork. After museum researchers CT scanned the teeth and made them available online, Perez collaborated with teacher Megan Higbee Hendrickson on a plan to incorporate them into her middle school curriculum at the Academy of the Holy Names school in Tampa.

"We decided to have the kids 3D-print the teeth, determine the size of the shark and build a replica of its jaw for our art show," Hendrickson said.

Perez and Hendrickson co-designed a lesson for students based on the then-most popular method for estimating shark size: Match the tooth to its position in the shark jaw, look up the corresponding equation, measure the tooth from the tip of the crown to the line where root and crown meet and plug the number into the equation.

After a successful pilot test of a few teeth with Hendrickson's students, he expanded the lesson plan to include the whole set of megalodon teeth for high school students at Delta Charter High School in Aptos, California. Perez expected a slight variability of a couple millimeters in their results, but this time, variations in students' estimates shot to more than 100 feet. The farther a tooth position was from the front of the jaw, the larger the size estimate.

After Perez detailed the lesson's results in a fossil community newsletter, he received an email from Teddy Badaut, an avocational paleontologist in France. Badaut suggested a different approach. Why not measure tooth width instead of height? Previous research had suggested tooth width was limited by the size of a shark's jaw, which would be proportional to its body length.

Ronny Maik Leder, then a postdoctoral researcher at the Florida Museum, worked with Perez to develop a new set of equations based on tooth width.

By measuring the set of teeth from Hubbell, "we could actually sum up the width of the teeth and get an even better approximation of the jaw width," Perez said.

The researchers analyzed sets of fossil teeth from 11 individual sharks, representing five species, including megalodon, its close relatives and modern great white sharks.

By measuring the combined width of each tooth in a row, they developed a model for how wide an individual tooth was in relation to the jaw for a given species. Now when a paleontologist unearths a lone megalodon tooth the size of their hand, they can compare its width to the average obtained in the study and get an accurate estimate of how big the shark was.

"I was quite surprised that indeed no one had thought of this before," said Leder, now director of the Natural History Museum in Leipzig, Germany. "The simple beauty of this method must have been too obvious to be seen. Our model was much more stable than previous approaches. This collaboration was a wonderful example of why working with amateur and hobby paleontologists is so important."

Perez cautioned that because individual sharks vary in size, the team's methods still have a range of error of about 10 feet when applied to the largest individuals. It's also unclear exactly how wide megalodon's jaw was and difficult to guess based on teeth alone - some shark species have gaps between each tooth while the teeth in other species overlap.

"Even though this potentially advances our understanding, we haven't really settled the question of how big megalodon was. There's still more that could be done, but that would probably require finding a complete skeleton at this point," he said.

Perez continues to teach the megalodon tooth lesson, but its focus has changed.

"Since then, we've used the lesson to talk about the nature of science - the fact that we don't know everything. There are still unanswered questions," he said.

For Hendrickson, the lesson sparked her students' enthusiasm for science in ways that textbooks could not.

"Victor was an amazing role model for the kids. He is the personification of a young scientist that followed his childhood interest and made a career out of it. So many of these kids had never worked with or spoken to a scientist who respected their point of view and was willing to answer their questions."

Leder and Badaut co-authored the study.

In the quest for healthy aging and longer lifespan, Danish researchers at the University of Southern Denmark have collaborated with Swedish researchers at Karolinska Institutet to explore the anti-aging effects of football and team handball training in women.

In a current study published in Scientific Reports, the researchers investigated the effects of lifelong regular exercise on two of the central hallmarks of aging combined and showed that football and team handball have a positive effect on telomere length and mitochondrial function in women.

"Our legacy consists of DNA that is packed in chromosomes. When cells divide, the inheritance is copied, but with each cell division the ends of the DNA threads get shorter. The so-called telomeres are shortened, which causes us to age. It is remarkable that engaging in team sports such as football and handball helps women to maintain longer telomeres and healthy mitochondria. It may potentially increase their health span and, ultimately, lifespan, as shorter telomeres and mitochondrial dysfunction are both associated with a number of age-related diseases and mortality," says senior researcher Muhammad Asghar, the study's shared senior author, of the Department of Medicine, Solna at Karolinska Institutet.

Younger biological age in the cells as evaluated by telomere length

"We've recently shown that 65-80-year-old male football players are in excellent physical shape in comparison to untrained age-matched individuals, evidenced by markedly higher aerobic fitness, muscle mass and bone strength as well as a younger biological age in the cells as evaluated by telomere length," says Professor Peter Krustrup, the study's shared senior author, of the Department of Sports Science and Clinical Biomechanics at the University of Southern Denmark, and adds:

"Interestingly, the present study shows the same pattern, including a positive effect on mitochondrial health, in 60-80-year-old female team handball players, thereby supporting the evidence for an anti-aging potential of team sports."

"In addition to the positive findings in elderly team handball players, we observed that young female elite football players have ~23% longer telomeres in specific blood cells compared to untrained age-matched women," says PhD Marie Hagman, the study's first author, of the Department of Sports Science and Clinical Biomechanics at the University of Southern Denmark.

"These results are striking because differences in telomere length of that magnitude are not normally found in young participants. It should be noted, however, that this is a cross-sectional study and that our findings need to be confirmed by future randomised controlled trials," Hagman explains.

The study involved 129 healthy, non-smoking women, including young elite football players (YF, n=29, 18-30 yrs), young untrained controls (YC, n=30, 18-30 yrs), elderly team handball players (EH, n=35, 60-80 yrs) and elderly untrained controls (EC, n=35, 60-80 yrs). The study was the first to investigate the effects of lifelong regular exercise in humans on two of the central aging hallmarks combined.

Elite football and lifelong team handball training are associated with beneficial anti-aging cellular effects

The results of the study showed that elite football and lifelong team handball training are associated with beneficial anti-aging cellular effects in women. Specifically, young elite football players demonstrated higher telomere length and higher mtDNA copy number compared to young untrained controls, while elderly team handball players showed healthy mitochondria compared to elderly untrained controls. These cellular adaptations were also positively correlated with VO2max and the amount of weekly exercise, emphasizing the importance for these women, irrespective of age, to maintain a reasonable fitness and activity level.

Climate change and social inequality are two pressing issues that often overlap. A new study led by Princeton researchers offers a roadmap for cities to address inequalities in energy use by providing fine-grained methods for measuring both income and racial disparities in energy use intensity. Energy use intensity, the amount of energy used per unit floor area, is often used as a proxy for assessing the efficiency of buildings and the upgrades they receive over time. The work could guide the equitable distribution of rebates and other measures that decrease energy costs and increase efficiency.

Examining inequality in cities has been hampered by a lack of energy use data at fine spatial scales within cities. Until now, only Los Angeles has been able to use a data-driven approach to shine a light on where energy use inequalities exist, focusing specifically on the effect of income disparities. But according to new results reported in Proceedings of the National Academy of Sciences, to truly understand and fully address energy use inequality, cities must take an even more nuanced approach--one that unpacks race-related disparities from income. As the authors report, examining the issue solely through the lens of income risks missing significant race-related inequalities that exist beyond income effects.

"Often, in discussions about social justice, people sometimes ask, 'Oh, how do you know it's a race effect and not 'just' an income effect?'" said co-author Anu Ramaswami, a professor of civil and environmental engineering and the High Meadows Environmental Institute at Princeton University. "This paper actually shows you the data, that there's a structurally linked income-race effect, and an additional race effect even within the same income group."

Ramaswami and her colleagues arrived at their findings by studying two cities, Tallahassee, Florida, and St. Paul, Minnesota. The findings showed that when evaluating annual energy use, homes in the lowest income neighborhoods on average used 25-60% higher energy use per square foot compared to the highest income neighborhoods. What was more surprising was that within the income groups, predominantly non-white neighborhoods had higher energy use intensity compared to predominantly white neighborhoods.

"We were struck when we first saw these patterns," said Ramaswami, who also is Princeton's Sanjay Swani '87 Professor of India Studies and director of the Chadha Center for Global India.

The results were even starker considering seasonal energy use in summer and winter. Focusing on seasonal energy use intensity, the study uncovered disparities by income, and disparities by race within the lowest-income group, that can be greater than 150%, which are five times larger than the 25% disparity previously known in U.S. cities, based on the limited data availability in prior studies. The study found that households in low-income non-white neighborhoods report higher energy use intensity, reflective of lower energy efficiency of the buildings, as well as lower participation in rebate programs.

The method she and her colleagues developed can be applied in other cities and utility sectors (mobility, water, etc.) and is available now for adoption by cities interested in addressing racial inequalities. "We don't think it's only these two cities," Ramaswami said. "These effects are probably happening everywhere."

Inequalities surrounding income and race in the U.S. tend to be conflated because lower income communities often have higher non-white populations, while higher income areas tend to be predominantly white. To untangle these variables, Ramaswami and her co-authors worked with city officials and utility companies to obtain detailed energy use data.

"Part of the problem is that race and income are so intertwined, you need fine-scale data to actually unpack inequality," Ramaswami said. "Typically, cities get energy use data at the zip code level, which is very coarse, but we got data at the level of census blocks through a unique collaboration with our partner cities and utilities, who are committed to understanding baseline inequalities in their neighborhoods."

In total, the researchers obtained anonymized and aggregated data from utilities covering all 90,000 households in Tallahassee, and all 110,000 in St. Paul. They divided total household energy use in a neighborhood by the total square footage of the dwellings to compute the average energy use intensity for that neighborhood. They then compared energy use intensity across different neighborhood groups partitioned into five income brackets, and further by the racial composition of the neighborhoods within each income bracket.

The results revealed a number of surprises. In St. Paul, for example, the lowest income group had a 27% higher annual energy use intensity (use per square foot) compared to the highest income group. St Paul's result is comparable to the 25% disparity by income seen in Los Angeles. However, Tallahassee's disparity in annual electricity use intensity by income was found to be more than double at 66%. Furthermore, when the researchers further partitioned the income groups by racial composition of the census block groups, they found substantial additional disparities by race even within the same income groups. For example, in St. Paul, the poorest predominantly non-white neighborhoods had a 40% higher energy use intensity compared to poorest predominantly white neighborhoods. Such racial disparity was seen within all income brackets except for the very wealthiest block groups, which were majority white to begin with.

When the team took a closer look at seasonal energy use, -- i.e. energy used for heating and cooling in winter and summer--they found an up to 167% disparity in electricity use intensity between the lowest and highest -earning households in St. Paul, with the lowest-earning households footing that outsized energy burden. In Tallahassee, seasonal energy use showed large racial disparities within the lowest income group of the order of 156%.

"To my knowledge, this is the first study to show inequalities in urban energy use by race, and to show that it's different from energy use inequality by income," says Karen Seto, the Frederick C. Hixon Professor of Geography and Urbanization Science at Yale University, who was not involved in the research. "The study corroborates other studies that show significant within-city inequalities" by both race and income, she said, "whether it's exposure to heat or green space."

The researchers also examined household participation in several types of rebate programs designed to increase energy use efficiency and decrease costs. They found that homes in wealthier predominantly white neighborhoods were more likely to participate in rebate programs, while poorer predominantly non-white ones tended to slip through the cracks.

"Making this type of data visible is helpful for making people understand that infrastructure-related racial disparities are not just some abstract thing--it's real and you can see it in the data," Ramaswami said. "We all say we want social justice, but to get to that, it helps to be quantitative."

Ramaswami and her colleagues hope that cities across the country adopt their method to better understand their own energy equity dynamic. They are already working with officials in Austin, Texas, to apply this new approach.

Ultimately, they also hope to follow up on their findings to determine what is actually driving disparities in energy use intensity and rebate participation, so cities can use that information to further close the gap on inequalities.

"The new understanding gained from this study is already quite a lot," said Kangkang Tong, first author of the study and a postdoctoral researcher in civil and environmental engineering at Princeton University. "But it will take another several studies to really understand the reasons behind our findings, to help communities improve their energy use efficiency."

The study also addresses fundamental questions about the geographical scale researchers can use to measure social inequality in urban areas. The researchers found that choosing to study social inequality across city blocks as the unit of analysis provides different results than studying inequality across larger block groups or even larger census tracts. This is part of a fundamental question that scholars from many disciplines -- including geography, public health, computer science, mathematics, and political science -- are grappling with, called the modifiable areal unit problem. The problem is that measures of dispersion and inequality change as the spatial unit area of observation is modified - whether it is a city block, block group, census tract, or zip code. Ramaswami said the PNAS paper is the first to characterize the modifiable areal unit problem for the issue of energy use inequality in cities by exploring multiple metrics for energy use inequality across a range of scales. These findings are highly policy relevant because it means measuring disparity ratios from data aggregated at the block-level could give very different results from computing them from block-group or census tract-level data.

"This is also another area for further research, wherein policy-relevant questions can trigger fundamental scientific discoveries." Tong said.

High blood pressure, or hypertension, is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. And key to treating patients with conditions ranging from chest pain to stroke is understanding the intricacies of how the cells around arteries and other blood vessels work to control blood pressure. While the importance of metals like potassium and calcium in this process are known, a new discovery about a critical and underappreciated role of another metal - zinc - offers a potential new pathway for therapies to treat hypertension.

The study results were published recently in Nature Communications.

All the body's functions depend on arteries channeling oxygen-rich blood - energy - to where it's needed, and smooth muscle cells within these vessels direct how fast or slow the blood gets to each destination. As smooth muscles contract, they narrow the artery and increase the blood pressure, and as the muscle relaxes, the artery expands and blood pressure falls. If the blood pressure is too low the blood flow will not be enough to sustain a person's body with oxygen and nutrients. If the blood pressure is too high, the blood vessels risk being damaged or even ruptured.

"Fundamental discoveries going back more than 60 years have established that the levels of the calcium and potassium in the muscle surrounding blood vessels control how they expand and contract," say lead author Ashenafi Betrie, Ph.D., and senior authors Scott Ayton, Ph.D., and Christine Wright, Ph.D., of the Florey Institute of Neuroscience and Mental Health and The University of Melbourne in Australia.

Specifically, the researchers explain, potassium regulates calcium in the muscle, and calcium is known to be responsible for causing the narrowing of the arteries and veins that elevate blood pressure and restrict blood flow. Other cells that surround the blood vessel, including endothelial cells and sensory nerves, also regulate the calcium and potassium within the muscle of the artery, and are themselves regulated by the levels of these metals contained within them.

"Our discovery that zinc is also important was serendipitous because we'd been researching the brain, not blood pressure," says Betrie. "We were investigating the impact of zinc-based drugs on brain function in Alzheimer's disease when we noticed a pronounced and unexpected decrease in blood pressure in mouse models treated with the drugs."

In collaboration with researchers at the University of Vermont's Larner College of Medicine in the United States and TEDA International Cardiovascular Hospital in China, the investigators learned that coordinated action by zinc within sensory nerves, endothelial cells and the muscle of arteries triggers lower calcium levels in the muscle of the blood vessel. This makes the vessel relax, decreasing blood pressure and increasing blood flow. The scientists found that blood vessels in the brain and the heart were more sensitive to zinc than blood vessels in other areas of the body - an observation that warrants further research.

"Essentially, zinc has the opposite effect to calcium on blood flow and pressure," says Ayton. "Zinc is an important metal ion in biology and, given that calcium and potassium are famous for controlling blood flow and pressure, it's surprising that the role of zinc hasn't previously been appreciated."

Another surprising fact is that genes that control zinc levels within cells are known to be associated with cardiovascular diseases including hypertension, and hypertension is also a known side effect of zinc deficiency. This new research provides explanations for these previously known associations.

"While there are a range of existing drugs that are available to lower blood pressure, many people develop resistance to them," says Wright, who added that a number of cardiovascular diseases, including pulmonary hypertension, are poorly treated by currently available therapies. "New zinc-based blood pressure drugs would be a huge outcome for an accidental discovery, reminding us that in research, it isn't just about looking for something specific, but also about just looking."

A study conducted by a group of Brazilian researchers contributes to a deeper understanding of the molecular basis for schizophrenia, and potentially to the development of more specific and effective treatments for the disease. The medications currently available on the market act generically on the brain and can have severe adverse side effects.

Treatment of post-mortem samples from the hippocampus of schizophrenic patients with an NMDA receptor antagonist pointed to biological processes associated with the disease that are specific to neurons and oligodendrocytes. NMDA receptors are neurotransmitter receptors located in the postsynaptic membrane of neurons, and receive signals across the synapse from previous nerve cells.

The antagonist in question was MK-801, a drug that alters the neurotransmitter function of glutamate, mimicking in vitro what happens in schizophrenia (glutamate is the brain's primary excitatory neurotransmitter). Neurons treated with the substance displayed oxidative stress, one of the factors that can lead to brain degeneration, and apoptosis (programmed cell death). Oligodendrocytes, which synthesize the myelin sheath that insulates axons, were not altered in the same way. On the other hand, oligodendrocytes displayed differences associated with protein synthesis and myelin membrane organization.

The Laboratory of Neuroproteomics at the Institute of Biology of the University of Campinas (UNICAMP) used post-mortem brain tissue samples from patients with schizophrenia. The results, obtained in collaboration with the group led by Helder Nakaya, a professor at the University of São Paulo's School of Pharmaceutical Sciences (FCF-USP), are reported in an article published in European Archives of Psychiatry and Clinical Neuroscience.

"After culturing neurons and oligodendrocytes in the lab and treating them with MK-801, we analyzed the proteins in the brain and each cell type, cross-referencing the data. This enabled us to identify differences specific to neurons or oligodendrocytes, or common to both," said Daniel Martins-de-Souza, principal investigator for the study and head of the laboratory, which is supported by São Paulo Research Foundation - FAPESP.

Previous research found abnormal levels of glutamate in the brains of schizophrenic patients and linked glutamatergic neurotransmission dysfunction to NMDA receptor hypofunction. Glutamatergic neurotransmission is essential for cognition, learning and memory in humans.

"The treatment of neural cells with MK-801 revealed that neurons, oligodendrocytes and astrocytes are affected but present different responses to NMDA receptor hypofunction. NMDA receptor activation in oligodendrocytes is involved with their maturation, metabolic modulation and myelination around axons," the researchers write in the article.

An axon is part of a neuron that carries nerve impulses away from the cell body. Each neuron typically has one axon that connects it with other neurons via their synapses. Its filaments are insulated by a sheath made of myelin, a lipid-rich substance that prevents loss of energy during the transmission of electrical impulses between neurons.

"Thus, understanding the effects of glutamatergic dysregulation in both neurons and oligodendrocytes is crucial to a grasp of the role of these cellular counterparts in schizophrenia, especially in the hippocampal context," the article continues, adding that "we were able to find proteomic signatures in common between the hippocampus and MK-801-treated neurons, and between the hippocampus and the MK-801-treated oligodendrocytes". These findings will contribute to the development of treatments better targeted to the different dysfunctional biological processes in the various brain cell types.

According to PhD candidate Giuliana da Silva Zuccoli, first author of the article, lack of myelin or improper sheath formation may be part of the reason for cognitive and memory problems in schizophrenia.

Last year a study conducted at UNICAMP's Laboratory of Neuroproteomics with FAPESP's support had associated schizophrenia with dysfunctional oligodendrocytes that produce defective myelin.

FAPESP also supported the research that resulted in the article through funding for six other projects: 2018/14666-4, 2017/25588-1, 2019/00098-7, 2017/50137-3, 2012/19278-6 and 2013/08216-2.

23 million cases worldwide

Considered a severe debilitating mental disorder, schizophrenia affects some 23 million people worldwide, including 1.5 million Brazilians, according to the Pan American Health Organization (PAHO). It is characterized by thoughts or experiences that seem out of touch with reality, disorganized speech or behavior, and reduced participation in daily activities. Treatment involves a combination of medications, psychotherapy and specialized care. A clinical assessment is required to diagnose schizophrenia.

A promising methodology was developed last year to create a blood test that can diagnose schizophrenia by Brazilian researchers affiliated with the Federal University of São Paulo (UNIFESP) and UNICAMP. The test is the first to detect the disorder by analyzing biochemical and molecular alterations (more at: agencia.fapesp.br/34356).