The intestinal epithelium, made up of a layer of cells that lines the intestine, plays an important role in IBD because it can be easily disrupted during gut inflammation. A specialized type of epithelial cells are Paneth cells. The antimicrobial peptides these cells produce help regulate the gut microbiota, or the community of microorganisms that exist in the gut.

A research team led by Declan F. McCole, a biomedical scientist and IBD expert at the University of California, Riverside, reports in their mouse study that reduced activity of the IBD risk gene PTPN2 in intestinal epithelial cells can lead to a decrease in the production of Paneth cell antimicrobial peptides.

The study, published in the journal Cellular and Molecular Gastroenterology and Hepatology, establishes a critical link between PTPN2 and Paneth cells that plays a major role in maintaining normal gut microbe properties.

“This study develops our focus on improving personalized medicine approaches in IBD by understanding how patients with variants in the PTPN2 gene develop IBD,” said McCole, a professor of biomedical sciences in the School of Medicine. “Loss of PTPN2 can lead also to selective loss of Paneth cells in the intestinal epithelium. This loss of PTPN2 causes significant changes in the gut microbiota and increases a particular E. coli.”

Escherichia coli, or E. coli, are bacteria found in the environment, foods, and intestines of people and animals. McCole explained that the E. coli in question, the adherent-invasive E. coli, or AIEC, is increased in IBD and worsens inflammation. First identified in Crohn’s disease patients, AIEC can adhere to and invade epithelial cells as well as immune cells called macrophages.

“AIEC are the strongest candidate for a causal role for bacteria in IBD,” he said.

According to McCole, Paneth cells do not function properly in many patients living with IBD, and this can serve as a marker of disease. The antimicrobial peptides these cells produce are crucially relevant to the intestine’s protective barrier for regulating the relative proportions of bacteria and their interactions with each other. They also help neighboring intestinal stem cells function better.

“We know that in IBD, Paneth cells are often unable to produce sufficient antimicrobial peptides or respond appropriately to gut bacteria,” McCole said. “These functional defects can also be associated with changes in the structure of Paneth cells that reduce their ability to secrete the protective antimicrobial peptides, leading to increases in the populations of bacteria associated with IBD, such as AIEC. These structural changes in the appearance of Paneth cells can also serve as a marker of disease in IBD, especially Crohn’s disease.”

McCole was joined in the study by Vinicius Canale, Marianne R. Spalinger, Rocio Alvarez, Anica Sayoc-Becerra, Golshid Sanati, Salomon Manz, Pritha Chatterjee, Alina N. Santos, Hillmin Lei, Sharon Jahng, Timothy Chu, and Ali Shawki of UCR; Elaine Hanson and Lars Eckmann of UC San Diego; and André J. Ouellette of the University of Southern California.

The study was supported by the Crohn’s and Colitis Foundation; Swiss National Science Foundation; American Gastroenterological Association; Science Without Borders Program; and California Institute of Regenerative Medicine.

“This work sets the foundation for our new research project that will identify pharmacologic agents capable of rescuing Paneth cell function and reducing the contributions of microbes to intestinal inflammation,” McCole said.

How OH itself forms in the atmosphere was viewed as a complete story, but in new research published in Proceedings of the National Academy of Sciences, a research team that includes Sergey Nizkorodov, a University of California, Irvine professor of chemistry, report that a strong electric field that exists at the surface between airborne water droplets and the surrounding air can create OH by a previously unknown mechanism.

It’s a finding that stands to reshape how scientists understand how the air clears itself of things like human-emitted pollutants and greenhouse gases, which OH can react with and eliminate. “You need OH to oxidize hydrocarbons, otherwise they would build up in the atmosphere indefinitely,” said Nizkorodov.

“OH is a key player in the story of atmospheric chemistry. It initiates the reactions that break down airborne pollutants and helps to remove noxious chemicals such as sulfur dioxide and nitric oxide, which are poisonous gases, from the atmosphere,” said Christian George, an atmospheric chemist at the University of Lyon in France and lead author of the new study. “Thus, having a full understanding of its sources and sinks is key to understanding and mitigating air pollution.”

Before, researchers assumed that sunlight was the chief driver of OH formation.

“The conventional wisdom is that you have to make OH by photochemistry or redox chemistry. You have to have sunlight or metals acting as catalysts,” Nizkorodov said. “What this paper says in essence is you don’t need any of this. In the pure water itself, OH can be created spontaneously by the special conditions on the surface of the droplets.”

The team built on research from Stanford University scientists led by Richard Zare that reported spontaneous formation of hydrogen peroxide on the surfaces of water droplets. The new findings help interpret the unexpected results from the Zare group.

The team measured OH concentrations in different vials — some containing an air-water surface and others containing only water without any air — and tracked OH production in darkness by including a “probe” molecule in the vials that fluoresces when it reacts with OH.

What they saw is that OH production rates in darkness mirror those and even exceed rates from drivers like sunlight exposure. “Enough of OH will be created to compete with other known OH sources,” said Nizkorodov. “At night, when there is no photochemistry, OH is still produced and it is produced at a higher rate than would otherwise happen.”

The findings, Nizkorodov reported, alter understanding of the sources of OH, something that will change how other researchers build computer models that attempt to forecast how air pollution happens.

“It could change air pollution models quite significantly,” Nizkorodov said. “OH is an important oxidant inside water droplets and the main assumption in the models is that OH comes from the air, it’s not produced in the droplet directly.”

To determine whether this new OH production mechanism plays a role, Nizkorodov thinks the next step is to perform carefully designed experiments in the real atmosphere in different parts of the world.

But first, the team expects the results to make a splash in the atmospheric research community.

“A lot of people will read this but will not initially believe it and will either try to reproduce it or try to do experiments to prove it wrong,” said Nizkorodov. “There will be many lab experiments following up on this for sure.”

He added that UCI is a prime place for such science to continue happening, because other labs at UCI, like that of Ann Marie Carlton, professor of chemistry, focus their efforts on the role water droplets play in the atmosphere.

This project, which was funded by the European Research Council, involved researchers from France’s University Claude Bernard, China’s Guangdong University of Technology, and Israel’s Weizmann Institute.

“We found that lonely individuals are exceptionally dissimilar to their peers in the way that they process the world around them … even when taking into account the number of friends that they have,” said lead author Elisa C. Baek (University of Southern California) in an interview. Her study showed that lonely individuals’ neural responses differ from those of other people, suggesting that “seeing the world differently than those around you may be a risk factor for loneliness, even if you regularly socialize with them.”

Baek and colleagues Ryan Hyon, Karina López, Meng Du, Mason A. Porter, and Carolyn Parkinson (University of California, Los Angeles [UCLA]) came to this conclusion by comparing the functional magnetic resonance imaging (fMRI) scans of 63 first-year university students.

During each 90-minute scan, participants viewed 14 engaging video clips in the same order. After the scan, they self-reported their feelings of social connection using the UCLA Loneliness Scale. Earlier in the academic year, each participant had also completed a social network survey in which they were asked to list the names of each person with whom they studied, ate meals, or otherwise hung out during their first several months as students.

In order to analyze these data, Baek and colleagues divided participants into two groups: a “lonely” group with participants who scored higher than the median on the loneliness scale and a nonlonely group with participants who scored under the median.

When the researchers compared these participants’ scans, they found that the brain activity of lonely participants was very dissimilar to that of both nonlonely participants and other lonely participants. By comparison, the brain activity of nonlonely participants was similar to that of other nonlonely participants. This was especially true in the default-mode network, in which shared brain activity appears to be associated with interpreting narratives and friendships in a similar manner, and in the reward-processing areas of the brain, the researchers wrote. These findings remained significant even when the researchers controlled for demographic characteristics and the size of participants’ social networks.

“Lonely people process the world idiosyncratically, which may contribute to the reduced sense of being understood that often accompanies loneliness,” the researchers explained.

Additional research is needed in order to determine the underlying cause of these results, however, Baek said.

“One possibility is that lonely individuals do not find value in the same aspects of situations or scenes as their peers,” Baek and colleagues wrote. “This may result in a reinforcing feedback loop in which lonely individuals perceive themselves to be different from their peers, which may in turn lead to further challenges in achieving social connection.”

Another possibility is that loneliness itself could lead people to process information differently, the researchers added.

In either case, learning more about how lonely people think, and how to promote shared understanding, could help identify new pathways for reducing loneliness, Baek said.

“Copper is one of the most studied and relevant surfaces, both in catalysis and in corrosion science,” explained Anibal Boscoboinik, materials scientist at CFN. “So many mechanical parts that are used in industry are made of copper, so trying to understand this element of the corrosion processes is very important.”

“I’ve always liked looking at copper systems,” said Ashley Head also a materials scientist at CFN. “They have such interesting properties and reactions, some of which are really striking.”

Gaining a better understanding of oxide catalysts gives researchers more control of the chemical reactions they produce, including solutions for clean energy. Copper, for example, can catalytically form and convert methanol into valuable fuels, so being able to control the amount of oxygen and number of electrons on copper is a key step to efficient chemical reactions.

Peroxide as a Proxy

Peroxides are chemical compounds that contain two oxygen atoms linked by shared electrons. The bond in peroxides is fairly weak, allowing other chemicals to alter its structure, which makes them very reactive. In this experiment, scientists were able to alter the redox steps of catalytic oxidation reactions on an oxidized copper surface (CuO) by identifying the makeup of peroxide species formed with different gases: O₂ (oxygen), H₂ (hydrogen), and CO (carbon monoxide).

Redox is a combination of reduction and oxidation. In this process, the oxidizing agent gains an electron and the reducing agent loses an electron. When comparing these different peroxide species and how these steps played out, researchers found that a surface layer of peroxide significantly enhanced CuO reducibility in favor of H₂ oxidation. They also found that, on the other hand, it acted as an inhibitor to suppress CuO reduction against CO (carbon monoxide) oxidation. They found that this opposite effect of the peroxide on the two oxidation reactions stems from the modification of the surface sites where the reaction takes place.

By finding these bonding sites and learning how they promote or inhibit oxidation, scientists can use these gases to gain more control of how these reactions play out. In order to tune these reactions though, scientists had to get a clear look at what was happening.

The Right Tools for the Job

Studying this reaction in situ was important to the team, since peroxides are very reactive and these changes happen fast. Without the right tools or environment, it’s hard to catch such a limited moment on the surface.

Peroxide species on copper surfaces were never observed using in-situ infrared (IR) spectroscopy in the past. With this technique, researchers use infrared radiation to get a better understanding of a material’s chemical properties by looking at the way the radiation is absorbed or reflected under reaction conditions. In this experiment, scientists were able to differentiate “species” of peroxide, with very slight variations in the oxygen they were carrying, which would have otherwise been very hard to identify on a metal oxide surface.

“I got really excited when I was looking up the infrared spectra of these peroxide species on a surface and seeing that there weren’t many publications. It was exciting that we could see these differences using a technique that’s not widely applied to these kind of species,” recalled Head.

IR spectroscopy on its own wasn’t enough to be sure though, which is why the team also used another spectroscopy technique called ambient pressure X-ray Photoelectron Spectroscopy (XPS). XPS uses lower energy x-rays to kick electrons out of the sample. The energy of these electrons gives scientists clues about the chemical properties of atoms in the sample. Having both techniques available through the CFN User Program was key to making this research possible.

“One of the things that we pride ourselves in is the instruments that we have and modified here,” said Boscoboinik. “Our instruments are connected, so users can move the sample in a controlled environment between these two techniques and study them in situ to get complementary information. In most other circumstances, a user would have to take the sample out to go to a different instrument, and that change of environment could alter its surface.”

“A nice feature of CFN lies not only in its state-of-the-art facilities for science, but also the opportunities it provides to train young researchers,” said Guangwen Zhou professor at the Thomas J. Watson College of Engineering and Applied Science’s Department of Mechanical Engineering and the Materials Science program at Binghamton University. “Each of the students involved have benefited from extensive, hands-on experience in the microscopy and spectroscopy tools available at CFN.”

This work was accomplished with the contributions of four PhD students in Zhou’s group: Yaguang Zhu and Jianyu Wang, the first co-authors of this paper, and Shyam Patel and Chaoran Li. All of these students are early in their career, having just earned their PhDs in 2022.

Future Findings

The results of this study may apply to other types of reactions and other catalysts besides copper. These findings and the processes and techniques that led scientists there could find their ways into related research. Metal oxides are widely used as catalysts themselves or components in catalysts. Tuning peroxide formation on other oxides could be a way to block or enhance surface reactions during other catalytic processes.

“I’m involved in some other projects related to copper and copper oxides, including transforming carbon dioxide to methanol to use as a fuel for clean energy,” said Head. “Looking at these peroxides on the same surface that I use has the potential to make an impact on other projects using copper and other metal oxides.”

The research, published this week in JAMA Network Open, compared magnetic resonance imaging (MRI) brain scans of older adults who had high blood pressure between the ages of 30 to 40 with older adults who had normal blood pressure.

The researchers found that the high blood pressure group had significantly lower regional brain volumes and worse white matter integrity. Both factors are associated with dementia.

The research also showed that the negative brain changes in some regions — such as decreased grey matter volume and frontal cortex volume — were stronger in men. They note the differences may be related to the protective benefits of estrogen before menopause.

“Treatment for dementia is extremely limited, so identifying modifiable risk and protective factors over the life course is key to reducing disease burden,” said first author Kristen M. George, an assistant professor in the Department of Public Health Sciences.

“High blood pressure is an incredibly common and treatable risk factor associated with dementia. This study indicates hypertension status in early adulthood is important for brain health decades later,” George said.

High blood pressure prevalent in U.S.

High blood pressure, also known as hypertension, is blood pressure that is higher than normal. A normal blood pressure level is less than 130/80 mmHg. The Centers for Disease Control and Prevention estimates that 47% of adults in the United States have hypertension.

The rate of high blood pressure varies by sex and race. About 50% of men have high blood pressure compared to 44% of women. The rate of hypertension is about 56% in Black adults, 48% in white adults, 46% in Asian adults and 39% in Hispanic adults. African Americans ages 35 to 64 years are 50% more likely to have high blood pressure than whites.

Data from healthy aging studies

The researchers looked at data from 427 participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the Study of Healthy Aging in African Americans (STAR). This provided them with health data from 1964 to 1985 for a diverse cohort of older Asian, Black, Latino and white adults.

They obtained two blood pressure readings from when the participants were between the ages of 30 to 40. This allowed them to determine if they had been hypertensive, transitioning to hypertensive or had normal blood pressure in young adulthood.

MRI scans of the participants conducted between 2017 and 2022 allowed them to look for late-life neuroimaging biomarkers of neurodegeneration and white matter integrity.

A significant reduction in cerebral gray matter volume is seen in both men and women with hypertension but is stronger in men.

Brain scans reveal differences

Compared to participants with normal blood pressure, the brain scans of those transitioning to high blood pressure or with high blood pressure showed lower cerebral gray matter volume, frontal cortex volume and fractional anisotropy (a measure of brain connectivity). The scores for men with high blood pressure were lower than those for women.

The study joins a growing body of evidence that cardiovascular risk factors in young adulthood are detrimental to late-life brain health.

The researchers note that due to the sample size, they could not examine racial and ethnic differences and recommended interpreting results regarding sex differences with caution. They also note that the MRI data was only available from one time-point late in life. This can only determine physical properties like volumetric differences, not specific evidence of neurodegeneration over time.

“This study truly demonstrates the importance of early life risk factors, and that to age well, you need to take care of yourself throughout life — heart health is brain health,” said Rachel Whitmer, senior author of the study. Whitmer is a professor in the departments of Public Health Sciences and Neurology and chief of the Division of Epidemiology. She’s also the associate director of the UC Davis Alzheimer’s Disease Center.

“We are excited to be able to continue following these participants and to uncover more about what one can do in early life to set yourself up for healthy brain aging in late life,” Whitmer said.

Additional authors of the study include Pauline Maillard, Evan Fletcher, Dan M. Mungas and Charles DeCarli, UC Davis; Paola Gilsanz, Kaiser Permanente Division of Research; Rachel L. Peterson, University of Montana, Missoula; Joseph Fong and Elizabeth Rose Mayeda from UCLA; L. Barnes from Rush Medical College; M. Maria Glymour from UCSF.

The study, led by senior author Anthony R. Flores, MD, PhD, MPH, associate professor and chief of pediatric infectious diseases at McGovern Medical School at UTHealth Houston, was published this month in Clinical Infectious Diseases.

During the COVID-19 pandemic, the rate of other infectious diseases dropped due to safety measures such as social distancing and mask-wearing, according to researchers. But as those safety measures began to lift, diseases such as respiratory syncytial virus, the flu, and group A strep all experienced a resurgence in cases.

Infectious disease experts first noticed the rise in cases in the UK, now with 355 deaths of which 40 were children dying from severe group A strep infections. Researchers such as Flores then turned to what was occurring in the U.S.

“In 2020 and 2021, the overall number of infections that we saw due to group A strep were far lower than what we had seen before the pandemic,” Flores said. “When we look at the number of infections by quarter, historically, pre-pandemic cases of group A strep were pretty consistent from quarter to quarter with a little variation and more infections in the winter months. But during the last quarter of 2022, the number of infections we saw, including invasive infections, were far greater than what we’d ever seen before.”

In 2022, a total of 318 individual group A strep cases were identified in young children in Houston. Researchers looked at three group A strep disease types: invasive group A strep (iGAS), skin and soft tissue infections (SSTI), and pharyngeal, or throat, infections (PHG). The study found that group A strep strains derived from iGAS accounted for 31.4%, SSTI for 17.6%, and pharyngeal for 50.9%.

“Proportionately speaking, if we just looked at the percentage of all infections that were invasive, it was the same as we had seen in the past,” Flores said. “It wasn’t like, all of a sudden, 75% of our cases are invasive diseases. What we’re seeing is an increase in the total number of infections.”

The study also found that emm12 group A strep strains were disproportionately represented, compared to emm1 group A strep, which was the dominant emm type pre-pandemic. Emm type is a marker that differentiates different strains of group A strep.

“By looking at the molecular epidemiology, we can look at specific things about the bacteria that give us clues as to whether or not something is changing,” Flores said. “What we will be observing as we go forward is whether it will shift back to what it was pre-pandemic, and if it doesn’t, then we hope to have some work underway that is going to tell us why.”

As cases of group A strep continued to be high in the first quarter of 2023 in Houston, the disease is a cause for concern for pediatricians who see children with symptoms of group A strep.

“The reason why this is important is we’re seeing group A strep more frequently than what we have seen in the past, and therefore, if a physician has a child coming in with a sore throat or with a skin infection, we should have a high index of suspicion for group A strep,” Flores said.

Co-authors on the paper from McGovern Medical Schools department of pediatrics infectious diseases division included Aya Aboulhosn, MD; Misu A. Sanson-Iglesias, MD, PhD; Luis Alberto Vega, PhD; and Maria G. Segura, MD.

The Pathogen Problem

Candida auris is a fungus that can cause serious infections, particularly in patients who are immunocompromised, have pre-existing health conditions, are in long-term healthcare settings, or are undergoing treatment with invasive medical devices such as a catheter. Infection prevention and control is challenging because the fungus can grow on both dry and moist surfaces such as furniture, door handles, clothing, and medical equipment in healthcare facilities. It’s also shown resistance to many commonly used surface disinfectants and all three types of antifungal medicines. More than 1 in 3 patients with invasive C. auris infections — which can affect the blood, heart, or brain — dies.

What’s more, Nevada — one of six states with recently high burdens of C. auris — last year experienced outbreaks across multiple healthcare facilities and logged the most U.S. cases of the fungal infection. The Silver State experienced a 16-fold increase from just 24 cases in 2021 to 384 cases in 2022, according to the Centers for Disease Control and Prevention (CDC). Cases have also been reported in dozens of other countries.

What They Found

A research team led by Casey Barber, a UNLV School of Public Health doctoral student and Southern Nevada Water Authority (SNWA) graduate intern, recently published a study in the journal Environmental Science & Technology that analyzed 10 weeks’ worth of wastewater samples from seven Southern Nevada sewersheds.

The scientists detected the genetic material of C. auris in at least one untreated sewage sample from each Southern Nevada wastewater treatment facility and nearly 80% of all untreated sewage samples in the study. The sewersheds serving healthcare facilities involved in the outbreak also showed higher detection frequencies for the fungus. Researchers noted that no fungus was detected in untreated sewage samples from a wastewater treatment facility in Utah, an area with no known C. auris cases at the time. The fungus was not detected in the Las Vegas Wash, which contains treated wastewater effluent, nor in Lake Mead, indicating that there is no sign that C. auris poses a risk to drinking water.

“These results show that wastewater surveillance may help monitor the spread of C. auris and could serve as an early warning system for public health action,” Barber said.

Other Takeaways

The first human case of C. auris was reported in 2009, but it’s become more prevalent in recent years. The fungus is often spread via contaminated surfaces or skin-to-skin contact with infected individuals, including with those who are asymptomatic.

Scientists called the Southern Nevada fungus flare-up — which erupted in August 2021 and has now affected over 30 healthcare facilities — one of the largest recent outbreaks of healthcare-associated C. auris in the U.S. The research team formally launched C. auris-specific monitoring and data collection in late June 2022, as part of a larger ongoing UNLV wastewater surveillance collaboration with SNWA.

In addition to implications for large-scale C. auris detection and prevention, researchers said the study is groundbreaking in its progress towards helping establish new procedures for sewage sample processing, preparation, and analysis to look for C. auris.

Wastewater surveillance, they said, may provide a more accurate estimate of C. auris prevalence than traditional public health surveillance methods, in part because traditional methods may not accurately identify C. auris, leading to delays in targeted intervention measures. The team also anticipates that their previously established approach to monitoring COVID-19 levels in wastewater could be applied to watching for mutations and new strains of C. auris.

“Detection of Candida auris through wastewater surveillance has already prompted expanded screenings in Southern Nevada healthcare facilities in an effort to prevent larger outbreaks,” said SNWA principal research microbiologist Daniel Gerrity. “This demonstrates how wastewater surveillance can be applied to emerging public health threats beyond COVID-19.”