Insights & Outcomes: Biofilms, cravings, and cells that spill their guts
This month, Insights & Outcomes offers an all-star roster of the latest Yale research on the role cravings play in addiction, an innovative way to predict El Niño, a particular type of white blood cell that spills its guts, and the bacterial coatings known as biofilms.
Studying the biofilms
Colonies of bacteria collaborate to form biofilms, which are slimy protective coats that protect them against environmental threats, such as immune defenses and antibiotics. However, bacterial cells pay a cost for this protection. The cells must collectively produce and secrete glue-like adhesion proteins outside of the cell to create the elaborate biofilm matrix.
Yale researchers were curious how biofilm-creating bacteria protect themselves against molecular free-loaders, or cheater cells, which derive benefits from biofilms but contribute nothing to their creation. In theory these free-loading, exploitative cells should outcompete biofilm-creating peers for survival.
For an answer, a team of researchers led by Jung-Shen “Benny” Tai — who is in the lab of Jing Yan, assistant professor of molecular, cellular and developmental biology — studied biofilms formed during cholera, a waterborne, intestinal infection that leads to sometimes fatal bouts of acute diarrhea. “We wanted to know how these colonies punish the bad guys that benefit from public good without benefitting the community,” Yan said.
They found that biofilm-creating proteins maintain a sort of social distance from cheater cells, which minimizes protection for the exploitive cells. They also found that in real-life conditions, environmental factors that increase flow — in the case of cholera conditions such as diarrhea — tend to limit benefits to cells that do not contribute adhesion molecules to the creation of biofilms.
Yan and his team want to know how to interfere with adhesive properties of harmful biofilms to combat infection and antibiotic resistance in a host of diseases. But they are also studying how strengthening adhesion properties within biofilms might lead to better waterproof glue, which could be valuable in a host of industrial applications. Carey Nadell from Dartmouth and Jeff Tithof at the University of Minnesota are co-authors of the study. They reported their findings in the journal Proceedings of the National Academy of Sciences.
A hybrid approach to predicting El Niño
A Yale-led study has produced an innovative way to predict the El Niño Southern Oscillation (ENSO) — the largest interannual variability process in Earth’s climate — by using limited data to reveal hidden features.
The warm phase of ENSO is called El Niño, a phenomenon that, while driven by the air-sea interactions in the tropical Pacific Ocean, affects weather, crops, and public safety across much of the planet. Therefore, accurate estimates of ENSO are crucial to predicting a wide range of regional and global climate events.
There are two traditional methods that scientists use to model ENSO: state-of-the-art, coupled general circulation models (GCMs), and low-order statistical models, which rely on observed statistics. GCMs provide better representations of air-sea interactions in the tropical Pacific, while statistical models are able to characterize the large-scale features of ENSO and require less computational assistance.
In a new study in the journal Physical Review Research, John Wettlaufer, Yale’s A.M. Bateman Professor of Geophysics, Mathematics, and Physics, and his colleagues, offer a different approach.
“We have developed a stochastic theory that reproduces the large-scale dynamical and statistical characteristics of ENSO,” Wettlaufer said. “By harnessing a confluence of modern applied mathematical methods and physical modeling, our approach incorporates only a subset of observations from which we infer unobserved quantities, such as the depth of the ocean thermocline and the wind bursts on the ocean surface.”
The hybrid method eliminates the need to run large, numerical models or search through every bit of available data, the researchers said.
The other authors of the study are first author Ludovico Giorgini and Woosok Moon of the Nordic Institute for Theoretical Physics in Stockholm, and Nan Chen of the University of Wisconsin-Madison.
A NET gets caught
Neutrophils are a type of white blood cell that are critical for immune system function. One way they protect the body is by ejecting sticky masses called neutrophil extracellular traps, or NETs, which ensnare dangerous invaders like bacteria and viruses. “When neutrophils become activated, some of them spill their guts, their DNA, and create this huge net that’s really sticky,” said James Hansen, associate professor of therapeutic radiology. NETs are important for health but if neutrophils go overboard and spill their guts too often, they can actually contribute to inflammatory diseases like cystic fibrosis, cancer, COVID-19, and more. Being able to calm neutrophils and rein in NETs could help treat these diseases.
In a study recently published in the journal ImmunoHorizons, Hansen and his colleagues found that a certain lupus antibody can do just that. Lupus is an autoimmune disease. One of its hallmarks is an abundance of antibodies that bind DNA; some can get through cell membranes, enter the body’s own cells, and mess with DNA repair processes. Antibodies of this sort are currently being studied as potential treatments for cancer, but Hansen wanted to see if they could affect neutrophils and other inflammatory diseases, too. His team found that the lupus antibody prevented neutrophils from releasing NETs.
“Butterflies are the international symbol for lupus, so this finding sort of flips the script,” said Hansen. “Here, it’s the butterfly that catches the NET.”
More research is needed to understand what effect this antibody might have on inflammatory disease, but Hansen said the findings are promising and, in the future, it’s possible this antibody could be paired with typical anti-inflammatory drugs to better treat diseases where inflammation has gone awry.
Cravings and cues are crucial
A meta-analysis of 237 studies representing 51,788 participants shows conclusively that both exposure to drug and alcohol cues — such as pictures of drugs, paraphernalia, or seeing someone using drugs — and the magnitude of craving can be used to predict drug use and relapse. This suggests that both cues and cravings can defeat efforts to treat substance use disorders, Yale researchers report.
Indeed, even a small increase in craving or a brief exposure to these cues — in addition to increased stress — can double the odds of future drug use or relapse, the meta-analysis shows.
Understanding the role of cues and cravings is crucial for the treatment of addiction, which is associated with 11.8 million deaths annually (or one in five deaths) and costs a staggering $740 billion every year in the United States alone.
“These sobering statistics underscore the urgent need to identify reliable predictors of drug use and relapse in order to improve diagnosis, tracking, and treatment,” said Yale’s Hedy Kober, associate professor of psychiatry and psychology and senior author of the paper.
Kober said that despite the inclusion of craving as a defining feature of substance abuse disorder in “The Diagnostic and Statistical Manual of Mental Disorders,” which is published by the American Psychiatric Association, many doctors are either unaware of the impact of craving and cues or doubt their importance.
Hopefully, Kober said, this comprehensive meta-analysis will help reinforce the importance of assessing cue exposure and measuring craving in treatment. She further recommended that craving be measured frequently, and as early as during primary care treatment, to assess the likelihood of drug use and relapse.
The study was published in the journal JAMA Psychiatry.