Research roundup

Insights & Outcomes: Foreign DNA, quantum potholes and relapsing fever

This month, we dig into the nitty gritty of quantum singularities, relapsing fever, a drug to reduce drinking, and a panoply of bacterial pathogens.
Quantum pothole illustration


This month, Insights & Outcomes digs into the nitty gritty of quantum potholes, foreign DNA, relapsing fever, and the thermodynamics of hydrogen binding.

As always, you can find more science and medicine research news on Yale News’ Science & Technology and Health & Medicine pages.

Looking for quantum potholes

In some quantum mechanical systems, researchers say, the energy landscape is going to have a few “potholes” — touching points where the state of the system is not defined. Understanding how these potholes, known as singularities, affect a quantum system’s behavior is a key area of physics research.

In a new study in the journal Science, incoming Yale assistant professor of physics Charles D. Brown II and his collaborators found a new approach for probing certain types of quantum singularities.

For the study, Brown and co-authors from the University of California-Berkeley conducted a unique quantum simulation experiment with intersecting lasers that trap and manipulate ultra-cold atoms in crystals made of light. The researchers moved the atoms along trajectories that entered, turned, and exited singularities at linear touching points (called Dirac points) and quadratic touching points.

A quadratic band touching point is a point at which two energy bands have equal values — but away from this point the energy values are non-equal, and the gap between the energy bands grows proportional to the square of the distance from the point. 

The researchers found that the ultimate state of the system depended only on the entry and exit angles through the singularities.

We developed a distinct method to probe singularities, importantly including non-Dirac singularities, in ultracold atom quantum simulators,” Brown said.

Brown is first author and co-corresponding author of the study. Dan Stamper-Kurn of the University of California-Berkeley is the senior and co-corresponding author.

The hijacking of molecule CD55

Relapsing fever, a condition caused by bacterial infections transmitted by lice or tick bites, is characterized by recurrent bouts of fever, headache, and muscle aches. If left untreated, it can cause severe disability and even death.

Yet the condition — which often afflicts people living in poorer regions of Africa, central Asia, and Central and South America — remains a relatively unstudied disease.

In a new study, a team of Yale researchers analyzed different species of Borellia bacteria that cause many cases of relapsing fever and Lyme disease in humans, identifying a single molecule that allows two species of Borrelia to avoid immune system detection. They found that mice infected with relapsing fever but lacking the molecule CD55 had lower levels of the pathogen and a bolstered immune response.

While CD55 normally acts as a regulator of immune system response to protect potentially damaging response to host tissues, in cases of relapsing fever it is hijacked by bacteria to avoid detection and eradication, explained co-lead author Gunjan Arora, associate research scientist in the lab of senior author Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases) and Professor of Epidemiology (Microbial Diseases) and of Microbial Pathogenesis. “The pathogens got very smart and used a molecule designed to balance our immune system response to survive in the host,” Arora said.

Geoffrey Lynn, associate research scientist, is co-lead author of the study published in the journal mBio.

The ties that bind hydrogen

For decades, researchers studying the conversion of light energy into electrical or chemical energy — such as in solar cells — have focused on the movement of electrons, which are central to the process.

But in a new study in the journal Chem, Yale chemists James Mayer and Hyunho Noh take a different approach. They looked at energy conversion reactions as a type of “whole atom” transfer of hydrogen atoms, which have one electron and one proton, and are found in most energy conversion reactions.

For the study, Mayer, the Charlotte Fitch Roberts Professor of Chemistry in Yale’s Faculty of Arts and Sciences, and Noh, a postdoctoral associate in chemistry, measured the thermodynamics of hydrogen-atom binding to nickel oxide electrodes when in contact with three solvents: water, dimethylformamide, and acetonitrile.

Our work shows that the ‘electron-only’ model is not sufficient,” Mayer said. “The other new approach this paper develops is that the solid/solution interface has a range of surface sites, with somewhat different strengths of chemical bonds. While this range of energies is well known in some areas of surface science, the importance of this effort has not been emphasized.”

They found that the binding of hydrogen was the same no matter which solvent they used or what was dissolved in the solution, showing that this parameter is the best intrinsic property of the electrode, while the electron-only parameters vary strongly with the nature of the medium.

Heart failure drug may help reduce ‘problem drinking’

A medication commonly used to treat heart failure may also reduce alcohol drinking, especially among those diagnosed with alcohol use disorder, researchers from Yale School of Medicine and the National Institutes of Health Intramural Research Program (NIH IRP) report.

The effects of the drug spironolactone on drinking behavior in mice, rats, and humans were reported in the journal Molecular Psychiatry.

This is a remarkable example of bench to bedside team science showing that an inexpensive, off-patent drug, may help reduce alcohol consumption,” said co-senior author Amy Justice, the C.N.H. Long Professor of Medicine and professor of public health.

In animal models of excessive alcohol drinking, researchers from the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) IRPs found that when administered to rats and mice, spironolactone reduced consumption of alcohol, and it did so in a dose dependent manner.

The Yale team, headed by Justice, then analyzed data from the U.S. Department of Veterans Affairs to assess the effects of spironolactone taken for at least 60 days on individuals reporting current alcohol use. Compared to similar individuals who did not receive the drug, those who took spironolactone reported greater decreases in alcohol consumption, the researchers found.

And those who had more severe alcohol problems, particularly those diagnosed with alcohol use disorder, benefitted the most,” Justice said.

There are limited number of drugs that can help reduce harmful alcohol consumption, which costs the U.S. healthcare system $28 billion annually and another $179 billion in lost productivity, according to the Centers for Disease Control and Prevention.

Spironolactone is a medication in widespread use and a proven safety profile that is no longer on patent offering a ready additional tool to treat alcohol use disorder, the authors said.

All together, our findings provide strong justification for randomized clinical trials to further investigate the potential of this medication in patients with alcohol use disorder,” said co-first author Christopher Rentsch, assistant professor at the Yale School of Medicine and London School of Hygiene & Tropical Medicine.

Lorenzo Leggio of the NIDA and NIAAA IRPs and Leandro Vendruscolo of the NIDA IRP are co-senior authors.

Bringing species expertise to agricultural policy

Yale scientist Emily Sandall will spend a year with the Office of Trade Policy & Geographic Affairs in the U.S. Department of Agriculture as a recipient of the American Association for the Advancement of Science’s Science & Technology Policy Fellowship.

Sandall is a postdoctoral researcher in the Department of Ecology and Evolutionary Biology, in Yale’s Faculty of Arts and Sciences.

Her research has focused primarily on insect biodiversity patterns, through geographic, morphological, and phylogenetic methods. As a postdoctoral research associate in the Yale Center for Biodiversity & Global Change, she examined global dragonfly biogeography and led a team of species experts. In her fellowship role, her research background in insect biodiversity, taxonomy, natural history, and data standards will enable her to share expertise on topics related to agricultural policy throughout the U.S. government, including species-level protections or restrictions. For instance, on topics related to an endangered or invasive species, she will be able to provide critical insights into scientific literature about how that affects trade agreements and provide summaries to negotiators and policymakers to inform their decisions.

Some facts about foreign genes

Foreign DNA, or genetic material that comes from an organism of the same or different species, is key to the survival of bacteria, helping them resist antimicrobial agents and adapt to a variety of changing environments. Bacterial pathogens also often rely on foreign genes to cause disease in humans. But how do bacteria know which foreign genes to accept?

To answer this question, researchers in the lab of Eduardo Groisman, the Waldemar Von Zedtwitz Professor of Microbial Pathogenesis, zeroed in on the role of a widespread protein known to prevent the expression of foreign DNA. In doing so, they solved the question of how bacteria can overcome foreign gene silencing to access the benefits of foreign DNA.

Specifically, the researchers explored how bacteria can express genes otherwise suppressed by the foreign gene silencing protein H-NS. Because H-NS amounts were believed to remain constant, researchers had ascribed the overcoming of foreign gene silencing to other proteins. In the new study, however, Jeongjoon Choi, an associate research scientist, and Groisman found that the human pathogen Salmonella Typhimurium degrades H-NS when inside a mammalian host — and they identified the enzyme responsible for H-NS degradation.

According to their findings, the researchers identified a mutant form of H-NS that resists degradation and found that the beneficial bacterium Escherichia coli cannot express foreign genes or colonize the gut of mice when it harbors the mutant H-NS.

The researchers demonstrated that H-NS degradation is essential for different bacterial species to express foreign genes, showing that beneficial E. coli and pathogenic Salmonella both use the same strategy to overcome gene silencing and thus adapt to the specific environments they face during infection. The research was published in the Proceedings of the National Academy of Sciences.

Research Redux:

Creating new neuropsychiatric drug candidates — from a virtual library

Study finds all African carnivores at risk for range loss

Yale’s Spielman wins $3 million Breakthrough Prize

The roots of biodiversity: how proteins differ across species

Jumping’ genes yield new clues to origins of neurodegenerative disease

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