The latest vaping study from Keck School of Medicine of USC shows that, like smoking, the use of e-cigarettes is linked to dysregulation of mitochondrial genes and immune response genes.

Since they hit the market, e-cigarettes have been touted as a safe alternative to tobacco cigarettes for adult smokers. When research began to suggest otherwise, many questioned whether smoking was still to blame for adverse effects, since most vapers are either “dual users” who also smoke cigarettes or have a prior history of smoking.

Now, a team of researchers at the Keck School of Medicine of USC has demonstrated that – independent of the effects of prior smoking – using e-cigarettes is linked to adverse biological changes that can cause disease. The study, published in Scientific Reports, revealed that vapers experience a similar pattern of changes to gene regulation as smokers do, although the changes are more extensive in people who smoke.

“Our study, for the first time, investigates the biological effects of vaping in adult e-cigarette users, while simultaneously accounting for their past smoking exposure,” said Ahmad Besaratinia, Ph.D., corresponding author, and professor of research population and public health sciences at the Keck School of Medicine.  “Our data indicate that vaping, much like smoking, is associated with dysregulation of mitochondrial genes and disruption of molecular pathways involved in immunity and the inflammatory response, which govern health versus disease state.”

Isolating the effects of vaping from smoking

The researchers recruited a diverse group of 82 healthy adults and separated them into three categories: current vapers, with and without a prior history of smoking; people who exclusively smoke cigarettes; and a control group of never-smokers and never-vapers. They conducted comprehensive in-person interviews to get a detailed vaping and smoking history from each participant. The team verified the histories by performing biochemical analyses on the participants’ blood to measure the concentration of cotinine, a breakdown product of nicotine.

Using next-generation sequencing and bioinformatic data analysis, researchers then conducted a genome-wide search for changes in gene regulation in the blood cells of each of the participants. When the normal regulation of genes is disrupted and genes become dysregulated, that dysregulation can interfere with gene function, leading to disease.

For current vapers, they further performed super computational modeling to determine whether the detected gene dysregulation was associated with the intensity and duration of their current vaping or the intensity and duration of their past smoking.

“We found that more than 80% of gene dysregulation in vapers correlated with the intensity and duration of current vaping,” said Besaratinia. “Whereas none of the detected gene dysregulation in vapers correlated to their prior smoking intensity or duration.”

Effects of vaping mirror those of smoking

In previous research, Besaratinia and his team have shown that e-cigarette users develop some of the same cancer-related molecular changes in oral tissue as cigarette smokers. They also discovered vapers had the same kind of cancer-linked chemical changes to their genome as smokers.

In this study, they found that, in both vapers and smokers, mitochondrial genes are preferential targets of gene dysregulation. They also found that vapers and smokers had significant dysregulation of immune response genes. 

Besaratinia says the findings are not only novel and significant, but they are also interrelated since growing evidence shows that mitochondria play a critical role in immunity and inflammation.

“When mitochondria become dysfunctional, they release key molecules,” said Besaratinia. “The released molecules can function as signals for the immune system, triggering an immune response that leads to inflammation, which is not only important for maintaining health but also plays a critical role in the development of various diseases, such as cardiovascular and respiratory diseases, metabolic diseases, and cancer.”

Adults aren’t the only ones vaping. The Centers for Disease Control estimates that more than 2 million middle and high school students in the U.S. report using e-cigarettes. Besaratinia says that this is one of the main reasons why the team’s research is so critical to informing policy around vaping.

“Given the popularity of e-cigarettes among young never-smokers, our findings will be of importance to the regulatory agencies,” said Besaratinia. “To protect public health, these agencies are in urgent need of scientific evidence to inform the regulation of the manufacture, distribution, and marketing of e-cigarettes.”

Next, the team plans to identify and investigate chemicals common to both e-cigarette vapor and cigarette smoke to find out which ones might be causing similar adverse effects in vapers and smokers.

In data gathered and analyzed over 13 years, the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) Physics Frontiers Center (PFC) has found an intriguing low-frequency signal that may be attributable to gravitational waves.

NANOGrav researchers - including a number from West Virginia University's (WVU's) Department of Physics and Astronomy and the Center for Gravitational Waves and Cosmology - measure the times of arrival of radio pulses from exotic stars called pulsars with large radio telescopes, including the Green Bank Telescope (GBT) in Pocahontas County, West Virginia. Pulsars are small, dense stars that rapidly rotate, emitting beamed radio waves, much like a lighthouse. The results from this most recent dataset show perturbations in the arrival times from these pulsars that may indicate the effects of gravitational waves, as reported recently in The Astrophysical Journal Letters. The most likely source of these gravitational waves is the combined signal from all the supermassive black hole pairs at the cores of merged, distant galaxies.

NANOGrav has been able to rule out some effects other than gravitational waves, such as interference from the matter in our own solar system or certain errors in the data collection. These newest findings set up direct detection of gravitational waves as the possible next major step for NANOGrav and other members of the International Pulsar Timing Array (IPTA), a collaboration of researchers using the world's largest radio telescopes.

Dustin Madison, a postdoctoral researcher at WVU, comments "We can't yet say with confidence that what we're seeing is gravitational waves, but if it is, the "signal" makes a lot of sense given what we think we know about supermassive black holes. This was always how this was going to play out...enticing hints of a signal before we would be able to definitively claim a detection. We're on the right track to make that definitive assessment in just a couple of years." Looking to the future, he thinks researchers will then be able to characterize the signal and learn more from it for years and years to come. {module INSIDE STORY} 

Gravitational waves are ripples in space-time caused by the movements of incredibly massive objects, such as black holes orbiting each other or neutron stars colliding. Astronomers cannot observe these waves with a telescope-like they do stars and galaxies. Instead, they measure the effects passing gravitational waves have, namely tiny changes to the precise position of objects - including the position of the Earth itself. Gravitational waves were first detected in 2015 by NSF's Laser Interferometer Gravitational-Wave Observatory (LIGO) by a team including other researchers at WVU. As light from distant objects, gravitational waves are a cosmic messenger signal - one that holds great potential for understanding "dark" objects, like black holes.

NANOGrav chose to study the signals from pulsars because they serve as detectable, dependable Galactic clocks. These small, dense stars spin rapidly, sending pulses of radio waves at precise intervals toward Earth. Pulsars are in fact commonly referred to as the universe's timekeepers, and this unique trait has made them useful for astronomical study.

But gravitational waves can interrupt this observed regularity, as the ripples cause space-time to undergo tiny amounts of stretching and shrinking. Those ripples result in extremely small deviations in the expected times for pulsar signals arriving on Earth. Such deviations indicate that the position of the Earth has shifted slightly. By studying the timing of the regular signals from many pulsars scattered over the sky at the same time, known as a "pulsar timing array," NANOGrav works to detect minute changes in the Earth's position due to gravitational waves stretching and shrinking space-time.

WVU Professor and NANOGrav member, Sarah Burke-Spolaor explains, "This signal is incredibly enticing. It could be that our orchestra is tuning up, hinting that we're about to hear the grand symphony of waves from supermassive black holes that we expect pervades the Universe," Burke-Spolaor reflects. She adds, "If this signal is indeed gravitational waves, future study will offer unique insights into how the biggest black holes and galaxies in our universe form and evolve." {module INSIDE STORY}

"NANOGrav has been building to the first detection of low-frequency gravitational waves for over a decade and today's announcement shows that they are on track to achieving this goal," said Pedro Marronetti, NSF Program Director for gravitational physics. "The insights that we will gain on cosmology and galaxy formation are truly unparalleled."

NANOGrav is a collaboration of U.S. and Canadian astrophysicists and a National Science Foundation Physics Frontiers Center (PFC). Maura McLaughlin, WVU Professor and Co-Director of the NANOGrav PFC, added "We are so grateful for the support of the NANOGrav PFC, that's allowed us to dramatically increase both the number of pulsars being timed and the number of participants working on NANOGrav research over the past six years". WVU has played a significant role in the PFC; 12 of the 63 authors on this paper are WVU faculty, postdocs, and students. And low-frequency gravitational wave detection is one of the main aims of the Center for Gravitational Waves and Cosmology, formed in 2015 along with the award of the PFC. As, Duncan Lorimer, WVU Professor and Eberly College Associate Dean for Research, notes "The long-term institutional support provided by the College and University has played a critical role in NANOGrav's success since its inception in 2007".

NANOGrav created their pulsar timing array by studying 47 of the most stably rotating "millisecond pulsars" with both the GBT and the Arecibo Observatory in Puerto Rico as reported in the January 2021 Astrophysical Journal Supplements. Not all pulsars can be used to detect the signals that NANOGrav seeks - only the most stably rotating and longest-studied pulsars will do. These pulsars spin hundreds of times a second, with incredible stability, which is necessary to obtain the precision required to detect and study gravitational waves.

Of the 47 pulsars studied, 45 had sufficiently long datasets of at least three years to use for the analysis. Researchers studying the data uncovered a spectral signature, a low-frequency noise feature, that is the same across multiple pulsars. The timing changes NANOGrav studies are so small that the evidence is not apparent when studying any individual pulsar, but in aggregate, they add up to a significant signature.

Potential Next Steps

To confirm direct detection of a signature from gravitational waves, NANOGrav's researchers will have to find a distinctive pattern in the signals between individual pulsars. At this point, the sensitivity of the experiment is not currently good enough for such a pattern to be distinguishable. Boosting the signal requires NANOGrav to expand its dataset to include more pulsars studied for even longer lengths of time, which will increase the array's sensitivity. In addition, by pooling NANOGrav's data together with those from other pulsar timing array experiments, a joint effort by the IPTA may reveal such a pattern. Students and faculty at WVU are important contributors to this effort, and in fact, 24 WVU students have traveled to IPTA partner countries to undertake research abroad as part of NSF-funded programs led by WVU.

At the same time, NANOGrav is developing techniques to ensure the detected signal could not be from another source. They are producing supercomputer simulations that help test whether the detected noise could be caused by effects other than gravitational waves, in order to avoid false detection.

While the next several years hold a great deal of scientific promise, they are not without challenges. With the recent collapse of the Arecibo Observatory's 305-meter telescope, NANOGrav will be seeking alternate sources of data and working even more closely with their international colleagues. Although significant delays in detection are not expected, due to years of very sensitive Arecibo data already contributing to their datasets, the loss of Arecibo is a terrible blow to science in general. For NANOGrav, it may impact the ability to characterize the background and detect other types of gravitational-wave sources in the future in the absence of another instrument. The loss of the telescope also directly impacts the graduate studies of several WVU Ph.D. students. NANOGrav members are deeply saddened by the collapse and its impact on the staff and the island of Puerto Rico.

Publications referenced in this article

Gravitational Wave Search:
https://iopscience.iop.org/article/10.3847/2041-8213/abd401

Narrowband Dataset:
https://iopscience.iop.org/article/10.3847/1538-4365/abc6a0

Wideband Dataset:
https://iopscience.iop.org/article/10.3847/1538-4365/abc6a1

For more information about NANOGrav, please visit the website at http://nanograv.org.