‘Jumping genes’ help stabilize DNA folding patterns

“Jumping genes” — bits of DNA that can move from one spot in the genome to another — are well-known for increasing genetic diversity over the long course of evolution. Now, new research at Washington University School of Medicine in St. Louis indicates that such genes, also called transposable elements, play another, more surprising role: stabilizing the 3D folding patterns of the DNA molecule inside the cell’s nucleus.

The study appears Jan. 24 in the journal Genome Biology.

The DNA molecule inside the nucleus of any human cell is more than six feet long. To fit into such a small space, it must fold into precise loops that also govern how genes are turned on or off. It might seem counterintuitive that bits of DNA that randomly move about the genome can provide stability to these folding patterns. Indeed, the discovery contradicts a long-held assumption that the precise order of letters in the DNA sequence always dictates the broader structure of the DNA molecule.

“In places where the larger 3D folding of the genome is the same between mice and humans, you expect the sequence of the letters of the DNA anchoring that shape to be conserved there as well,” said senior author Ting Wang, PhD, the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine. “But that’s not what we found, at least not in the portions of the genome that in the past have been called ‘junk DNA.'”

Studying DNA folding in mouse and human blood cells, the researchers found that in many regions where the folding patterns of DNA are conserved through evolution, the genetic sequence of the DNA letters establishing these folds is not. It is ever so slightly displaced. But this changing sequence, a genetic turnover, doesn’t cause problems. Because the structure largely stays the same, the function presumably does, too, so nothing of importance changes.

“We were surprised to find that some young transposable elements serve to maintain old structures,” said first author Mayank N.K. Choudhary, a doctoral student in Wang’s lab. “The specific sequence may be different, but the function stays the same. And we see that this has happened multiple times over the past 80 million years, when the common ancestors of mice and humans first diverged from one another.”

The fact that a new transposable element can insert itself and serve the same role as an existing anchor creates a redundancy in the regulatory portions of the genome — regions of the DNA molecule that determine how and when genes are turned on or off.

According to the researchers, this redundancy makes the genome more resilient. In providing both novelty and stability, jumping genes may help the mammalian genome strike a vital balance — allowing animals the flexibility to adapt to a changing climate, for example, while preserving biological functions required for life, protecting against the DNA damage that is wrought by living and reproducing on Earth over the span of deep time, measured in tens to hundreds of millions of years.

Even so, the researchers were careful to distinguish between portions of the genome that hold genes responsible for producing proteins and the rest of the genome. In genes that code for proteins, the genetic sequence and the structure are both conserved, and this study does not contradict that. However, the new research suggests that jumping genes in the non-protein coding areas of the genome follow different rules of conservation than the protein-coding genes.

“Our study changes how we interpret genetic variation in the noncoding regions of the DNA,” Wang said. “For example, large surveys of genomes from many people have identified a lot of variations in noncoding regions that don’t seem to have any effect on gene regulation, which has been puzzling. But it makes more sense in light of our new understanding of transposable elements — while the local sequence can change, but the function stays the same.

“We may need to revisit these types of studies in light of the new understanding we now have of transposable elements,” he added. “We have uncovered another layer of complexity in the genome sequence that was not known before.”

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Materials provided by Washington University School of Medicine. Original written by Julia Evangelou Strait. Note: Content may be edited for style and length.

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Blue-emitting diode demonstrates limitations and promise of perovskite semiconductors

University of California, Berkeley, scientists have created a blue light-emitting diode (LED) from a trendy new semiconductor material, halide perovskite, overcoming a major barrier to employing these cheap, easy-to-make materials in electronic devices.

In the process, however, the researchers discovered a fundamental property of halide perovskites that may prove a barrier to their widespread use as solar cells and transistors.

Alternatively, this unique property may open up a whole new world for perovskites far beyond that of today’s standard semiconductors.

In a paper appearing Jan. 24 in the journal Science Advances, UC Berkeley chemist Peidong Yang and his colleagues show that the crystal structure of the halide perovskites changes with temperature, humidity and the chemical environment, disrupting their optical and electronic properties. Without close control of the physical and chemical environment, perovskite devices are inherently unstable. This is not a major problem for traditional semiconductors.

“Some people may say this is a limitation. For me, this is a great opportunity,” said Yang, the S. K. and Angela Chan Distinguished Chair in Energy in the College of Chemistry and director of the Kavli Energy NanoSciences Institute. “This is new physics: a new class of semiconductors that can be readily reconfigured, depending on what sort of environment you put them in. They could be a really good sensor, maybe a really good photoconductor, because they will be very sensitive in their response to light and chemicals.”

Current semiconductors made of silicon or gallium nitride are very stable over a range of temperatures, primarily because their crystal structures are held together by strong covalent bonds. Halide perovskite crystals are held together by weaker ionic bonds, like those in a salt crystal. This means they’re easier to make — they can be evaporated out of a simple solution — but also susceptible to humidity, heat and other environmental conditions.

“This paper is not just about showing off that we made this blue LED,” said Yang, who is a senior faculty scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and a UC Berkeley professor of materials science and engineering. “We are also telling people that we really need to pay attention to the structural evolution of perovskites during the device operation, any time you drive these perovskites with an electrical current, whether it is an LED, a solar cell or a transistor. This is an intrinsic property of this new class of semiconductor and affects any potential optoelectronic device in the future using this class of material.”

The blue diode blues

Making semiconductor diodes that emit blue light has always been a challenge, Yang said. The 2014 Nobel Prize for Physics was awarded for the breakthrough creation of efficient blue light-emitting diodes from gallium nitride. Diodes, which emit light when an electric current flows through them, are optoelectronic components in fiber optic circuits as well as general purpose LED lights.

Since halide perovskites first drew wide attention in 2009, when Japanese scientists discovered that they make highly efficient solar cells, these easily made, inexpensive crystals have excited researchers. So far, red- and green-emitting diodes have been demonstrated, but not blue. Halide perovskite blue-emitting diodes have been unstable — that is, their color shifts to longer, redder wavelengths with use.

As Yang and his colleagues discovered, this is due to the unique nature of perovskites’ crystal structure. Halide perovskites are composed of a metal, such as lead or tin, equal numbers of larger atoms, such as cesium, and three times the number of halide atoms, such as chlorine, bromine or iodine.

When these elements are mixed together in solution and then dried, the atoms assemble into a crystal, just as salt crystalizes from sea water. Using a new technique and the ingredients cesium, lead and bromine, the UC Berkeley and Berkeley Lab chemists created perovskite crystals that emit blue light and then bombarded them with X-rays at the Stanford Linear Accelerator Center (SLAC) to determine their crystalline structure at various temperatures. They found that, when heated from room temperature (about 300 Kelvin) to around 450 Kelvin, a common operating temperature for semiconductors, the crystal’s squashed structure expanded and eventually sprang into a new orthorhombic or tetragonal configuration.

Since the light emitted by these crystals depends on the arrangement of and distances between atoms, the color changed with temperature, as well. A perovskite crystal that emitted blue light (450 nanometers wavelength) at 300 Kelvin suddenly emitted blue-green light at 450 Kelvin.

Yang attributes perovskites’ flexible crystal structure to the weaker ionic bonds typical of halide atoms. Naturally occurring mineral perovskite incorporates oxygen instead of halides, producing a very stable mineral. Silicon-based and gallium nitride semiconductors are similarly stable because the atoms are linked by strong covalent bonds.

Making blue-emitting perovskites

According to Yang, blue-emitting perovskite diodes have been hard to create because the standard technique of growing the crystals as a thin film encourages formation of mixed crystal structures, each of which emits at a different wavelength. Electrons get funneled down to those crystals with the smallest bandgap — that is, the smallest range of unallowed energies — before emitting light, which tends to be red.

To avoid this, Yang’s postdoctoral fellows and co-first authors — Hong Chen, Jia Lin and Joohoon Kang — grew single, layered crystals of perovskite and, adapting a low-tech method for creating graphene, used tape to peel off a single layer of uniform perovskite. When incorporated into a circuit and zapped with electricity, the perovskite glowed blue. The actual blue wavelength varied with the number of layers of octahedral perovskite crystals, which are separated from one another by a layer of organic molecules that allows easy separation of perovskite layers and also protects the surface.

Nevertheless, the SLAC experiments showed that the blue-emitting perovskites changed their emission colors with temperature. This property can have interesting applications, Yang said. Two years ago, he demonstrated a window made of halide perovskite that becomes dark in the sun and transparent when the sun goes down and also produces photovoltaic energy.

“We need to think in different ways of using this class of semiconductor,” he said. “We should not put halide perovskites into the same application environment as a traditional covalent semiconductor, like silicon. We need to realize that this class of material has intrinsic structural properties that make it ready to reconfigure. We should utilize that.”

The work was supported by the U.S. Department of Energy’s Basic Energy Sciences program. Other co-authors of the paper are Qiao Kong, Dylan Lu, Minliang Lai, Li Na Quan and Jianbo Jin of UC Berkeley; Jun Kang, Zhenni Lin and Lin-wang Wang of Berkeley Lab; and Michael Toney of SLAC. Chen is currently at Southern University of Science and Technology in Shenzhen, China; Lin is at Shanghai University of Electric Power; and Joohoon Kang is at Sungkyunkwan University in Seoul, South Korea.

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High air pollution exposure in 1-year-olds linked to structural brain changes at age 12

A new study suggests that significant early childhood exposure to traffic-related air pollution (TRAP) is associated with structural changes in the brain at the age of 12.

The Cincinnati Children’s Hospital Medical Center study found that children with higher levels of TRAP exposure at birth had reductions at age 12 in gray matter volume and cortical thickness as compared to children with lower levels of exposure.

“The results of this study, though exploratory, suggest that where you live and the air you breathe can affect how your brain develops, says Travis Beckwith, PhD, a research fellow at Cincinnati Children’s and lead author of the study. “While the percentage of loss is far less than what might be seen in a degenerative disease state, this loss may be enough to influence the development of various physical and mental processes.”

Gray matter includes regions of the brain involved in motor control as well as sensory perception, such as seeing and hearing. Cortical thickness reflects the outer gray matter depth. The study found that specific regions in the frontal and parietal lobes and the cerebellum were affected with decreases on the order of 3 to 4 percent.

“If early life TRAP exposure irreversibly harms brain development, structural consequences could persist regardless of the time point for a subsequent examination,” says Dr. Beckwith.

The researchers on the study, which is published online in PLOS One, used magnetic resonance imaging to obtain anatomical brain images from 147 12 year olds. These children are a subset of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), which recruited volunteers prior to the age of six months to examine early childhood exposure to TRAP and health outcomes.

The volunteers in the CCAAPS had either high or low levels of TRAP exposure during their first year of life. The researchers estimated exposure using an air sampling network of 27 sites in the Cincinnati area, and 24/7 sampling was conducted simultaneously at four or five sites over different seasons. Participating children and their caregivers completed clinic visits at ages 1, 2, 3, 4, 7 and 12.

Previous studies of TRAP suggest that it contributes to neurodegenerative diseases and neurodevelopmental disorders. This work supports that TRAP changes brain structure early in life.

Senior author of the study is Kim Cecil, PhD, a scientist at the Cincinnati Children’s Imaging Research Center.

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Materials provided by Cincinnati Children’s Hospital Medical Center. Note: Content may be edited for style and length.

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Going with the flow: New insights into mysterious fluid motions

Water issuing from an ordinary faucet tells a complex tale of its journey through a pipe. At high velocities, the faucet’s gushing stream is turbulent: chaotic, disorderly — like the crash of ocean waves.

Compared to orderly laminar flows, like the faucet’s steady stream at low velocities, scientists know little about turbulence. Even less is known about how laminar flows become turbulent. A mix of orderly and disorderly flows, transitional flows occur when fluids move at intermediate velocities.

Now, Dr. Rory Cerbus, Dr. Chien-chia Liu, Dr. Gustavo Gioia, and Dr. Pinaki Chakraborty, researchers in the Fluid Mechanics Unit and the Continuum Physics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), have drawn from a decades-old conceptual theory of turbulence to develop a new approach for studying transitional flows. The scientists’ findings, published in Science Advances, may help furnish a more comprehensive, conceptual understanding of transitional and turbulent flows, with practical applications in engineering.

“Turbulence is often touted as the last unsolved problem in classical physics — it has a certain mystique about it,” said Cerbus. “And yet, under idealized conditions, we have a conceptual theory that helps explain turbulent flows. In our research, we’re striving to understand if this conceptual theory might also shed light on transitional flows.”

Finding order in disorder

Scientists have long been captivated by turbulent flows. In the fifteenth century, Leonardo da Vinci illustrated turbulent flows as collections of swirling eddies, or circular currents, of varying sizes.

Centuries later in 1941, mathematician Andrey Kolmogorov developed a conceptual theory that revealed order underlying the energetics of seemingly disordered eddies.

As depicted in DaVinci’s sketch, a stream plunging into a pool of water initially forms a large, swirling eddy, which quickly becomes unstable and breaks apart into progressively smaller eddies. Energy is transferred from the large to ever-smaller eddies, until the smallest eddies dissipate the energy via the water’s viscosity.

Capturing this imagery in the language of mathematics, Kolmogorov’s theory predicts the energy spectrum, a function which describes how the kinetic energy — the energy from motion — is apportioned across eddies of different sizes.

Importantly, the theory says that the energetics of the small eddies is universal, meaning that although turbulent flows may look different, the smallest eddies in all turbulent flows have the same energy spectrum.

“That such simple concepts can elegantly elucidate a seemingly intractable problem, I find it truly extraordinary,” said Chakraborty.

But there is a catch. Kolmogorov’s theory is widely thought to apply only to a small set of idealized flows, and not the flows of everyday life, including the transitional flows.

To study these transitional flows, Cerbus and his collaborators conducted experiments on water flowing through a 20-meter-long, 2.5-centimeter-diameter glass cylindrical pipe. The researchers added small, hollow particles with approximately the same density as water, allowing them to visualize the flow. They used a technique called laser doppler velocimetry to measure the velocities of the eddies in the transitional pipe flows. With these measured velocities, they computed the energy spectrum.

Surprisingly, the researchers found that, despite seeming distinct from turbulent flows, the energy spectrum corresponding to the small eddies in the transitional flows conformed to the universal energy spectrum from Kolmogorov’s theory.

Beyond furnishing a new conceptual understanding of transitional flows, this finding has applications in engineering. Over the past two decades, Gioia and Chakraborty’s research has shown that energy spectra can help predict friction between the flow and the pipe — a major concern for engineers. The more friction in a pipe, the more difficult it is to pump and transport fluids like oil.

“Our study combines esoteric mathematical ideas with factors that engineers care about,” said Chakraborty. “And, we’ve found that Kolmogorov’s theories have wider applicability that anyone thought. This is an exciting new insight into turbulence as well as into the transition to turbulence.”

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Early life adversity and opioid addiction

Individuals with a history of early life adversity (ELA) are disproportionately prone to opioid addiction. A new UCI-led study reveals why.

Published in Molecular Psychiatry, the study titled, “On the early life origins of vulnerability to opioid addiction,” examines how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

“We already know that genetics plays a major role in addiction vulnerability. But, this factor alone cannot account for the recent exponential rise in opioid abuse,” said Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study. “Our team was determined to find out if environmental factors, like early life adversity, were contributing.”

Until now, it was unclear whether alterations of the maturation and function of pleasure/reward circuits in the brain, resulting from ELA, actually caused individuals to be more vulnerable to opioid use disorder.

“Our work creates, for the first time, a direct causal link between early life adversity and opioid addiction vulnerability,” said Stephen V. Mahler, an assistant professor in the Department of Neurobiology & Behavior at the UCI School of Biological Sciences and a senior researcher for the study. “This is key to the development of predictive biomarkers and possible prevention strategies aimed at addressing the growing opioid abuse epidemic.”

Prior studies involving rodents demonstrated that ELA is characterized by chaotic, unpredictable maternal signals to the developing pups. Converging evidence from both humans and rodents shows that such unpredictable, fragmented early life environments may lead to abnormal maturation of certain brain circuits, which profoundly impacts brain function and persists into adolescence and adulthood.

For this study, researchers simulated ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time. In female rats, this led to striking opioid addiction-like characteristics including an increased relapse-like behavior. Remarkably, as observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

“Our study provided novel insights into potential origins and nature of a reward circuit malfunction in the brain,” said Baram. “Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin addicted women.”

The findings highlight the importance of attention to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

According to the National Institute on Drug Abuse, more than 130 people in the United States die each day after overdosing on opioids. The misuse of and addiction to opioids — including prescription pain relievers, heroin, and synthetic opioids such as fentanyl — is a serious national crisis that affects public health as well as social and economic welfare. The Centers for Disease Control and Prevention estimates that the total “economic burden” of prescription opioid misuse alone is $78.5 billion a year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement.

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Fonts in campaign communications have liberal or conservative leanings

“I was driving through the region and noticed the same campaign was using a different font on signs in rural areas than on the signs in town,” said Haenschen, an assistant professor in the Department of Communication. “I thought, why would this candidate be using multiple fonts?”

An expert in political messaging, Haenschen and Daniel Tamul, also an assistant professor in the Department of Communication, transformed the question into a captivating research project.

“What’s in a Font?: Ideological Perceptions of Typography” questions the potential impact on voters if fonts are found to have political attributes.

Haenschen and Tamul reached the following key conclusions through the study:

Individuals perceive fonts to have liberal or conservative leanings.

The more people view a font as aligned with their ideology, the more they favor it.

Fonts that fall under the serif category — ones festooned with a small line or stroke — are viewed as more conservative than fonts in the sans serif group, though differences exist within font families.

“This research is of interest to anyone who cares about political communications, and the results have clear implications for political campaign professionals,” said Haenschen. “When you’re choosing a candidate’s visual identity, you need to consider how people perceive that font.”

The findings came from two survey experiments. The first used typeface classification, such as serif or sans serif, and typeface styles (regular, bold, italic).

A total of 987 survey participants read the phrase “the quick brown fox jumped over the lazy dog” presented in each typeface style, and two typefaces representing the serif and sans serif categories: Times New Roman and Gill Sans.

The respondents then rated the typeface as liberal or conservative, and answered several demographic measures related to their political ideology, party affiliation, age, gender, and race.

During the second experiment, Haenschen and Tamul used a wider range of typefaces, including multiple typefaces within the same font family.

Participants read a phrase or a name written in one of two serifs (Jubilat or Times New Roman), one of two sans serifs (Gill Sans or Century Gothic), and one display font (Sunrise, Birds of Paradise, or Cloister Black Light).

The researchers said they chose the Jubilat font because it was used in Sen. Bernie Sanders’ 2016 presidential bid, and Century Gothic because of its close approximation to the Gotham font used by former President Barack Obama during his 2008 campaign.

Overall, results showed that typefaces, typeface classifications, and typeface styles are perceived to have different ideological leanings, and partisanship moderates ideological perception.

Haenschen emphasized that the exploratory story suggests many avenues for further research.

“This study shows that font plays a role in American political communication, conveying ideology through the anatomy of its letterforms,” said Haenschen. “Through this research, we lay the groundwork for future studies that may identify relationships between fonts and persuasive outcomes in political communication.”

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Materials provided by Virginia Tech. Original written by Andrew Adkins. Note: Content may be edited for style and length.

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The skin of Earth is home to Pac-Man-like protists

Pac-Man, the open-mouthed face of the most successful arcade game ever, is much more well-known than any of the one-celled organisms called protists, at least among people over 30. But the first study to characterize protists in soils from around the world — co-authored by Smithsonian scientists — found that the most common groups of soil protists behave exactly like Pac-Man: moving through the soil matrix, gobbling up bacteria. Their results are published in Science Advances.

“As part of a bigger project to understand all of the microbes in soil we are characterizing bacteria and fungi, but also a lesser-known, but equally important group called protists,” said Angela Oliverio, former STRI intern and lead author on the paper with professor Noah Fierer and post-doctoral fellow Manuel Delgado-Baquerizo at the University of Colorado, Boulder; staff scientist Ben Turner at the Smithsonian Tropical Research Institute in Panama; researcher Stefan Geisen at the Netherlands Institute of Ecology and professor Fernando Maestre at the Universidad Rey Juan Carlos and the Universidad de Alicante, Spain.

Protists reproduce quickly and are probably much more responsive to climate change than larger forms of life. Like the cartoon character Sheldon Plankton in Spongebob Squarepants, protists are not plants, animals or fungi. They are single-celled organisms but, unlike bacteria, they have a nucleus. They move through water using whip-like flagellae and tiny hairs called cilia. Some of the nastier protists cause sleeping sickness, malaria and red tide, but nearly all play important, if mysterious, roles in the energy- and nutrient-trading relationships that connect ecosystems.

Identifying millions of miniscule protists in soil used to be impossible, but recently-developed technology to classify protists based on their genetic code makes it possible to characterize them on a large scale. The team sequenced the 18S ribosomal RNA studied from soil samples from across six continents to better understand the ecological roles of the protists in the below-ground ecosystem.

They discovered that most of the protists are the Pac-Man type that consume other, smaller organisms. But in tropical soils, a larger number of protists were parasites, living inside other organisms. In desert soils, there were more protists capable of photosynthesizing and using sunlight directly as an energy source. The best predictor of what types of protists exist in a sample is the annual precipitation at the site. This may seem intuitive because protists depend on water to move, but it was a surprise, since soil acidity, rather than precipitation, is what usually predicts which bacteria and fungi are in soil.

“Soils are home to an astonishing diversity of organisms, the lives of which we are only beginning to understand,” said Ben Turner, STRI staff scientist and co-author of the study. “Soil protists are an understudied group, so this work provides a foundation for future research on their ecology in ecosystems worldwide.”

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Materials provided by Smithsonian Tropical Research Institute. Note: Content may be edited for style and length.

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China coronavirus: UK tracing up to 2,000 Wuhan visitors

So far tests on 14 people in the UK have shown to be negative, the chief medical officer says.

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Health24.com | What parents can do to prevent teens from driving drunk

Older teens who know that their parents disapprove of drinking are less likely to drive impaired as young adults, a new study finds.

“As kids get older, we tend to step away from them. We think: ‘They’ve got this.’ But if kids think we approve or disapprove of them drinking, that can have a powerful effect,” said lead author Dr Federico Vaca, director of the Yale Developmental Neurocognitive Driving Simulation Research Center in New Haven, Connecticut.

Binge-drinking episodes

The new study included nearly 2 800 American teens who were followed for seven years.

By grade 12, 42% said they’d had alcohol in the past month, and 25% had at least one binge-drinking episode. Binge drinking is defined as four or more drinks in two hours for women, and five or more for men.

Compared to those who did not binge-drink in grade 12, those who did were six times more likely to drive impaired two years later and more than twice as likely to drive impaired four years later.

Teens who binge-drank in grade 12 were also more likely to ride with an impaired driver, to have alcohol-related blackouts, and to indulge in extreme binges in subsequent years, according to the study. Extreme bingeing – 15 or more drinks on a single occasion – is a growing concern.

Great prevention power

However, the study also found that parents could reduce their teens’ future risk of impaired driving.

If teens in the 12th grade knew that their parents disapproved of drinking, it lowered the chances of their driving while impaired by 30% four years later, and of riding with an impaired driver by 20% one year later. It also lowered later odds of blackout by 20%.

“There is great prevention power in intentional parenting, and a strong, reliable, mutual relationship here can make all the difference in the world, including helping to identify the development of youth alcohol/drug use disorder and the need for specialised treatment services for addiction,” Vaca said in a Yale news release.

The study was published in the January issue of the journal Pediatrics.

Image credit: iStock

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