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February 11th, 2016:

Neanderthal DNA may account for nicotine addiction and depression

Matching modern genetic profiles against genes known to have been inherited from Neanderthals has shown links to a wide range of current disorders

Modern European and Asian people may owe more than skin or hair colour to Neanderthal ancestry. Interbreeding 50,000 years ago between two species of human may also have bequeathed a sunburn hazard called keratosis, addiction to nicotine, and a greater risk of depression.

That the forebears of modern Homo sapiens and the long-extinct Neanderthals lived side by side is well known: that they interbred, and that up to 4% of modern human DNA is inherited from the first Europeans, was confirmed only in 2010.

US researchers examined a database of 28,000 patients whose biological samples had been linked to versions of their medical records. Identities remained anonymous but the researchers could see how inheritance linked to medical history.

Then, they report in the journal Science, they matched the modern human database against a map of those groups of genes known to have been inherited from the big-boned, heavy-browed, red-haired humans whose ancestors had moved out of Africa long before Homo sapiens, and colonised Ice Age Europe.

“Our main finding is that Neanderthal DNA does influence clinical traits in modern humans,” said John Capra, an evolutionary geneticist at Vanderbilt University in Nashville, Tennessee. “We discovered associations between Neanderthal DNA and a wide range of traits, including immunological, dermatological, neurological, psychiatric and reproductive diseases.”

Sub-Saharan African peoples do not inherit Neanderthal DNA. The assumption is that the Neanderthals left Africa first, had time to adapt to a colder, darker and more difficult world, evolved paler skin colour to take advantage of less certain sunlight, and developed other traits that might have helped them survive changing conditions.

Early modern humans – more gracile, and perhaps quicker to adapt and take advantage of their environment – then migrated north from Africa to outpace and outlive the first Europeans. But, during the thousands of years the two species coexisted, they also interbred.

And these encounters passed on traits that might have been of some evolutionary advantage in an Ice Age world. But in changing conditions, the same lengths of inherited DNA contained greater health liabilities as well.

One of these, the researchers think, was a Neanderthal gene variant that increases blood-clotting. This would have sealed wounds more quickly, and prevented infection more easily. But in a modern western society, hyper-coagulation brings other problems, including greater risk for stroke, pulmonary embolism and pregnancy complications.

One length of Neanderthal DNA is now linked to increased risk of nicotine addiction, and several variants influence the risk of mood disorders, including depression. As tobacco was introduced into widespread use in Europe only 400 years ago, the researchers were surprised at the number of Neanderthal genetic variants now associated with modern psychiatric and neurological disorders.

“The brain is incredibly complex, so it is reasonable to expect that introducing changes from a different evolutionary path might have negative consequences,” said Corinne Simonti, a Vanderbilt doctoral student and the study’s first author.

E-cigarettes ‘as dangerous for unborn babies as regular tobacco’

Research finds that exposure to volatile chemicals from the devices disrupts the activity of thousands of genes in the developing frontal cortex

Pregnant women who smoke may harm their babies’ brain development if they turn to e-cigarettes to satisfy their nicotine craving, scientists have warned.

New research suggests that e-cigarette vapour may be as damaging as tobacco smoke to the nervous systems of the foetus or newborn infant.

The early findings, based on studies of mice, show that exposure to volatile chemicals from the devices disrupts the activity of thousands of genes in the developing frontal cortex, the brain region responsible for higher mental functions.

Analysis of the altered gene activity patterns indicated that they could lead to reductions in learning, memory and co-ordination, and increases in hyperactive behaviour.

These are just the sort of neurological effects seen in children whose mothers smoked during pregnancy and who are known to be at risk of attention deficit hyperactivity disorder (ADHD) and learning difficulties.

A further study, still on-going, has shown that older mice exposed to e-cigarettes in the womb or just after birth do indeed appear to be hyperactive, running around at a faster rate than normal.

Lead scientist Professor Judith Zelikoff, from New York University in the US, said: “This is ground-breaking research. What it shows is that there is certainly some concern over the safety of e-cigarettes, particularly in relation to pregnant women or young infants.

“There are potential dangers revealed by these studies indicating a possible impact to the unborn child that may be seen at birth but may occur later in the life of the child.

“Women may be turning to these products as an alternative because they think they’re safe. Well, they’re not.”

Colleague Dana Lauterstein, a PhD student at the university who did much of the work, added: “Most people view e-cigarettes as a safe way to smoke. For women who are pregnant, this could be dangerous. They could unwittingly be endangering their child.”

Prof Zelikoff’s team started out expecting to see effects from nicotine, which previous research has suggested may have an impact on brain development.

The whole point of e-cigarettes is that they deliver a dose of nicotine minus the highly damaging cocktail of other chemicals found in tobacco.

For this reason they have been touted as a “healthier” alternative for smokers who lack the will to quit, or a cessation aid that can help to wean them off tobacco.

But recent studies have challenged the view that apart from its addictive properties, nicotine on its own is harmless.

And the new research shows that other e-cigarette chemicals besides nicotine have an even bigger effect on developing nervous systems than the tobacco compound.

In the gene activity study, mice exposed to e-cigarette vapour with its nicotine removed experienced the largest number of changes, with some genes being boosted and others suppressed. Females were more affected than males.

Prof Zelikoff said: “That was really surprising. We were shocked. But what people don’t realise is that even without nicotine there are many things that are given off when you heat up and vaporise these products.”

Two major components in e-cigarettes are propylene glycol and vegetable glycerin. In addition, various flavourings may be added.

The findings were presented at the start of the American Association for the Advancement of Science (AAAS) annual conference in Washington DC, the world’s largest general science meeting.

In the first study, 30 to 40 normal pregnant mice were exposed to e-cigarette vapour from the popular “Blu” brand, with or without nicotine, or allowed to breathe ordinary air. Dose levels were “relatively low”, said the scientists.

The exposure lasted the full length of the mothers’ pregnancies, about three weeks. Four days after birth, their offspring underwent the same exposures for another three weeks.

Tissue samples from the animals’ brains were then tested for gene activity. Intelligent software was used to predict the likely effects of the patterns seen, based on the results of previous genetic research.

The second study involved around 60 three-month-old mice. Activity levels were found to be significantly higher in male and female mice that had been exposed to e-cigarette vapour, with or without nicotine. This time refillable “tank” e-cigarettes were used.

E-cigarette exposure was also associated with greater “vertical time” – how much time the mice spent rearing on two legs, which is linked to exploratory behaviour and curiosity.

The implications of this are not certain but it could indicate a propensity for risk taking, the scientists believe.

Prof Zelikoff challenged the idea that e-cigarettes played a valuable role in helping people quit tobacco.

“Many people who use e-cigarettes are dual users,” she said. “They enjoy e-cigarettes and they smoke. And e-cigarettes can be a gateway – there are concerns that adolescents are starting with e-cigarettes and going onto real cigarettes.

“It’s not straightforward. There isn’t hard evidence that e-cigarettes are working in that regard.”

Professor Adam Balen, chairman of the British Fertility Society, said: “Whilst e-cigarettes may help some people to stop smoking real cigarettes, one cannot escape the reality that various chemicals are still being inhaled that have potentially harmful effects both to health, fertility and also the non-consenting participant, that is the baby.

“It may therefore be wrong to switch during pregnancy and best to avoid all kinds of smoking.”

In the UK, a hi-tech e-cigarette called Evoke – which can communicate with smartphones – has recently been licensed as a medicine by the Medicines and Healthcare products Regulatory Agency (MHRA).

A spokesman for the agency said: “It is a product of acceptable quality and can be an effective aid to smoking cessation.

“We hope to see more e-cigarettes and next generation nicotine delivery product medicines licensing applications in the future.”

Other research by the same US team has suggested that exposure to e-cigarettes may have a harmful effect on male fertility.

In another mouse study, three to five-week-old male offspring whose mothers had been exposed to e-cigarette vapour were found to have lower concentrations of sperm. Their sperm was also significantly less active than non-exposed mice.

Talking with … An anti-tobacco crusader

Name: Stanton Glantz

Age: 69

City: San Francisco

Position: Professor of medicine at UCSF, director of Center for Tobacco Control, Research and Education

Stanton Glantz

J.: It’s been a few years since the fight against big tobacco was a big news item. Where does that fight stand now?

Stanton Glantz: We haven’t solved the problem but we’ve made dramatic progress. Here in California, for example, we’ve dramatically cut the smoking rate down to 11 or 12 percent, and most smokers are relatively light smokers. But there are still millions of smokers. And the tobacco companies have become more active in the state Legislature. California has the 33rd lowest cigarette tax rate in the country. Jerry Brown is the first governor in decades to take tobacco campaign money.

I was surprised to find that you’re not an M.D. Your education was in engineering, including your undergrad, master’s and Ph.D. studies. How did you first get into anti-tobacco work?

I started out as a rocket scientist. I worked in several different areas at NASA, but I spent the largest amount of my time working in the mission planning and analysis divisions where we actually design the missions. I got interested in a project to use the same kind of methods that are used to control spacecraft to control anesthesia, which turns out to be a harder problem. That led to a dissertation on how the heart muscle works. Then I spent the first chunk of my career as an academic doing bioengineering, applying engineering concepts to how the heart and cardiovascular system work. And then the tobacco stuff was sort of a hobby that I got interested in in the late ’70s. It’s become a big part of my life, but I still do cardiovascular research and publish in those journals.

One of your projects is called SmokeFreeMovies, which has a website where people can see which current movies include smoking. What’s the goal of that campaign and what kind of success have you had with it?

Smoking in the movies is the major reason kids start smoking. I realized that we weren’t going to solve this talking with studios in the backrooms because tobacco has been putting money into Hollywood going back a long time. So we started this public campaign to get smoking out of movies. The six major studios now have policies discouraging smoking in their youth-rated movies. The amount of smoking in movies in 2015 was about half what it once was. The big goal for the next year is to get rid of the remaining half.

There’s a lot of new research on e-cigarettes. What is their impact and what do people need to know?

It’s true that heating up a [nicotine] solution does not create as many cancer-causing chemicals — but most people who are using e-cigarettes are not abandoning regular cigarettes, but using the two together. The odds of quitting smoking are 28 percent lower in smokers who use e-cigarettes compared to smokers who don’t. More kids are starting nicotine addictions through e-cigarettes, and those who do are more likely to go on to smoke regular cigarettes. San Francisco has integrated e-cigarettes into its indoor clean air law, but Alameda County just refused to.

The tobacco industry has twice sued the University of California over your work. What can you tell me about that?

On May 12, 1994, I got a box of purloined industry documents sent to me anonymously. The tobacco companies sued the university, trying to prevent us from releasing them, and we beat them. The second time, the tobacco industry claimed indoor smoking laws would destroy restaurant revenue, but our research found that to be false. So they sued the university on that, and it was dismissed because they didn’t have a case. But the tobacco companies are bullies with infinite money so they appealed it all the way up the Supreme Court. They lost.

Do Jewish ethics play a role in your work?

They play a big role. Historically, Jews have been on the edge, and we’re willing to take some risks that some others might not. Underlying attitudes built into Jewish culture have certainly been an element in why I am who I am and why I do what I do. My wife and I are members of Congregation Beth Sholom in San Francisco, and my wife is very active. We do Shabbos every week and always have, but I’m more into the ethical and prophetic part of the Jewish tradition, rather than ritualistic stuff.

E-Cigarettes’ Effect On The Immune System Could Make Them No Better Than Regular Cigarettes

Electronic cigarettes, or e-cigs, have been marketed in the United States since 2007. Many people believe vaping is not very harmful, perhaps because of the fanciful flavors — everything from cotton candy to tangerine. New research from UNC School of Medicine suggests the opposite may be true with evidence that cinnamon-flavored e-liquids not only harm epithelial cells, but also change immune responses in our airways.

In previous work, Dr. Ilona Jaspers, a professor and director of the curriculum in toxicology, demonstrated how smoking regular cigarettes impaired the immune responses of mucosal cells within the respiratory system. She wondered if vaping did similar damage.

For her current study, Jaspers and her colleagues obtained tissue samples of the epithelial layer inside the nasal cavities of smokers, non-smokers, and users of e-cigarettes. Examining the samples, the team analyzed expression of nearly 600 genes involved in immunity. The researchers also obtained nasal fluid, urine, and blood samples from the participants to study inflammation, immunity, and possible changes occurring as a result of tobacco and nicotine exposure.

“Our data indicate that cinnamaldehyde-containing e-liquids have a significant negative effect on epithelial cell physiology and barrier function,” Jaspers wrote in her presentation to the American Association for the Advancement of Science, while also noting the cinnamon-flavored liquids, when inhaled, compromise respiratory immune cell function.

Smoking Vs. Vaping

While smoking cigarettes caused suppression of several key immune genes in the nasal mucosa, the data showed e-cig vapers were even worse. Along with suppressing the same key immune genes in the nasal mucosa, e-cigarette vapers also dampened the positive actions of additional immune genes.

This possibly broad effect on the respiratory immune response system, Jaspers theorized, might have something to do with the flavoring. Though the Food and Drug Administration rates the liquid flavorings as “safe” for oral consumption, they’ve never been tested for inhalation.

In separate experiments using cell cultures, Jaspers’ lab examined the effects of cinnamaldehyde — the chemical flavoring that makes an e-cigarette taste like cinnamon. Cinnamaldehyde e-liquids had a “significant” negative effect on epithelial cell physiology, the results showed. The chemicals hindered key immune cells, including macrophages, natural killer cells, and neutrophils.

This compromised immune function could begin a whole cascade of cellular mechanisms that ultimately lead to impaired immune responses in the lung, Jaspers says.

Going forward, she and her colleagues will experiment to understand the health effects of long-term exposure to e-cigarettes, especially cinnamon-flavored e-cigs. Because they are increasingly popular among teens and young adults — because so many people don’t believe they are harmful — the question of potential needs to be answered.

Secondhand smoke exposure at home among one billion children in 21 countries

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