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05/01/2013

Nurturing and Chemistry

CHAPTER 33 - Parenting Counts
 
This column will be a potpourri - new planets, methylated DNA and tarnishing silver. Given my obsession with space and our universe, I must begin with NASA's Kepler mission, which just keeps giving and giving. Kepler, launched on March 6, 2009, monitors 150 thousand stars looking for a diminishing of light intensity as a planet passes between a star and us here on Earth. To date, Kepler has turned up over 2700 planetary candidates orbiting stars other than our own Sun. Over a hundred planets have been confirmed, a process which involves detection of the dimming of light at least three times and may involve observations by other space missions or ground telescopes. Naturally, it's easier to confirm planets with short years; some orbit their suns in just a few days. A planet such as our own with a 365-day year would take two years from the first observed dimming to spot three dimmings of its sun's light.
 
Previously, Kepler found a planet smaller than Earth, a major achievement. That planet, however, was not in the so-called habitable zone conducive to life as we know it. Outside the habitable zone, it's either too hot or too cold. In a press release on April 18, 2013, NASA announced the finding of two new planetary systems containing three "super-Earth-size" planets orbiting their suns in habitable zones where life could possibly exist. One of the planets is only 40 percent larger than Earth, making it the smallest planet orbiting a star in a habitable zone discovered to date. The two other planets are roughly 60 and 70 percent larger than our own planet. I'm truly impressed and imagine these planets will be the subjects of further study. I was also impressed by a comment on the TV show Sunday Morning, which recently had a short segment on Kepler. In this segment, a Kepler scientist likened the sensitivity of Kepler to observe dimming as like detecting less than the light of a flashlight on the moon! Sadly, Kepler's mission is to find planets, not to study them in detail looking for signs of life. We'll have to wait for other more powerful telescopes in the future. 
 
One possible sign of life is the presence of methane. Some time ago, there was a bit of excitement when bursts of methane were detected on a planet in our own planetary system, Mars. Methane is a potential sign of life, arising here on Earth from various sources such as microorganisms and "cow farts" (the term used in a NASA release). However, further detections of methane bursts on Mars have not been forthcoming and the Curiosity rover has failed to find any methane. Those of you who have taken chemistry will know that methane is one of the simplest organic compounds, consisting of one carbon atom and four hydrogen atoms, CH4. Take away one hydrogen and you have what we chemists call a methyl group CH3-. Add an oxygen and a hydrogen and you have methyl alcohol, CH3OH, a substance you certainly don't want to drink unless you want to die or go blind! Add a couple more hydrogens and a carbon and you get a more palatable substance, ethyl alcohol, CH3CH2OH. I may have a bit of bourbon after posting this column.
 
But I digress. Let's get back to that methyl group. After reading an article titled "Trait vs. Fate" by Dan Hurley in the May issue of Discover magazine, I realize that methyl groups play a major role in our lives. In fact, the methyl group may be a key player in the resolving the long running debate over whether it's nature or nurture that is most important in determining behavior. Let's go back to when DNA and the human genome was decoded some years ago. I remember there was optimism that, once the sequences of all those four "letters" C, G, A and T (actually bases) in the human genome were determined, all would be explained. The first shock, or at least one of them, was that the number of genes, the protein coding sections of our DNA, was much smaller than expected. Most of our DNA was thought to be "junk".   Not so; much of the "junk" has been found to play key roles in regulating what the genes produce. Without going into detail, let's get to our methyl group, which likes to hook up with elements or other groups. It is especially fond of the C in our DNA, C standing for the base cytosine. When the methyl group attaches itself to C, our DNA is said to be "methylated". 
 
Methylation of our DNA causes a change in the behavior of the gene associated with the section of our DNA where the methyl group is attached. It may shut down the production of a protein normally produced by that gene. The effect may be a simple tightening of the DNA around a molecular spool known as a histone. DNA is typically wrapped around these spools and whether or not a protein is produced can depend upon the tightness of the wrapping of the DNA on the histone spool. (There's another group, the acetyl group, that when attached to the DNA, tends to open up the tightness of the wrapping and allow the production of a given protein to proceed.)
 
If you, as I am, are confused by the chemistry, let's cut to the chase. These methyl groups can affect behavior. They may play a role in depression, PTSD and other psychiatric problems and the tendencies for some of these problems can even be passed down through generations. The Discover article concentrates on work done by Michael Meany and Moshe Szyf (don't ask me how to pronounce the name). Back in 1997 at Magill University in Montreal, Meany showed that when attentive rat mothers licked, groomed and allowed their pups to suckle frequently, the rat pups grew up with lower amounts of stress hormones than did rats who had less attentive mothers. 
 
Szyf came from a group in Israel headed by biochemist Aharon Razin. Razin's group showed that methyl groups could attach to cytosine and change the behavior of the genes. They also found that these changes could be transmitted through succeeding generations. The methyl group attachments didn't go away. Later, Szyf and Meany got together at Magill and came up with some really neat experiments that blew my mind. First, they gathered groups of rat pups who were offspring of rat mothers who were attentive and pups from rat mothers who were not attentive. When the pups grew up, the researchers looked in the hippocampus, an area of the brain involved in regulating stress response. In the rats brought up by inattentive mothers, they found the genes that regulate stress hormones were generally highly methylated. In the group brought up by attentive mothers, the same genes were rarely methylated. How you're brought up can affect the chemistry of your genes! At least if you're a rat.
 
To nail down their finding, Szyf and Meany performed another experiment. They took batches of rat pups born to attentive mothers and rats born to inattentive mothers and then switched the batches to be raised by the opposite type of mother. Sure enough, the pups raised by the good mothers grew up with low levels of methylation of the stress related genes and were calm and brave. The pups raised by the bad mothers had highly methylated genes and were skittish. Nurture wins out over nature in this case.
 
Meany and Szyf weren't finished. There's a drug called trichostatin A that can strip away methyl groups. They took a batch of rat pups raised by bad mothers and injected the drug into their brains. If I were a rat, I wouldn't be too happy having something pumped into my brain but, amazingly, those pups grew up to be well adjusted rats without those methyl groups lousing up their brains! All this work has been done in a field that has become known as epigenetics, a term you may have encountered and certainly will be seeing or hearing more frequently in the future. In the cases I've cited, the term comes from the Greek prefix epi, meaning over, outer or above. In methylation, the methyl group that affects the gene behavior is attached to, but sits outside of the DNA chain; hence the term epigenetics. 
 
Meany and Szyf published their monumental work in 2004 in the face of much skepticism that mothering could lead to epigenetic change. Naturally, the question that comes next is could this be true in humans? Szyf, Meany and others are pursuing this question. It's a lot harder to do experiments with humans, of course. One study Szyf and Meany did was to look at the brains of people who had committed suicide and compare them with brains of people who died from things other than suicide. They found excess methylation of genes in the hippocampus of suicide victims compared to the genes in those who died of other causes. They also found that, if the suicide victims were abused as children, the brains were more methylated. Clearly, the field of epigenetics is wide open. Could methylation play a role in various psychiatric disorders such as PTSD, bipolar disorder or other maladies? If so, should we start using drugs to strip out the methyl groups? If we do, would we also be stripping away methyl groups that are keeping genes in check that should be squelched? Stay tuned. 
 
I was prompted to close this column with a bit on the subject of tarnished silver when my wife dropped the spoon from a rarely used sugar bowl in our breakfast room. I hadn't realized the spoon was silver or silver plated until I saw that it was definitely tarnished. Before we were married, my wife had started to purchase items of silverware and continued to do so until we had a complete service that we would bring out for dinners on special occasions. We haven't used the silverware in years, partly due to the fact that in our advancing years our progeny thankfully have assumed the hosting of such occasions as Christmas and Thanksgiving. As I imagine with most people, we didn't use the silver on a daily basis because of the need to polish it every so often. Unlike our stainless steel utensils, silver reacts with sulfur in the air, tarnishing it with a coating of silver sulfide, which silver polish removes.
 
Bear with me. We'll get back to silver. I've mentioned previously an experience I had when working at NACA Lewis Flight Propulsion Laboratory in Cleveland some 60 years ago. I had read an article about levitation of objects in a furnace of a certain design. I had access to an induction furnace and decided to see if I could levitate a cube of aluminum metal. To my delight, I found that I could and I then decided to see what happened if I melted the aluminum. I was amazed to see that after the aluminum cube melted and, still suspended in midair, the molten metal maintained its cubic shape! What made this possible was the thin sturdy film of aluminum oxide that forms on aluminum. Aluminum metal is quite reactive and it's this oxide film that allows you to use your aluminum cookware. 
 
Back to silver. In the March 29, 2013 issue of Science, I saw a brief news item about preserving ancient silver artifacts in museums. To keep the silver artifacts bright and shiny, polishing on a frequent basis can wear down the artifact since each polishing gets rid of some of the silver. Preservative coatings apparently only last a couple of decades and scientists from the University of Maryland have proposed using a technique known as atomic layer deposition to lay down very thin films of aluminum oxide to serve as a protective coating. The technique is capable of filling every nook and cranny of an artifact and will be tested on an ornate 15th century Spanish cross. If this approach proves practical, I'm thinking that all that silverware that never gets used might be used routinely if an aluminum oxide coating were applied by the manufacturer. 
 
If you're a mom or a dad, pay good attention to your kids!
 
Next column, hopefully, will be posted on or about June 1.
 
Allen F. Bortrum

 



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-05/01/2013-      
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Dr. Bortrum

05/01/2013

Nurturing and Chemistry

CHAPTER 33 - Parenting Counts
 
This column will be a potpourri - new planets, methylated DNA and tarnishing silver. Given my obsession with space and our universe, I must begin with NASA's Kepler mission, which just keeps giving and giving. Kepler, launched on March 6, 2009, monitors 150 thousand stars looking for a diminishing of light intensity as a planet passes between a star and us here on Earth. To date, Kepler has turned up over 2700 planetary candidates orbiting stars other than our own Sun. Over a hundred planets have been confirmed, a process which involves detection of the dimming of light at least three times and may involve observations by other space missions or ground telescopes. Naturally, it's easier to confirm planets with short years; some orbit their suns in just a few days. A planet such as our own with a 365-day year would take two years from the first observed dimming to spot three dimmings of its sun's light.
 
Previously, Kepler found a planet smaller than Earth, a major achievement. That planet, however, was not in the so-called habitable zone conducive to life as we know it. Outside the habitable zone, it's either too hot or too cold. In a press release on April 18, 2013, NASA announced the finding of two new planetary systems containing three "super-Earth-size" planets orbiting their suns in habitable zones where life could possibly exist. One of the planets is only 40 percent larger than Earth, making it the smallest planet orbiting a star in a habitable zone discovered to date. The two other planets are roughly 60 and 70 percent larger than our own planet. I'm truly impressed and imagine these planets will be the subjects of further study. I was also impressed by a comment on the TV show Sunday Morning, which recently had a short segment on Kepler. In this segment, a Kepler scientist likened the sensitivity of Kepler to observe dimming as like detecting less than the light of a flashlight on the moon! Sadly, Kepler's mission is to find planets, not to study them in detail looking for signs of life. We'll have to wait for other more powerful telescopes in the future. 
 
One possible sign of life is the presence of methane. Some time ago, there was a bit of excitement when bursts of methane were detected on a planet in our own planetary system, Mars. Methane is a potential sign of life, arising here on Earth from various sources such as microorganisms and "cow farts" (the term used in a NASA release). However, further detections of methane bursts on Mars have not been forthcoming and the Curiosity rover has failed to find any methane. Those of you who have taken chemistry will know that methane is one of the simplest organic compounds, consisting of one carbon atom and four hydrogen atoms, CH4. Take away one hydrogen and you have what we chemists call a methyl group CH3-. Add an oxygen and a hydrogen and you have methyl alcohol, CH3OH, a substance you certainly don't want to drink unless you want to die or go blind! Add a couple more hydrogens and a carbon and you get a more palatable substance, ethyl alcohol, CH3CH2OH. I may have a bit of bourbon after posting this column.
 
But I digress. Let's get back to that methyl group. After reading an article titled "Trait vs. Fate" by Dan Hurley in the May issue of Discover magazine, I realize that methyl groups play a major role in our lives. In fact, the methyl group may be a key player in the resolving the long running debate over whether it's nature or nurture that is most important in determining behavior. Let's go back to when DNA and the human genome was decoded some years ago. I remember there was optimism that, once the sequences of all those four "letters" C, G, A and T (actually bases) in the human genome were determined, all would be explained. The first shock, or at least one of them, was that the number of genes, the protein coding sections of our DNA, was much smaller than expected. Most of our DNA was thought to be "junk".   Not so; much of the "junk" has been found to play key roles in regulating what the genes produce. Without going into detail, let's get to our methyl group, which likes to hook up with elements or other groups. It is especially fond of the C in our DNA, C standing for the base cytosine. When the methyl group attaches itself to C, our DNA is said to be "methylated". 
 
Methylation of our DNA causes a change in the behavior of the gene associated with the section of our DNA where the methyl group is attached. It may shut down the production of a protein normally produced by that gene. The effect may be a simple tightening of the DNA around a molecular spool known as a histone. DNA is typically wrapped around these spools and whether or not a protein is produced can depend upon the tightness of the wrapping of the DNA on the histone spool. (There's another group, the acetyl group, that when attached to the DNA, tends to open up the tightness of the wrapping and allow the production of a given protein to proceed.)
 
If you, as I am, are confused by the chemistry, let's cut to the chase. These methyl groups can affect behavior. They may play a role in depression, PTSD and other psychiatric problems and the tendencies for some of these problems can even be passed down through generations. The Discover article concentrates on work done by Michael Meany and Moshe Szyf (don't ask me how to pronounce the name). Back in 1997 at Magill University in Montreal, Meany showed that when attentive rat mothers licked, groomed and allowed their pups to suckle frequently, the rat pups grew up with lower amounts of stress hormones than did rats who had less attentive mothers. 
 
Szyf came from a group in Israel headed by biochemist Aharon Razin. Razin's group showed that methyl groups could attach to cytosine and change the behavior of the genes. They also found that these changes could be transmitted through succeeding generations. The methyl group attachments didn't go away. Later, Szyf and Meany got together at Magill and came up with some really neat experiments that blew my mind. First, they gathered groups of rat pups who were offspring of rat mothers who were attentive and pups from rat mothers who were not attentive. When the pups grew up, the researchers looked in the hippocampus, an area of the brain involved in regulating stress response. In the rats brought up by inattentive mothers, they found the genes that regulate stress hormones were generally highly methylated. In the group brought up by attentive mothers, the same genes were rarely methylated. How you're brought up can affect the chemistry of your genes! At least if you're a rat.
 
To nail down their finding, Szyf and Meany performed another experiment. They took batches of rat pups born to attentive mothers and rats born to inattentive mothers and then switched the batches to be raised by the opposite type of mother. Sure enough, the pups raised by the good mothers grew up with low levels of methylation of the stress related genes and were calm and brave. The pups raised by the bad mothers had highly methylated genes and were skittish. Nurture wins out over nature in this case.
 
Meany and Szyf weren't finished. There's a drug called trichostatin A that can strip away methyl groups. They took a batch of rat pups raised by bad mothers and injected the drug into their brains. If I were a rat, I wouldn't be too happy having something pumped into my brain but, amazingly, those pups grew up to be well adjusted rats without those methyl groups lousing up their brains! All this work has been done in a field that has become known as epigenetics, a term you may have encountered and certainly will be seeing or hearing more frequently in the future. In the cases I've cited, the term comes from the Greek prefix epi, meaning over, outer or above. In methylation, the methyl group that affects the gene behavior is attached to, but sits outside of the DNA chain; hence the term epigenetics. 
 
Meany and Szyf published their monumental work in 2004 in the face of much skepticism that mothering could lead to epigenetic change. Naturally, the question that comes next is could this be true in humans? Szyf, Meany and others are pursuing this question. It's a lot harder to do experiments with humans, of course. One study Szyf and Meany did was to look at the brains of people who had committed suicide and compare them with brains of people who died from things other than suicide. They found excess methylation of genes in the hippocampus of suicide victims compared to the genes in those who died of other causes. They also found that, if the suicide victims were abused as children, the brains were more methylated. Clearly, the field of epigenetics is wide open. Could methylation play a role in various psychiatric disorders such as PTSD, bipolar disorder or other maladies? If so, should we start using drugs to strip out the methyl groups? If we do, would we also be stripping away methyl groups that are keeping genes in check that should be squelched? Stay tuned. 
 
I was prompted to close this column with a bit on the subject of tarnished silver when my wife dropped the spoon from a rarely used sugar bowl in our breakfast room. I hadn't realized the spoon was silver or silver plated until I saw that it was definitely tarnished. Before we were married, my wife had started to purchase items of silverware and continued to do so until we had a complete service that we would bring out for dinners on special occasions. We haven't used the silverware in years, partly due to the fact that in our advancing years our progeny thankfully have assumed the hosting of such occasions as Christmas and Thanksgiving. As I imagine with most people, we didn't use the silver on a daily basis because of the need to polish it every so often. Unlike our stainless steel utensils, silver reacts with sulfur in the air, tarnishing it with a coating of silver sulfide, which silver polish removes.
 
Bear with me. We'll get back to silver. I've mentioned previously an experience I had when working at NACA Lewis Flight Propulsion Laboratory in Cleveland some 60 years ago. I had read an article about levitation of objects in a furnace of a certain design. I had access to an induction furnace and decided to see if I could levitate a cube of aluminum metal. To my delight, I found that I could and I then decided to see what happened if I melted the aluminum. I was amazed to see that after the aluminum cube melted and, still suspended in midair, the molten metal maintained its cubic shape! What made this possible was the thin sturdy film of aluminum oxide that forms on aluminum. Aluminum metal is quite reactive and it's this oxide film that allows you to use your aluminum cookware. 
 
Back to silver. In the March 29, 2013 issue of Science, I saw a brief news item about preserving ancient silver artifacts in museums. To keep the silver artifacts bright and shiny, polishing on a frequent basis can wear down the artifact since each polishing gets rid of some of the silver. Preservative coatings apparently only last a couple of decades and scientists from the University of Maryland have proposed using a technique known as atomic layer deposition to lay down very thin films of aluminum oxide to serve as a protective coating. The technique is capable of filling every nook and cranny of an artifact and will be tested on an ornate 15th century Spanish cross. If this approach proves practical, I'm thinking that all that silverware that never gets used might be used routinely if an aluminum oxide coating were applied by the manufacturer. 
 
If you're a mom or a dad, pay good attention to your kids!
 
Next column, hopefully, will be posted on or about June 1.
 
Allen F. Bortrum