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Frogger, More Than just a Game December 12, 2010

Posted by zach in Biology, Chemistry, Ecology, Environment/Conservation, Health.
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As a child you learned that a frog isn’t born as a litGraphic depicting life stages of a tadpole to a frogtle frog, but rather its life begins as an egg and develops into a frog through metamorphosis. This poses a lot of interesting questions for molecular biology because appendages have to grow at the same time the tadpoles tail is lost. The frog is an ideal model organism for how morphological changes can take place, since frogs are so easily kept in captivity it’s easy to manipulate their environment. When you are able to change their environment it makes it easier to identify what hormones, enzymes, or other environmental cues influence how the tadpole develops into a frog.

One hormone that has been shown to affect the metamorphosis of tadpoles is thyroid hormone (TH). In the presence of dilute concentrations of thyroid hormone the frog’s metamorphosis is accelerated.   The converse is also true, when TH is blocked by compounds such as goitrogens, tadpoles will not develop into frogs but, stay in the tadpole life stage.  We know that TH acts through nuclear receptors to activate transcription or, the process of DNA going to mRNA then translated into proteins.  With many advances taking place in the field of biochemistry my question is how is the structure of the chromatin affected through metamorphosis?  What chemical present in local ponds affect the structure of the chromatin?  There are many different mechanisms in which the structure of the chromatin can be altered.

 

Two of the most common ways the structure of the chromatin is altered is by methylation, which is adding a methyl group to a cytosine nucleotide, or acetylation, which is the process of adding an acetyl group on to the lysine residue on histones. Both methylation and acetylation can function to change gene expression. Methylation causes a steric hindrance for the transcriptional machinery and acetylation alters how much the gene is exposed to transcriptional machinery.  Both methylation and acetylation takes place through enzymes that cause a change in how the transcriptional machinery operates.  The enzymes can be influenced by a variety of different means, for example acetylation of histone H4 lysine acetylation can be blocked by Nickel compounds.

The question that I want t0 ask is what effects are on the epigenome, when frogs are exposed to pollutants at different life stages? When tadpoles are exposed to high levels of Ni2+ compounds they all die. Is the death of the tadpoles a result of an absence of H4 lysine acetylation or through a different molecular mechanism?  Since epigenetic mechanisms are critical to regulating gene expression it is plausible that the epigenome is tightly correlated with tadpole metamorphosis. Since the habitats of amphibians are becoming more and more polluted, it is urgent to discover the mechanisms in which their metamorphosis acts though in order to reduce a certain group of pollutants.

Decreasing Ageing affect on Memory October 15, 2010

Posted by zach in Health, Medicine, Neuroscience, Physiology.
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Have you recently misplaced your car keys and spent hours trying to find them? A resent article from Science Daily explains how misplacing your keys may be a thing of the past.  A promising new drug candidate is currently being developed at the  University of Edinburgh to reverse age-related memory loss.  The researchers have developed a compound that has improved cognitive function and memory in aging mice. This compound works by blocking an enzyme known as 11beta-HSD1.  As we age our body changes, with these changes comes changes in the concentration of the enzymes in our body.  The cause of these enzymatic changes is not fully known but it can be linked to physiological effects such as stress.

The aging enzyme

11beta-HSD1 is an enzyme that is found in the brain which can produce stress hormones such as the glucocorticoids.  When there are high levels of glucocorticoids in the brain negatively affect memory.  Therefore, if we can find a way to block 11beta-HSD1 we could increase our memory by decreasing the negative pressure on memory. The problem with blocking 11beta-HSD1 is that until now it hasn’t been possible to find a molecule that has a high specificity for blocking only 11beta-HSD1.  After ingesting a synthetic compound that blocks 11beta-HSD1,  mice show a dramatic increase in memory after only ten days.  The increase in memory was quantified by the time it took mice to complete a Y maze.

A burgeoning field of research

The research in the biomedical world is very concentrated on developing medicines that will reduce or even try to eliminate the effects of aging.  In the past I have blogged about how targets of rapamycin act as a master regulator for protein synthesis.  If we could find a drug to regulate that regulated TOR we could in turn regulate aspects of how our body ages.  Maybe some day we will have a set of anti-aging drugs that will allow us to combat all the negative effects that come with growing old.  If researchers can keep developing synthetic compounds to stop memory loss there may be a day when you will never forget where you misplaced your keys.

Epigenetics May 3, 2010

Posted by zach in Biology, Genetics, Health, Medicine.
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Is it possible to find a way to fight a broad spectrum of human disease with a single break through in the in the biomedical world?  The emerging field of epigenetics is trying to lead the way in fighting a variety of human diseases, such as cancer, heart disease, and even neurological disorders.  The field of epigenetics was discovered at the conclusion of the human genome project.  When it was found that humans and chimpanzees genomes only differed by two percent, researchers knew something more than simply sequence differences had to be taking place.   Epigenetics was born, currently researchers are looking into all the mechanisms by which gene expression can be altered due to modifications of the DNA by using methyl groups and acetylation.

Epigenetic has had two major break throughs by showing how modification of the histones and methylation patterns can affect the organisms. The first study was done on pregnant agouti mice.  When there is a cross between two agouti mice the offspring usually comes out as an agouti, but scientist wondered if they changed the mother’s diet by adding meth donors, which could change the offspring phenotype by an epigenetic alteration. When the female agouti mouse was fed a high methyl donor diet the offspring showed a normal phenotype.  This means that there was some alteration at the agouti gene that changed the offspring to silence the agouti phenotype.

The other example of epigenetics in action is studies on monozygous twins (MZ).  Monozygous twins share the same DNA because they come from a single zygote, that divided early in development.  At a young age MZ are very epigenetically similar, but as they age their epigenetic patterns begin to diverge. This divergence is highly dependant on their lifestyle. Epigenetic patterns seem to change more when the two MZ twins experience very different environments in their lifestyles.  This shows that your environment can greatly influence epigenetics which can change your disposition towards disease.

“A Ghost in your genes” is a four-part documentary that explores many aspects of epigenetics and all the possibilities that can come from it.  I really recommend taking the time to watch it.   Give it a chance…you will not be let down.

From this clip you can visually see how HDAC’s function and what is being done to  prevent disease by blocking HDAC.

Epigenetics and HDAC are thought to play a key role in the development of cancer.  The National Cancer Institute agrees and pledged $8.5 million to Oregon State University to explore how diet, epigenetics, and cancer prevention can all be related.  The grant is going towards placebo-controlled human interventions trials on colon and prostate cancer.  In the future, researchers are hoping that there research on HDAC can be generalized to fight a wide range of degenerative disorders.

Will fruits and vegetables really prevent disease? April 28, 2010

Posted by zach in Genetics, Health, Medicine, Nutrition.
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Has you mother ever told you,” You are what you eat?”

With new discoveries being made daily, there is emerging research showing the interaction between environmental and dietary influences in the development of diseases such as cancer.

A new study published in the  Journal of the National Cancer Institute shows there is a weak relationship between high fruit and vegetable intake and your overall cancer risk.  During the 1990’s it was widely thought that fruits and vegetables could prevent cancer and other diseases.  To date there is a lack of studies that could conclusively prove the claim about fruits and vegetables preventing cancer on a large-scale.  But just because they can’t prove it on a large-scale isn’t to say that you should stop eating your fruits and vegetables and go on an all fast food diet.

On a smaller scale it has been found that a substance found in vegetables can combat cancer epigenetically.

Epigenetics is the study of how gene expression can be altered without changing the underlying DNA sequence, this can be done with methyl and acetyl groups. Enzymes have been found that can effect how the chromatin is condensed. When the chromatin is in an extremely condensed state transcription is limited because the polymerases struggle to attach to the DNA template.

Histones acetyltransferaes (HATs) and histone deacetylases (HDACs) are used to add and remove an acetyl groups, these acetyl groups regulate the biochemical structure of the DNA that regulates gene expression. Three key dietary components that have been shown to affect HDAC and HAT activity  1) butyrate, which is formed by fermentation of dietary fiber in the colon, 2) diallyl disulfide is found in garlic and allium (onion family) vegetables, and 3) sulforaphane, which is found in coniferous vegetables.  All three of these substances have been shown to prevent cancer in clinical and preclinical trails by inhibiting HDAC enzymes.  Even though fruits and vegetable have yet been linked to preventing cancer on a large-scale, certain substances found in vegetables have been found to prevent cancer. Maybe it is not enough just to eat the fruits and vegetables, researchers may have to isolate these cancer fighting compounds in order to use all of natures cancer fighting power.  Even though a strong positive correlation between cancer and fruits and vegetables is yet to be found, you may want to continue to eat healthy.  From researching how diet can affect epigenetics there is a clear relationship between cancer, epigenetics, fruits, and vegetables.  Researchers are just going to have to continue to look for ways to harness some of the anticancer properties of both fruits and vegetables.

Figure 1

Visual Math April 26, 2010

Posted by zach in Math, Science & Culture.
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Look at the mountains,  it may look as if it would be impossible to use a mathematical model to show the relationships between all the peaks and valleys. In the 1970’s the mathematician Benoit Mandelbrot discovered a formula that would allow a model to be made for natural objects such as mountains and branching structures such as limbs off a tree.  Fractals use geometric shapes that can continually be split into smaller fragments.    With an infinite number of points both real and imaginary art can be made using math.  Lets look at all the cool aspects of visual math fractals opened up.

Fractal showing the surface of the mountains.

Many many iterations

This first image is of a fractal with only five iterations. In the second image is the number of iterations when it is increased to 75, giving the image a much greater level of complexity.

The image below explores the edges around a Mandelbrot set.

Now lets explore how fractals can been shown in plants.

The branching structures of the California Oak tree and the smaller sprouts keep coming off the  Romanesco Broccoli.  The fractal concept is displayed in the broccoli when one closely examines how the whole is made up of multiple, smaller, repeating  parts.

Patterns that resemble fractals are not limited to the biological world.

Fractals can also be seen in architecture, this is most apparent in European Gothic Cathedrals.  The image below has a central spire with multiple other spires, repeatedly surrounding the central one, in varying sizes.

Snowflakes

Kock snowflake starts with an equilateral triangle, each iteration replaces the middle thrid of the line segment, with a part of line segments that form an equilateral bump.

Sierpinski triangle

A Shot of Worm April 14, 2010

Posted by zach in Biology, Genetics.
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Have you ever seen a bottle of the Mexican liquor Mescal with a  caterpillar lying at the bottom and wondered why a worm is at the bottom of a bottle of alcohol?  A group of researchers at the Biodiversity Institute of Ontario had the same idea…but took it to the next level.

Did someone slip something into my drink?

The researchers looked to see if any DNA from the worm could have leaked into the alcohol.  To the researchers surprise the bottle of alcohol contained sections of nuclear DNA from the caterpillar.  When drinking Mescal with a worm at the bottom you may not be eating or drinking the worm but, you are still consuming some of the worms DNA.  Just something to think about the next time before you order a drink with a caterpillar lying at the bottom.

The worm in the bottom of a bottle of Mescal

Ethanol which is the active ingredient in an alcoholic beverage also has wide implications in genetic research.   Ethanol is commonly used as a solvent to store both samples of DNA and RNA because the samples can be frozen at extremely low temperatures and ethanol limits the formation of ice crystals which can denature the strands of DNA. From this it is not extremely surprising that the DNA from the worm is stable in liquor, which contains forty percent ethanol. It is still amazing that the DNA leaked out from the caterpillars cell’s nucleus and stayed relatively intact.

Does this taste funny to you?

The researchers took a sample of Mescal then removed all the liquid ethanol by evaporation to extract only the DNA.  Next they ran polymerase chain reactions to see if first the sample contained any DNA from the caterpillar.  This analysis found that the Mescal did contain sections of DNA that could be traced back to the worm. This sparked the researchers to see, if by using pure ethanol solvent and a sample free of any extraneous DNA, if they could extract a full genome from a sample. To the researchers surprise when they used this protocol they had success that was near perfect.  This shows that it is possible to extract DNA from a sample by less evasive techniques.  This opens up possibilities for DNA extraction where there is either too little of a sample for traditional extraction procedures or when the sample cannot be destroyed (chopped up and lysed).   With these techniques geneticist can extract DNA from samples that was not possible prior to this technique.

One more implication brought to light by this research may concern contamination. Commonly when sample are collected in the field they are placed in a jar full of ethanol to be preserved until they reach the laboratory.  If the samples are going to require genetic testing a greater level of care is now going to have to be taken to prevent contamination.

The full study is located at Bio Techniques

The Fountain of Youth April 7, 2010

Posted by zach in Biology, Genetics, Physiology.
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Sestrin molecule

Scientists at University of California, San Diego School of Medicine, are currently looking at the protein sestrin, to see how it affects signaling pathways which  affect aging.  Sestrin is highly conserved across many different species, ranging from mammals to Drosophila melanogaster…better known as the fruit fly.  Being in a wide range of organisms makes sestrin a very important candidate for research on aging.  Often study findings in fruit flies can be can be generalized to humans.

Sestrin, stress, and aging

Sestrin is regulated by stress levels in the cell, when a cell begins to experience stress, sestrin production is increased. Scientist have know about the increase of sestrin during stress for a while, but couldn’t explain the function of the greater concentration of sestrin in the cell until recently.  From looking at Drosophila it was found that sestrin functions as an activator of AMP-dependent protein kinase (AMPK) and inhibitors of Target of Rapamycin (TOR). From looking at model organisms such as C. elegans and Drosophila it was found that the main role of the AMPK and TOR signaling pathways is to control aging and metabolism.  The AMPK pathway is extremely complex; its simplified function is to act as a master regulator of cellular metabolism.  While TOR is responsible for maintaining the balance between protein synthesis and degradation based off of nutritional quantity and quality.  It is currently thought that calorie restricted diets may control the TOR pathway to combat the effects of aging.

complex cellular pathways involved in aging

What does sestrin do?

To look at the function of sestrin scientist made a knockout Drosophila or a fly who was not expressing the genes for sestrin.  In Drosophila sestrin is located on a single gene.  When the sestrin gene was inactivated scientist saw an under regulation of the AMPK and over regulation of the TOR pathways, this confirms the regulatory role of sestrin in these two systems. The pathological effects of a deficiency of sestrin can be seen in Drosophila as an accumulation in triglycerides, cardiac arrhythmia and muscle degeneration.  These same pathological effects can be seen in humans.  Finding a way to control these pathological effects could lead to way to greatly increase the human life span.

So how does this relate to me?

…besides all these cool pathways in my body that regulate how fast I will age?  If we can control the regulation of our TOR and AMPK signaling pathways we can control one aspect of our aging.  The end hope is that from this research scientist will be able to develop a way to slow aging in order to treat degenerative disorders, such as sarcopenia and Alzheimer’s. Since the beginning of time scientists have been searching for that fountain of youth.

A few critters in the animal world have found ways to combat the effects of aging.

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a tortoise exemplifies a model organism to study the mechanisms of aging

Maybe we should take a closer look at species such as orange roughy and tortoise that both have extremely long life spans.

By comparing protein profiles between long living critters and humans scientist may be able to unlock how their bodies

combat aging.  Their might be a time in the future when it is not uncommon to live to be over a hundred years old.

Oxygenated Water April 7, 2010

Posted by zach in Biology, Chemistry, Exercise, Medicine, Physiology.
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Does what’s in your water bottle during a race matter?

Recently a new study came out citing, when alcohol contained a high amount of dissolved oxygen there was a decreased hangover effect.  My first reaction was asking myself how this worked. From Science Daily I learned that dissolved oxygen can function as an agent for the alcohol metabolizing enzymes to oxidize the ethanol into less toxic products until it’s completely decomposed into water and carbon dioxide.  This sparked me to  research if any studies have been done to see if oxygenated water had an ergogenic effect in endurance athletes.

When mice consumed water with high dissolved oxygen content they had enhanced survival ability, fatigue recovery, greater anoxia function and increased energy storage.  While oxygenated water may contain what seems to be a rather insignificant amount of oxygen (~40mg/L) versus that which your body obtains per breath (~150 mg of oxygen), it may be just enough to tweak certain athletic performances.   Consider for a moment that you are a professional cyclist and the difference between  winning a race and going home a loser comes down to a few inches in a races that covers over 100 miles.  In these situations athletes are more than happy to look into any slim performance enhancing drinks, especially if it was as simple as drinking water with high oxygen content.

Thus in regards to the article, all the ergogenic effects of drinking oxygenated water that were found in mice would be extremely beneficial to any athlete. The studies are lacking in humans and there a lot of skeptics on the issue of oxygenated water.  The skeptics say that the oxygen in the water is insignificant because oxygen cannot be easily absorbed thought the stomach.  Secondly most of the oxygen gas will be burped out not allowing it to be absorbed into the body.  My reaction is if it worked in mice there is a good chance that the same effects could be carryed over in humans.  Both are mammals.  Both have similar digestive tracts.

Does the next step in athletic performance, in regards to oxygen intake, involve not breathing air but ingesting it?

Perfluorocarbon can contain 25 percent more oxygen than air and can transfer oxygen to the lungs three times more effectively than air. When mice are submerged in perfluorocarbon they can survive for several weeks and will make a complete recovery when the perfluorocarbon is drained from the lungs.  Amazingly, if a deep-sea diver used a single breath of liquid oxygenated perfluorocarbon, he or she could remain submerged for up to an  hour without  having to take another breath.

If oxygen uptake was no longer a limiting factor on athletic performance, then  a whole new set of possibilities emerges exploring  how fast or strong athletes can become by not breathing air, but breathing liquid perfluorocarbons.

The BBC production Wonders of the Human Body explores how perfluorocarbon have the possibility to be used as a new medium for the body to obtain oxygen.

The Full Story Behind Antioxidants February 12, 2010

Posted by zach in Biology, Chemistry, Exercise, Health, Nutrition, Physiology.
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A recent article out of Kansas State University by Steven Copp shows that antioxidants may not be everything the media has hyped them up to be in being able to increase muscle performance.  Their data shows that in certain cases when people supplement antioxidants they can actually impair muscle function. While antioxidants at certain dosages may be considered an ergogenic aid, there has been a large amount of media hype which has attributed to their recent growth.

Copp found that antioxidants can have an effect on the blood flow in the muscles.  This is possible by antioxidants decreasing the concentration of oxidants in our body.  This all sounds good, but hydrogen peroxide which is naturally occurring pro-oxidant in our body is a vasodilator. In short when you supplement large quantities of antioxidants you are drastically decreasing oxidant concentration in your body, this in turn can cause your veins to constrict from a lack of vasodilators, which limits the amount of oxygen to your muscles.  This effect can lead to changes in key signaling mechanisms that can also have adverse effects on functioning muscles.

With all this being said it’s not that you should stop eating antioxidant rich foods.   Researchers are still looking at the full physiological effect of antioxidants on exercise training.  What the researchers are saying is you have to consider your antioxidant pro-oxidant balance.  Next time you are at the store and see antioxidant supplements claiming to have extraordinary effects, you may want to look at the science behind what you are buying before you buy a supplement that has a null effect on your muscle performance.

Full article on Science Daily

Antioxidants at work