Intro is DONE and now onto the discussion!!!!!

Well, I impressed myself.  21 pages of intro and could have written more.  Should I have…probably not.  I did not even try to fuse the topics of adipose tissue and epigenetics and instead I’ll let them stand on their own.  I think in the end I have about 170ish references just in the intro.  When I fuse that with the 4 middle chapters and discussion I should get over that 300 mark easy.

What I am most happy about is how I just was getting into a groove.  Writing was coming easy, which the first draft should.  Of course I wrote all of it without spending some serious proofing time and I’m sure when I come back to it in a couple of days that some major changes will take place. I think the overall flow, concepts introduced, and depth into the literature should be solid and with some proofing will actually be entertaining.

Today, in one day, I pretty much cranked out my discussion for chapter 5.  Instead of 1.5 pages/day I seem to be able to move it up to 3 pages/day if I really have a handle on the flow of ideas before I actually start writing.  It is almost easier to write what you know, put in a few % this or transcription factor X,  and then go back for the references and details.

As I turn to the discussion my major goal is to speculate and try to tie adipose tissue metabolism and skeletal muscle epigenetics together.  Well at least one of my goals is to speculate.

Onto the Intro

Well I am not quite done with Chapter 5 yet, but oh well, I need to get started on the intro.  Hopefully I can work on both of these at the same time.  Today I have been organizing so that I can really write this intro as efficiently as possible.  One interesting thing of note is that I see intros ranging in length from 12 to 35 pages.  My goal is to keep it on the 12 side of things.  The plan of attack is to write in a wordy fashion and cut and slash to a tight 15 pages.  Ready, set, go…

Chapter 4 – Effects of daily voluntary wheel running on visceral adipose tissue mitochondrial content in Otsuka Long-Evans Tokushima Fatty rats

Well I have finished Chapter 4 on schedule.  Now it is on to a completely different topic for chapter 5.  The effect of exercise on epigenetic changes in skeletal muscle of mice.  This project was a high impact, high reward, high risk project that the funding agencies loved.  I received an American Heart Fellowship and 5K of research money from the American College of sports medicine to help with research.  The funny thing is, this is an on going project and I will not be done with it by the time I turn my dissertation in.  As long as chapter 4 gets accepted into a journal then I will be fine.  Alright, I have 10 days to finish this chapter.  Time to get to work.

Dissertation Timeline

So I have set an ambitous timeline for finishing up the dissertation.  Just thought I would put it out there.

Chapter 4 – finish rough draft of manuscript and get it to other co-authors by Feb 20th

Chapter 5 – Write up what I have on epigenetics project (will undoubtley not be completed with the data collection, which will likely not be added initially) by March 3rd

Introduction (chapter 1) – Finish by March 14 th, 10 days to write an intro.  Ouch that is going to hurt

Discussion (chapter 6) – Where I learn the art of hand waving in written form, finished by March 28th.  Also apparently the last time in my science career that I really get to speculate.

Edit-Appendixes – Gotta be done by April 9th.

Should be a real enjoyable 8 weeks (minus a day)

T-minus 55 days…and counting

Do you Know an Exercise Molecular Biologist?

Well, most people have heard of an exercise physiologist, but not so many people have heard of an exercise molecular biologist.  Since exercise is undoubtedly an important (maybe the defining) physiological stress it makes sense for a lot of physiologist to attach that moniker to their title and use exercise in their research.  Molecular biology on the other hand, not so much.  Defined by wikapedia as

Molecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interactions between DNA, RNA and protein bio-synthesis as well as learning how these interactions are regulated.

While physiologist are looking for interactions between organs in a whole organism, molecular biologist step it down a notch to looking for interactions within single cells.  For molecular biologist the idea of studying exercise is a foreign as the idea of studying protein 3D structure is to an exercise physiologist.  They just don’t overlap…or do they.  It is my belief that exercise, being the quintessential organismal stress, must have genetically conserved and molecular pathways that are activated within each cell.  One major problem to using exercise in molecular biology is the lack of good models.  Apparently its hard to get cells to exercise.

Although it might be hard to get cells to exercise the principles of exercise are applied to the most basic of molecular biology on a regular basis.  With such a small and easily manipulated genome the yeast became the standard organism to study the most basic principles of biology such as protein trafficking, cell signaling, and organelle interactions.  One of the most common ways to manipulate the yeast environment is by switching the energy source in the media around the cell.  That simple switch from glucose to fatty acids is not unlike what occurs with an extended bout of exercise, and the interesting thing is that yeast respond in a similar manner as we do, ramping up the metabolic processes necessary to use fatty acids for energy.

Another example is one that I heard recently by a senior investigator in the Life Science center concerning knockout mouse models and exercise.  It is common practice to knock a gene out of mouse and just look at how the phenotype differs from that of a wild type mouse.  Sometimes dramatic changes occur, and sometimes nothing.  Several mouse models where a gene beilieved to be involved in skeletal or cardiac muscle function have shown no adverse phenotype initially…that is until they exercised the animals.  Sometimes a paper claiming that no phenotype exists is even published before the animal is exercised and the phenotype revealed.  The fact is that exercise invokes a fundemental stress response in the animal, which can bring out the function of a gene previously unknown.  In this case exercise is more than science that is good for you, but good science as well.

Dissertation Time

In months I will be handing in my dissertation to my committee.  Two weeks after that will be my oral defense, and the day after that I close on my house.  So much happening in so little time and yet now I chose to update the blog.  I hope to continue to use this blog as an outlet for the struggles that I will undoubtedly have over the next two months.  So for my dissertation I have the 2nd, and 3rd chapter written, but will need to spend a day or so editing the format so that it works in the dissertation document.  That really leaves the following writing:

Chapter 1 – Introduction – probably 25-30 pages

Chapter 4 – Adipose tissue mitochondria in response to obesity and physical activity (15-20 pages)

Chapter 5 – Epigenetic changes during voluntary running on a high fat diet in mice (15 – 20 pages), although I have a pretty good intro written already

Chapter 6 – Discussion – probably 15-20 pages.  This is really going to be a bitch to try and organize such a wide range of topics into a cohesive intelligent and thought provoking chapter.  A challenge my committee wants me to do.

Appendix(s) – lots of unpublished data going in to the pad the the thickness.  Probably an extra 15-20 pages depending on the depth of discussions, methods, and intros.

So in summary I need to write about 85 – 105 pages (while citing over 200 papers for sure) in 2 months while continuing to do research for the month of February.   At least it is double spaced.

to be continued….

Running a Marathon Won’t Kill You

Big surprise huh? The New York Times recently published an article about a new study showing that you are 2 times more likely to die driving a given marathon course compared to running it. This new study is published in the British Medical Journal (BMJ), which is the equivalent of the Journal or American Medical Association (JAMA).

It is funny how people so often worry about the fact that you could have a heart attack while running, yet the consequences of everyday activities like driving are never given a second thought. Normally the press will really play up the fact that someone died while running, while traffic related deaths have become such an ordinary part of life. I am not so biased that I don’t the irony in the fact that people can die while doing something that is good for you, but I think it speaks to how little we really know about the biolgical mechanisms by which exercise actually protects our health.

For example, there is plenty of evidence to suggest that your risk of a cardiac event does go UP while exercising relative to just sitting there. Of course there is also an overwhelming amount of evidence pointing to the least fit individuals being twice as likely to die from any number of a diseases (diabetes, cardiovascular disease, etc.). A paradox, perhaps. I look at more like a detective, what is it about continuinal increasing your risk and stressing your cardiovascular system that keeps it healthy. Much like the idea that you can “precondition” tissues to be able to better handle a subsequent similar stress the same is true with exercise. Short small bouts of stress are most certainly healthy for you.

So if you are thinking about running a marathon, don’t let your health risks stop you. Instead let the desire for good health drive you. Your body will thank you in the long run.

Systems Biology…I Think You Mean Physiology

So this past week there have been several really interesting and opposing articles related to the term systems biology. Just last week my mentor, who frequently get excited, was talking to me about how reductionist (ie the molecular biologist interested who continually put out papers in the one gene – one disease frame of mind) have attempted to hijack the disciple of physiology by calling it systems biology.

To get a better understanding of the history of these terms lets use our good friend goggle. Founded in 2000 the Institute for Systems Biology is located in beautiful Seattle Washington. This is the definition of systems biology that they use on their website,

 

Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. Instead of analyzing individual components or aspects of the organism, such as sugar metabolism or a cell nucleus, systems biologists focus on all the components and the interactions among them, all as part of one system. These interactions are ultimately responsible for an organism´s form and functions. For example, the immune system is not the result of a single mechanism or gene. Rather the interactions of numerous genes, proteins, mechanisms and the organism´s external environment, produce immune responses to fight infections and diseases.

Now lets move to a definition of physiology from the American Heritage dictionary.

phys·i·ol·o·gy play_w(“P0278400″)

 (fz-l-j)

n.

1. The biological study of the functions of living organisms and their parts.

2. All the functions of a living organism or any of its parts.

Alright so yes the definition of physiology is somewhat broader, but nevertheless it covers what is mentioned in the definition of systems biology.  Perhaps because it is not explicitly stated in the definition of physiology that the parts of organisms can be studied in an integrative manner.  Maybe this is why integrative physiology departments and meetings have popped up in recent years in concert with this idea of systems biology.  However, physiologist have been studying the multiple organ systems (in physiology we call systems organs) for as long as the field has been around.  In fact in 1964 C. Lad Prosser said the following,

…the net effect of the new knowledge now emerging in physiological genetics is to provide a cellular explanation for the adaptive interactions between the environment and the organism.”

To me this is unbelievable that he had the foresight to recognize the potential for examining the ways that genes can help explain adaptive changes in the organism (ie in systems).  The words physiological genomics only appeared on pubmed in 1998 a mere 34 years after Prosser’s insight.

Physiologist were interested in exploring how the gene-environment interaction affects the organism as a whole quite a bit earlier than systems biologists were.  Now just as my boss has been upset with the way former reductionist have attempted to take over physiology by a new name other have become upset as well.  In recent introduction to a series of reviews pertaining to performance in the Journal of Physiology Micheal Joyner and Bengt Saltin don’t hold back in their final paragraph stating

One general conclusion from all of the reviews and papers is that the main regulatory and adaptive responses to acute and chronic exercise defy simple reductionist explanations. A more provocative conclusion is that before the reductionist community naively concluded they needed to reinvent and rename physiology in the guise of ‘systems biology’, investigators interested in exercise were already committed to understanding the interactions of key biological responses at multiple levels of organization and integration. An even more provocative conclusion is that the systems biologists have much to learn from the successes of investigators interested in exercise and even more to learn from their continuing questions

 I very much agree with Joyner and Saltin.  It is true that they have much to learn from us and that many important and interesting questions remain to be solved.  Of course this was published in the Journal of Physiology where the main readership is, yep you guessed it, physiologist.  For this message to hold physiologist need high impact papers and commentary in journals with a high impact.  Of course this becomes more difficult when nature publishes a recent article discussing the advantages to using a systems biology approach rather than a physiological approach to study aging.   Of course aging is a physiological process, clearly without a single gene responsible for its pluripotent effects.  It is a question that physiologist have been attacking for decades using a variety of multiple system approaches (ie animals and humans).   What is really striking about this article is the great lengths that the author, Thomas B. L. Kirkwood, takes to avoid using the word physiology.  Is it such a bad idea to claim to that taking a physiological approach to studying aging is such a bad thing?  After all we accepted the role that genetics would play in physiology a long time ago.  Isn’t it about time that the reductionist recognized that they have much to learn by framing their studies in a physiological light?

Even for those not interested in exercise from a health standpoint it is still a useful physiological tool to study the gene-environment interaction.  Here is the example that I like to give about why using exercise in any phenotyping study is necessary.  Blood flow is capable of increasing 40 fold with exercise in working skeletal muscle.  An animal knockout model might display a phenotype where blood flow increases (or decreases) 5 fold.  While that is interesting in itself it still tells us nothing about the capacityof the system.   After all a few muscle contractions could normalize the blood flow, but you won’t know unless you test the system at max capacity, ie exercising.  All these genetic knockout models take a very narrow view of the gene-environment interaction and hardly ever attempt to use exercise to rescue the phenotype despite its pliotrophic effects. 

Hopefully systems biolgist will come to their senses and join physiologist in studying the complexity of how organisms adapt to their environment.

Life Evolved With the Help of Physical Activity

So here is an idea that I have been thinking about. It all started with my mentor, Dr. Booth, getting really excited about a paper in 2006 by Raymond and Segre appearing in Science. Although the details were difficult to understand his interpretation was clear, physical activity was key to the development of complex metabolic pathways early in life.

Here is the jest of the argument. Once photosynthesis evolved in bacteria (the process of using sunlight, water, and carbon dioxide to make energy and oxygen) the amount of gaseous oxygen in the atmosphere increased dramatically. Back then oxygen was toxic to most organisms and there were multiple was organisms could respond to this rise in oxygen. They could 1) Hide, 2) Adapt, or 3) Perish. Well a group adapted (likely by chance since evolution is not forward thinking) by being able to use oxygen as the final electron acceptor in aerobic respiration. The consequences of this cannot be understated, oxygen with a huge electronegative potential allowed for 4 times as much energy produced from a molecule of glucose over any other currently used final electron acceptor.

All of a sudden organisms had all this extra energy without having to do anything. Naturally they starting to use this energy for a wide variety biochemical reactions that previously were too energy costly. This is what Raymond and Segre showed, adding oxygen greatly increasing the number and the complexity of biochemical reactions possible. Genomes became more complex, behaviors became more complex, and the diversity of life exploded. It is easy to visualize that being more motile (of physically active) would have allowed organisms to obtain energy easier and avoid predators easier. With their new found extra energy from aerobic respiration this likely happened. Once they became more physically active then the biochemical pathways for those actions would have further developed, meaning physical activity actually selected certain genes and behaviors to develop. Amazing.

It then does not come as much of a surprise that physical activity is important for our health today. Just think about it’s beginnings.

Bicycling for Health

This is from a post I made on my Low-Car Diet Blog and the orginal can be found at the Columbia Tribune’s website along with all of the other posts.

September 22, 2007

Why Biking Is Cool & Healthy

 

By Matthew Laye

One of the blogs I regularly read is called “No Impact Man” about a guy in NYC trying to reduce his impact on the environment. He blogs daily about the difficulties and advantages to this type of lifestyle. On Friday his post was entitled “Why Biking is Cool” and summarizes many of the same sediments that I have towards biking.

In addition to that little tid-bit I wish I could say have something of note to discuss, but life has pretty much gone on as normal.

However, seeing how I am a member of the Health Activity Center or HAC. I should really devote some time to posting about the dangers of being inactive and conversely some of the health benefits of being physically active. Physical inactivity increases the risk of at least 25 different diseases included;
Coronary artery disease (by 82%)
Stroke (by 150%)
Hypertension (by 43%)
Colon cancer (by 69%)
Breast cancer (by 45%)
Type 2 diabetes (by 100%)
Osteoporosis (by 144%)
YET…

25% of Americans complete no physical activity and 50% do not meet the Surgeon Generals recommendation of at least 30 minutes a day, most days of the week. Unfortunately the situation is only getting worse.

Here is an extended list of facts about inactivity related desease compiled by researchers against inactivity related diseases.

* 26 unhealthy conditions form the syndrome. (click here to view these conditions)
* One in 10 deaths is premature due to SeDS.
* The cost of sedentary-related conditions is $1.5 trillion over the next 10 years.
* Children are now getting adult-onset (type 2) diabetes
* 60% of overweight children have at least one cardiovascular risk factor.
* Many adolescents who are in the top 30% projected in body weight are already pre-diabetic.
* Children watching 1 hour of TV a day have less obesity than those watching 4 hr a day.
* Three out of four adults are sedentary and candidates for SeDS.
* Adult-onset diabetes increased 5-fold from 1958 to 1996.
* Three days of complete bed rest produces a prediabetic blood sugar.
* Secretary of Health, Human Services, and Labor Tommy Thompson estimates that moderate exercise could prevent 5.8 million new cases of type 2 diabetes.
* The first observable defect in type 2 diabetes usually often occurs in inactive skeletal muscle.
* Adult obesity increased 57% from 1991 to 1999.
* The CDC has written in JAMA: “Clearly, genes related to obesity are not responsible for the epidemic of obesity because the US gene pool did not change significantly between 1991 and 1999.” Lack of exercise is an important factor.
* We are performing less physical activity than our ancestors, but our genes require us to be active in order to produce proteins that keep us healthy.
* It only takes 600 additional feet of walking each day by adults for the next 10 years to prevent adding 10 pounds of fat. The distance to prevent adding 10 pounds of fat in the next 10 years for 7- and 15-yr olds is 1200 and 730 feet, respectively, as kids have less weight to carry.
* Physical activity reduces colon cancer by 50%.
* “Bad” blood lipids are removed from the blood after moderate physical activity.
* The increase in type 2 diabetes at age 65 yrs is largely due the decrease in physical activity with aging.
* The 43 million without health insurance will not have access to expensive gene therapies, tissue replacements, stem cell therapies, etc. The highest frequency of chronic diseases occurs in the lower income group. An appropriate approach would be to practice primary preventive medicine including 30 minutes of moderate physical activity each day.
* Moderate physical activity lessens the incidence of the decline in female cognitive function with aging.
* The average American was expected to spend 2.28 yrs during their lifespan in a nursing home in 1985. A program of physical activity that would delay their entry to nursing home by 1 year would save $50 billion.

(Sedentary is defined as less than 30 minutes of moderate physical activity, equivalent to brisk walking, each day). Information is based upon US statistics.

Certainly there are some scary facts there. No matter what each of our reasons for going low car, be it practical, environmental, economic, or health related, it is obvious that we all can benefit from this type of lifestyle.