That feeling in your stomach…

Emotions make us human. They guide most of our daily activities one way or another. Yet the scientific study of emotions is always a bit fuzzy, because they are hard to quantify and experiment on. Even though the following PNAS paper from researchers in Finland suffers from lack of objective quantification,  it is still a decent effort in answering a basic question about emotions. I will summarize and discuss the paper after the link, but the paper is also freely available in case you would like to read.

Nummenmaa L, Glerean E, Hari R, & Hietanen JK (2013). Bodily maps of emotions. Proceedings of the National Academy of Sciences of the United States of America PMID: 24379370

The question this study aims to answer is “Do emotions map to specific parts of the body?”. Nummenmaa and colleagues first asked human subjects to indicate which parts of your body responded to certain emotions (e.g. sadness, happiness) by coloring on a diagram. Averages over multiple subjects showed statistically significant locations for different emotions. For example, in response to “Anger”, answers showed activation around the head and the arms. You can see where other emotions are “felt” by downloading the paper. It is Figure 2.

Of course, this brings on a dilemma. We culturally assign locations to feelings. “Love” for example, we know, is felt in the heart area. So, the subjects might have given the answers they have due to their cultural conditioning. The researchers controlled for this by including subjects from different cultures (Swedish, Taiwanese) and have seen that feeling locations still correlated with each other.

The researchers also induced feelings non-verbally through images and observer similar localizations. I think this control still has some drawbacks. Even though the emotion wasn’t spelled out, the subjects could consciously identify what they are supposed to be feeling and biased their answers. Still, repeats are always welcome.

A few more experiments were included in the paper, but they are of similar nature (a subject indicates “where” the feeling is) and therefore have the same strengths and weaknesses. The authors mention towards the end of the discussion that this kind of study would benefit from newer imaging techniques.

To be honest, I was expecting to get more out of this paper after reading the abstract. I don’t know, maybe something like “Second right toe responds to grief”. It would have opened the door to new neurological studies and explained how acupuncture works. Alas, we are not there yet. Hopefully next time.

Walking fast in Manhattan

Today I attempted to solve a walking related question that has been bugging me for a while. 

Let me give a bit of background and then I will get to the question: 

For those of you, who haven't been to NYC before, one of the prominent features of the city is the long North-South avenues. These start in Harlem and go all the way downtown. Numbered streets cross the avenues at constant intervals.

Traffic on most North-South avenues flows in one direction, uptown-bound (North) or downtown-bound (South). Traffic lights on these avenues are set to switch in a wave rather than synchronously to minimize interruptions. Once you catch a green light, you ride the wave and as long as you can keep a certain speed, you travel a good number of blocks before seeing a red light (it is a whole different story if someone hails a cab in front of you, but we are not dealing with that here).

Of course the lag between the lights is optimized for car speed. If you are a slow-moving pedestrian, riding the wave is not a realistic option. You will unavoidably hit the red lights more often, because the wave will be long gone by the time you get to the next light. Unless you are slow enough that the next wave comes and catches you. As a pedestrian you also have the option to walk against the traffic (on the sidewalk, of course) and there might actually be a case where this is the best option.

So, here is the question that formed in my mind during a 40 block walk: Assuming the red light is on for X seconds, the green light is on for Y seconds, there is a Z second lag between traffic lights and you are walking at P pace which direction should you walk in, with the traffic or against the traffic?

To be able to change variables and get a list of ETAs for different paces, I wrote a simulator using PHP. It basically advances from light to light, calculates the time, determines if the light is red or green and calculates how long the total trip will take. I tested the numbers it turned up to see if there are any bugs. I couldn't find any, but if you think there is a mistake, let me know.

In this first blog post I will keep the light variables constant. I am not patient enough to wait at the corner with a stopwatch and measure how long it takes for the light to switch, so in order to get a rough idea, I counted seconds in my head while walking. Based on this highly unscientific measure, red and green lights each are about 45 seconds. There is a 5 second blinking red light period, which I lumped with the green, because the NYers treat it so. The lag between two lights is about 5 seconds. 20 Manhattan blocks make up 1 mile and that is my assumed trip distance.

The numbers can be seen on this table below. You have your speed, your pace on the left and total trip time, red lights hit and total wait time if you go with the traffic or against the traffic on the right.

As you see, for car-like speeds going with the traffic is much faster than against (and safer, if I may add). The slowest speed where going against the traffic becomes advantageous is 6 min/mile. However, the window there is pretty small. You have to hit a 6-6.5 min/mile pace consistently. The 11-18 min/mile pace range, which most regular human beings fall into, is divided into two. If you are on the faster end of the spectrum (ehem!), walking against the traffic saves about 20 percent; if not, it can be disastrous.  

Whichever way you are traveling, one interesting outcome is that there are vast speed ranges, where walking faster doesn't get you to your destination quicker. In fact, if you attempt such a North-South walk in Manhattan you will end up passing some people only to see them again at the next traffic light. It is very uncomfortable until one of you turns to a side street. (a little note here. These numbers are equal, because you come to a red light at the end of the last segment and you wait to cross it. If you ignore that red light, there are very small differences, because you traveled the distance between the last two lights faster.)

If I can get a chance, I would like to test different light lags to see what value would be the best to speed up pedestrian traffic. That will be the next post. Until then, walk carefully and let me know about your results if you give this a try.

Traffic light photo from Fotopedia.

What does "different" mean anyway?

Your traditional scientific article title is pretty drab. Simply a jumble of big words and strange acronyms to anyone outside the target audience. Yet every now and then you get a good one. Like this paper from Germany, which proudly claims that “Ultra-Marathon Runners Are Different”

Freund W, Weber F, Billich C, Birklein F, Breimhorst M, & Schuetz UH (2013). Ultra-Marathon Runners Are Different: Investigations into Pain Tolerance and Personality Traits of Participants of the TransEurope FootRace 2009. Pain practice : the official journal of World Institute of Pain PMID: 23368760

Didn’t we know that they were different? I am embarrassed to call myself an ultra-marathoner, since I have only done two road 60K’s, but my girlfriend has already labeled me “crazy”. And then there is Scott Jurek and Ellie Greenwood and Mike Morton and many many others. People who run a race that was intended for horses. People who run from the lowest point in the continental US to the highest. In mid-July! Yes, of course we knew they were different, but I guess it is good to have some scientific backing and define what “different” actually means.

To study the “different”, Dr. Freund and his colleagues picked a great recruitment spot: TransEurope Footrace. It is not an annual race and thus is not well known. It has been held in 2003, 2009 and 2012. This paper deals with 11 people who ran the 2009 version of the race, which consisted of 64 stages run over 64 days totaling 2789 miles (4487 km, it is a pretty big continent that Europe).

The researchers went for the obvious question first: "Is there a difference in pain tolerance between the runners and controls?" The way they tested this was by dipping the subjects' hands in a bucket full of ice water and asking them to rate the pain level every 10 seconds for 3 minutes. The runners reported less pain compared to controls. This seems like a straightforward experiment and a clean result. My only worry is that runners might have developed tolerance in their hands, because they are often exposed to harsh weather conditions. In other words, this result may not be due to a general tolerance to pain. Confirmation with an alternative method would have strengthened the conclusion (maybe a slap on the face? I don't know).

On the psychological end of things, the authors put the runners and the controls through a General Self-Efficacy Test (GSE) and Temperament and Character Inventory Test (TCI). Somewhat surprisingly, GSE didn't show any differences between runners and controls. People who score higher in this test are expected to overcome more challenging tasks. But again, just because the controls didn't run 2000+ miles, doesn't mean that they are slackers. They could very well be tackling tough issues in the non-exercise realm.

On the TCI test, the runners came out less cooperative, which is something I have a hard time believing. Everything I heard so far about ultra-runners point in the opposite direction. Runners scored higher in self-transcendence and self-forgetfulness categories, which is understandable.

All in all, this paper suffers from having a small number of subjects and a limited number of tests. I do understand though. Finding subjects for this kind of work can't be easy. Neither would it be easy to convince them to sacrifice their running time to go through tests.

Despite my joking early on, I do think these folks need to be studied. They clearly exhibit certain characteristics at the extreme. Maybe not all, but at least a few of these characteristics, like perseverance and adaptability, are highly desirable. Understanding what makes ultra-runners tick at a more detailed, even at a molecular level, would help us regular humans develop these skills.

Exercise and neurodegeneration

A lot has been said about the positive effects of exercise on healthy brains, but things are less clear in the disease state. In the following paper, John D. Fryer and colleagues studied the effects of exercise in one specific disease, SCA1 (SpinoCerebellar Ataxia type 1).


Fryer JD, Yu P, Kang H, Mandel-Brehm C, Carter AN, Crespo-Barreto J, Gao Y, Flora A, Shaw C, Orr HT, & Zoghbi HY (2011). Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science (New York, N.Y.), 334 (6056), 690-3 PMID: 22053053



SCA1 is one of the polyglutamine diseases. As explained here, poly-glutamine (aka poly-Q) diseases result from an extension in the poly-glutamine region of the causal protein. In SCA1 the causal protein is Ataxin-1 (shown below, image from wikipedia). Healthy individuals have a 6 to 35 long glutamine stretch around the middle of Ataxin-1, while individuals carrying the disease have 49 to 88 glutamines. This extension causes a change in the function of Ataxin-1, which in turn results in the death of specific neurons (neurodegeneration) and finally loss of motor functions.

So, theoretically, delayed neurodegeneration should delay the onset of symptoms. (side note: The surviving neurons might also be dysfunctional, but that is a separate discussion). This is where physical exercise comes in. Exercise has been shown to increase the production of neurotrophic factors. These factors, like BDNF or EGF, increase the production of new neurons and keep the existing ones alive and improve quality of life for the patient.

Of course biology is never that simple. Poly-glutamine proteins work on multiple levels and so does exercise. It can be beneficial for one system (e.g. by expressing neuronal survival factors), while taxing another beyond its limits (e.g. by increasing production of free radicals). In one mouse model of Huntington's Disease (another poly-Q disease) exercise has been shown to worsen symptoms.

In order to solve this dilemma empirically, the researchers put a mouse model of SCA1 on a mild exercise regimen (5 times a week). No improvement in motor performance was observed, but exercised mice lived about 15% longer than the controls. They could have called it a day there and went to publish their results in a lower journal, but Fryer and colleagues wanted to understand how this happened on a molecular level. This is very crucial. After all, mice are mice and they might be surviving longer for a reason, which might not be applicable in the human body.  

The researchers found that a neurotrophic factor, EGF, was expressed at a higher level in the brainstem of mice in response to exercise. EGF in turn decreases the expression of another protein called Capicua (Cic). To bring things full circle, the researchers showed that decreasing Cic levels in disease carrying mice through genetic means increases survival just as exercise does.

The paper doesn't present any human data. So, it is hard to conclude that same results will be observed in exercising patients (especially in a brain related disease). Hopefully, further research into the subject will provide an answer soon. Recommending exercise to pre-symptomatic patients would be a quick impact of this study. Designing a drug to mimic the molecular effects of exercise (lowering Cic levels or activity) would surely take years, but would improve many more lives.

Are you addicted to running?

I might be pushing the limits of irony by posting about running addiction so soon after an ultramarathon, but this paper has been sitting on my desktop for a while. So, here it is:

Chapman CL, & De Castro JM (1990). Running addiction: measurement and associated psychological characteristics. The Journal of sports medicine and physical fitness, 30 (3), 283-90 PMID: 2266760

People sometimes jokingly say that they are addicted to running. Like anything that makes you feel positive, an addiction to running sounds plausible. I went looking for some research on the subject and this paper from the last century came up. (By the way the paper wasn't available from the journal's site. Guess where I found it.)

Drs. Chapman and Castro from Atlanta GA set out to define a set of questions to be used to determine if someone is addicted to running or not.

A previous study had created a metric called  "Commitment to Running" (CR) score. However, the authors make a distinction is between "addiction" and "commitment". Addicted people feel like they have to run whatever injuries or other problems it might cause. Committed people, on the other hand, have a drive to continue running, but they are in control. In other words, running everyday doesn't necessarily mean you are addicted. (Did you hear that family and friends?)

To measure "addiction", a small number of people (n = 52) were asked to score given statements on a 5 point scale (as in "Strongly Disagree" to "Strongly Agree"). The statements that correlate well with the self reported level of addiction includes: "I run on a regular basis", "I would run with intense pain", "I would not reschedule activities with my friends in order to run" (The last one probably is scored in the opposite direction. i.e. if you "strongly disagree" it increases your final score (RAS: Running addiction score)).

The small size of the study and the self reported level of addiction leaves a lot of room for variation. Yes, the 11 accepted questions seem like they would measure the level of running addiction, but so do some of the 7 questions that didn't make it into the final test, because the correlation was low. For example the statement "I think of running when I am doing other activities, such as working" did not correlate with running addiction in this group.

Diving deeper into the details, the authors claim that for men, RAS correlates well with self rated addiction as well as the commitment score, while for women it only correlates with addiction. To simplify, for men commitment and addiction are similar, for women not so much. This would mean so much, only if they had a few hundred men and women instead of 37 and 15 respectively.

In the last bit of the paper the authors analyze personality traits of runners, but I am not going to go into detail. You can read the full paper if you wish.

This paper points to the gold mine, but doesn't really take us up there. Now that we have an endless source of subjects, it might be time to do this on a bigger scale. All you need is a few volunteers, a few clipboards and an NYRR race. And who knows, maybe one day we will see it on the cover of Runner's World: "Are you addicted to running? Find out in 10 questions!"

Geron exits stem cell research

Geron exits stem cell research

I am looking for details, but this is grim news. Geron was heading the push in bringing embryonic stem cell research to the clinic.

Embryonic stem cell clinical trials

Human embryonic stem cell based therapies are slowly making their way into the clinic. Geron's spinal cord injury trial was the first of course and this one is still underway. Advanced Cell Technology is starting the second trial in the US, on Stargardt's Disease, an eye disorder.

I was at the 6th NYSCF Annual Translational Stem Cell Research Conference last week, at the Rockefeller University. The two day meeting included panels on how to move the stem cell research into the clinic and latest updates from the field. I won't repeat the unpublished data here, but suffices to say that the field is moving forward both in using stem cells as models of disease in drug discovery and producing cells and tissues to replace lost or dysfunctional tissue.

Peter Coffey from University College London was named the inaugural recipient of the Robertson Prize in Stem Cell Research. Their London Project to Cure Blindness deals with age related macular degenaration. He presented an excellent talk summarizing the current surgical methods they apply to improve the lives of people suffering from this disease and then he described how they plan to use tissue generated from human embryonic stem cells in this process. Pfizer is expected to begin clinical trials soon.
A Bridge to Cures: A NYSCF Short Film from NYSCF on Vimeo.

Did you do your run today? Really?

When it comes to physical activity, there are two kinds of people. There are those who love their daily run/bike/swim and those who avoid it at all cost. Folks in the first group probably are not aware of a thing called Department of Health and Human Services Physical Activity Guidelines for Americans (I am pretty sure it applies to other nationalities too). Don't look at it, you are probably overdoing it anyway. If you are in the target demo though (group 2), the document could be a good starting point.

So, how closely do people follow the guidelines? Three researchers, from Iowa, North Dakota and Washington D.C. set out to answer:

Physical Activity in U.S. Adults: Compliance with the Physical Activity Guidelines for Americans

The guidelines ask for a minimum of 150 minutes of moderate physical activity (75 if vigorous. Running counts as vigorous). When asked, people reported an average of 324.5 minutes of moderate and 73.6 minutes of vigorous activity. According to these numbers, 62% of adults were active enough, ergo all this obesity and heart disease and diabetes and such was caused by evil spirits. It was time to call the evil spirit department and pop the champagne.

Some smarty pants grad student probably came along at this point and said "hey, why don't we validate these results with some sciency gizmos and then we can pop the champagne". The kid was probably just trying to get a project going to guarantee his continued employment (and in this climate can you really blame him!), but we scientists just love gizmos and anything related to gizmos (even the word "gizmo") and especially those that are sciency. So, they did. With some accelerometers.

The results are truly amazing. Average duration of moderate activity fell down to 45 minutes, while vigorous activity was down to 18 minutes. Less than 10% of adults were following the guidelines.  

So, how did this happen? Were their accelerometers broke? Maybe. But looks like this is a commonly used method for measuring physical activity. Were people lying? I don't think so. Why would they? There is no incentive to lie here. What happens most likely is people who don't like to be active overestimate time spent walking to their car, the stairs they climb or the boxes they carry. Also, they probably count activities that wouldn't qualify. For example, for walking to count as moderate activity, you should be walking briskly.

What do we do then? Do we all get accelerometers? Not very practical. But paying attention to your routine for a few days, measuring how many steps you climb, how many minutes you walk around etc; should give a general idea. From there you can make improvements to catch the 150 minute goal (e.g. walking faster or taking the stairs for a few floors).

Also, please remember that there is no penalty if you exceed the recommended dosage. In fact, it is encouraged.

(image from Flickr)

Blocking HIV infection by breaking stem cells

Just because I am an embryonic stem cell researcher, don't think I am neglecting adult stem cells. Here's a good paper that combines the methods of gene therapy with the strengths of stem cell biology:

Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids

Hematopoietic stem cells are responsible for replenishing the entire hematopoietic system, which consists of multiple cell types including oxygen carrying erythrocytes (red blood cells) and of course disease fighting lymphocytes (white blood cells). What is amazing about hematopoietic stem cells is that a single one of them can recreate the entire system. This is mostly theoretical, but in practice a few cells are enough to accomplish the job. 

This feature of the hematopoietic stem cells is already used in cancer treatment. In some cases, some stem cells are removed, all the other cells killed with extreme treatment and then the patient's blood is replenished from the saved cells.

Next logical step is to use this to fix other blood diseases, like hemophilia. One could take some stem cells out, fix a few, inject them back to the patient after killing all the defective cells and the newly produced cells won't have the disease. This is exactly what the researchers did in this study. Only, instead of fixing broken cells they broke normal cells. Let me explain. 

Remember AIDS (Acquired ImmunoDeficiency Syndrome)? AIDS is caused by this virus called HIV. HIV infects immune system, lymphocytes die, immune system falters, patients can't fight simplest diseases and eventually succumb to one of these. However, HIV can't just go through the cell membrane, it needs a gateway of some sort to accomplish its evil goal. If one could find this gateway and break it, one could stop the infection process.

A natural experiment (a.k.a. a human being) provided the clue. Scientists realized that people, who had a broken CCR5 gene were refractory to HIV infections and they figured HIV needed CCR5 to enter the cell. Following this clue, Schleifman and colleagues broke the CCR5 gene in some human hematopoietic stem cells (we won't go into the details, but that is equally impressive) and showed that these cells and the lymphocytes they made were now resistant to infection. In their study they injected the cells into rats, but in a clinical setting this can be used to increase the numbers of virus-resistant lymphocytes and thus shore up the immune system.

I don't see any obvious safety concerns with moving this study to the clinics. No viruses were used and hematopoietic stem cell transplantation is routinely done. The major hurdle here will be the efficiency and the cost. Let's see how long it will take to figure that one out. 

The effect of pacers

The recent IAAF decision to only admit women's records when they are achieved in women-only events implies that women run faster when they are following a male athlete. The new ruling made Paula Radcliffe's two best times (2:15:25 in 2003 London and 2:17:18 in 2002 Chicago) ineligible. Fortunately, Radcliffe is insanely dominant in her field and has the third best time too (2:17:42 in 2005 London, this one eligible). I am certain IAAF wouldn't (couldn't) have taken this step if the name of the record holder had to be changed.

The running community, including Radcliffe, wasn't pleased with the change, because it made things more confusing. Radcliffe stated in a Runner's World interview that having pacers did not affect her performance. This recent paper somewhat backs her up on that.

The Effect of a Second Runner on Pacing Strategy and RPE During a Running Time Trial.

Bath D, Turner LA, Bosch AN, Tucker R, Lambert EV, Thompson KG, St Clair Gibson A.

The researchers asked 11 non-elite athletes to run 5K time trials with or without a pacer and varying the position of the pacer (front, side or behind the subject) and measured heart rate, analysed the athlete's pacing strategy and got feedback on how hard the run felt. They found that the presence of the second athlete did not affect the speed, heart rate or strategy. Only effect was on the perception of effort. Most runners reported that the run felt easier with a pacer.

Obviously this is only a 5K trial, a marathon is much harder to pace, but then Radcliffe or any marathon world record holder will obviously have the gift of perfect pacing other mortals don't have. So, this confusion might be pointless at the end.

Finally, here is my suggestion for the next split in the world records book: "Red lead car" vs "Blue lead car"

Side note: Congratulations to Patrick Makau of Kenya for his new World Record.

Running and the knees

My non-runner friends are often worried about my knees. They are very certain that running is very very bad for my knees and I will have to use a cane after my 40th birthday. Here is a study from Australia that seems to support this view:

Is physical activity a risk factor for primary knee or hip replacement due to osteoarthritis? A prospective cohort study.

Wang Y, Simpson JA, Wluka AE, Teichtahl AJ, English DR, Giles GG, Graves S, Cicuttini FM.

Wang and colleagues collected physical activity data from 40000 people and looked if they got a knee replacement in the future. Their results show that people, who are physically active are more likely to get knee replacements, but not hip.

I unfortunately don't have access to the whole paper, but I have a few concerns about the study based on the abstract. First of all, general physical activity level was calculated. Not supported (biking, swimming) vs non-supported sports (running, soccer etc.). This would probably affect the number of joint replacements. The effect of running could be positive ("constant stress strengthens the joint" hypothesis) or negative ("you are killing your knees, stop now!" hypothesis).

Another quirk of the paper is that the knee replacement risk falls with increased activity. People who are active 1-2 days a week are in higher danger than people who are active 3 or more days. This could very well be related to random variation, but if the data holds (and holds for an impact sport, like running), I think it supports the "stress strengthens the knee" hypothesis. If you think about it, people who don't run are in less risk, because they don't put any impact on their knees. People who run constantly are in less risk, because their knees are used to it. People in the middle, the beginners or weekend warriors who just decide go out and sprint on a whim are those that stress unprepared knees.

In any case, I am glad they didn't find any connection to hip replacements. I recently heard how a hip replacement operation is done and let me tell you, it is not pretty. Knee replacement is probably not too different, but no one told me about that yet! (and don't you dare!)

Runs with Cars

I live on the Upper East Side of Manhattan and the nearest running route to me is the East River Walk, where I do all my weekday runs. Unfortunately, this popular pathway lies right next to the FDR Drive, which actually is a highway, not a tiny a little drive. So, every time I go out there, I worry that I might be doing more harm than good by breathing car fumes.

I saw this paper while catching up on my running related reading today, which definitely did not help matters:

No exercise-induced increase in serum BDNF after cycling near a major traffic road
I. Bos, L. Jacobs, T.S. Nawrot, B. de Geus, R. Torfs, L. Int Panis, B. Degraeuwe, R. Meeusen.

One of the ways exercise improves brain function is through increased production of BDNF, a neurotrophic factor, i.e. a chemical that keeps brain cells alive (this handsome fella to the right). The researchers asked 38 volunteers to cycle in a clean room, which had minimum air pollutants; and near a busy highway, which.... well, you know. They then measured how much BDNF was circulating in their blood. They accept that this is not a perfect way to measure the amount of BDNF made in the brain, but it is an indicator. Measurements in the clean room were as expected: BDNF levels increased after exercise. Near the highway, on the other hand, BDNF levels stayed the same.

Even though the data shows only loss of benefits rather than damage, from exercising in polluted air, it is clear that something is not right (and after an hour of huffing and puffing I would like my BDNF please!). They don't speculate much about an underlying mechanism either. Obviously, this will be the subject of further study. (what is a limit for pollution for example. Since we can't do all our running in clean rooms)

For now, I think I am going to try to stay away from the FDR Drive more often, even if it means taking it to the treadmill. It isn't much of a running route these days anyway, with all the repairs going on. I looked for a way to follow air pollution measurements in the city, but most sources are for broad areas. I assume Central Park would have cleaner air, but I have no proof. If you know of a website that streams data from measurement stations, it would be much appreciated.

Engineers vs Scientists

An engineer says, "If it isn't broke, don't fix it"; a scientist says, "Is it working? Let's break it and find out how."

Running research - 06/08/11

I go through a lot of research paper abstracts everyday, mostly in my field of study (stem cell biology), but also about running. I never have enough time to write about them. So, here is what I will do. I will pick a few interesting looking abstracts and list the links from time to time.

I don't have access to full texts of all these papers, so I will put a warning at the beginning each time, mentioning that I didn't review the paper myself, I am just going by the abstract. The papers are, of course, peer-reviewed before publication.

OK? So here goes the first edition:

Athletic identity and disordered eating in obligatory and non-obligatory runners.

First of all, did you know that there is an obligatory exercise questionnaire? Looks like it measures how big an exercise-addict you are.

This study suggests that eating disorders are more prevalent among those who are addicted to exercise (that is, people who score over 50 in the aforementioned questionnaire).

Assessing cognitive impairment following stroke.

This group showed that exercise post stroke can help patients regain their cognitive abilities faster.

Personal Best Marathon Time and Longest Training Run, Not Anthropometry, Predict Performance in Recreational 24-Hour Ultrarunners.

And one for ultramarathoners. As the title says, your success in an ultramarathon is best predicted from your longest training run and your marathon PR. And here is the formula for it:

Performance in a 24-hour run, km) = 234.7 + 0.481 (longest training session before the 24-hour run, km) - 0.594 (personal best marathon time, minutes)

Gotta love statistics!

Another modification in the central dogma

How I miss the good old days. And by that I mean high school, when I first learned about the central dogma: DNA begets RNA begets protein. Protein does the job.

As molecular biologists dug deeper, more and more exceptions were revealed. They found that the same piece of DNA could make different RNA's; one RNA could be processed in multiple ways to produce different molecules; protein translation could start at different points; proteins themselves could be modified; DNA could be modified to change the amount of RNA made; tiny little pieces of RNA, some of which come from discarded parts of larger RNA molecules, could modify the amount of translated protein. The list goes on and on.

And now there is one more. In a paper published in Science, Dr. Cheung's group from UPenn report that RNA sequences can differ from the template DNA. The group reached this conclusion by sequencing on average about 2 billion bases of RNA for each of 27 individuals and comparing it to their genome. This kind of work would not have been possible just a few years ago, but in the age of high throughput (or next generation) sequencing ubiquity they are becoming almost regular.

The UPenn group has gone the extra mile to make sure what they are seeing is not an artifact. They used very restrictive criteria, resequenced some of the samples and even looked for peptides that are coming from the modified RNAs. All these controls favor the initial observation.

There is no mention of a mechanism yet, but the observations themselves are exciting. I can't wait to see how this story develops.

Carb-loading works

This one is from the "We already knew that" department: Those who had more carbs the day before a marathon ran faster.

The researchers compared 2009 London Marathon runners' carb intake and found out that those who ate more than 7 g carbs per kg of body weight (about 3.5g/pound) the day before the race ran faster and maintained their pace better.

This of course is not a proof of causality. Were the runners faster because they ate more carbs or did the faster (more experienced?) runners eat more carbs?

The study digs a bit deeper and adds gender, BMI and training distance as predictors of finish time.

Foods with low glycemic index improves running duration

According to this study eating lentils (or anything with low glycemic index) 15 minutes before a run might delay exhaustion, while eating potatoes (high glycemic index) spikes your blood glucose, but does not help with your time.

The exercise used in the study follows the pattern 5 minutes warm-up at 60% VO2Max, 45 minutes at 70% and then to exhaustion at 80%. I think this represents more of a tempo run rather than a long run, but it is still worth the try.

Immunogenicity of iPS cells

On the matter of the induced pluripotent stem cells (iPSCs) those of us in the stem cell research community are like babies who have met a large body of water; pool, ocean; for the first time. We want to jump in and play, but we also have some doubts.

iPSCs hold great potential. Like the embryonic stem cells (ESCs) they can become any cell in the body. Unlike ESCs, they are fairly easy to make and come with less ethical problems. ESCs can only be isolated from a very young embryo. iPSCs on the other hand are created through the manipulation of adult cells. A skin biopsy or blood sample can provide the starting material.

The hope is, once we learn more about these cells and how they differentiate, we can make patient specific iPSCs and provide the cells or organs required. A new heart, a new lung, muscle cells etc (PBSs Nova has a wonderful documentary on the subject). This technology kills two birds with one stone. First, no more organ transplant waiting lists. Organs can be made in the lab when needed. Second, no immunosuppression. In the current transplant protocols, the immune system of the patient is suppressed, because no donor is a perfect match and thus the transplanted organ is a stranger and a target for the immune system. An organ made from the iPSCs on the other hand is a perfect match and it will not trigger a response.

Or so we thought.

There has been a flurry of papers recently comparing the two types of pluripotent cells, the new technology, iPSCs and the gold standard, ESCs. Again and again the conclusion has been that iPSCs are a good replica, but there are differences. Dr. Yang Xu and colleagues from the UCSD bring up the most significant difference to date in their paper published in Nature: The immune system rejects the iPSCs more vigorously than it does the ESCs.

Here is what they did. They injected mouse ESCs and iPSCs into genetically identical mice. In theory, the cells are exactly the same as the host. Therefore, they should not trigger the burglar alarm and live happily. This is what happens with the ESCs. They are not rejected. iPSCs, however, are hunted and killed.

Obviously, this does not bode well for the plan outlined above. If the iPSCs will be rejected once we inject them, the immune system of the patient will need to be kept at bay like in the current protocols.

As you may know, there is a discussion in the US on whether to allow the use of federal grants for ESC research or not. Experiments to make patient specific ESCs using the somatic cell nuclear transfer (SCNT) technique has largely been abandoned since the invention of the iPSCs. Both because it is not easy and it requires the use of private funds. The most significant implication of this paper is that the iPSC technology is not a perfect substitute for ESC research and further research in both areas is still necessary.

One important question remaining is what would happen if one injected a differentiated cell type (heart tissue for example) into identical mice. Would tissues coming from iPSCs still be rejected more rigorously than those coming from the ESCs or would they be equivalent? In fact, I would argue that this is the more relevant question, because in future clinical applications only differentiated cells will be transplanted, not the pluripotent cells. In the paper, teratomas that come from the iPSCs had more immune cells crawling in them, suggesting the results would be similar for differentiated cells also, but I still think it is worth doing the experiment.

Formation of teratomas is a risk factor for the eventual transplantation of organs from pluripotent sources. So, if after these experiments we find out that differentiated cells from iPSCs are accepted as readily as their cousins coming from the ESCs, due to the decreased chance of teratoma formation, iPSCs might be the better source for patient specific tissue creation.

Science in crime dramas

TV dramas are notorious for their scientific inaccuracies and leaps in logic. Just a few weeks ago Dr. House cured his patient's MS with embryonic stem cells! That therapy is not even experimental yet, but it gave the writers license to use the religion vs embryonic stem cell battle.

Here is some real science from a peer reviewed journal, which may find a use in a criminal lab. The group analyzed the expression level of certain genes in some tissues of dead mice. The genes they picked are responsible for running our biological clock and they have different ratios at different points during the day (morning, afternoon, night etc.). The scientists showed that the ratios stayed the same after death, basically providing information about the time of death. The study is limited to mice for now and estimates the time of death in a wide range, but it is significant as a proof of principle experiment.

The question is will this ever be used in a crime drama or is it just too real?

Patrick Tam

If you have read or written anything on developmental biology of the mouse the name "Patrick Tam" is familiar to you. Here is a short interview with him published in the journal Development.