Friday, August 29, 2014

The Friday Five

Highlighting some of the coolest science news we’ve seen lately.

1. Big news in regenerative medicine this week: scientists have grown the first working organ in a lab (a functional thymus was generated from reprogrammed fibroblast cells).

2. It sounds fishy, but zebrafish are helping scientists study potential mechanisms underlying Alzheimer’s disease.

Zebrafish are excellent model systems that help scientists learn about development and disease

3. Another interesting development for Alzheimer’s disease this week. Studies have revealed that infusing the blood of young mice into older mice reverses some of the aging process. Physicians will soon be testing if blood plasma from people under 30 can alleviate the symptoms of Alzheimer’s.

Sorry, Barnabas, but drinking the blood does not work.
4. Better science, better pizza. Scientists set out to “quantify the pizza baking properties and performance of different cheeses”, and the results are described here. Have they found the perfect combination of cheeses? I look forward to trying…

5. Time for a coffee break? No doubt you are familiar with the trademark “coffee ring” that results from spilled coffee, which decorated many of the journal articles I read back when we used to print them out. Based on this study, the video below shows coffee particles in action, forming that characteristic ring.

Science quote of the week:

“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less” --Marie Curie

Contributed by:  Bill Sullivan
Follow Bill on Twitter: @wjsullivan

Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, & Wyss-Coray T (2014). Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature medicine, 20 (6), 659-63 PMID: 24793238

Yunker, P., Still, T., Lohr, M., & Yodh, A. (2011). Suppression of the coffee-ring effect by shape-dependent capillary interactions Nature, 476 (7360), 308-311 DOI: 10.1038/nature10344

Ma, X., Balaban, M., Zhang, L., Emanuelsson-Patterson, E., & James, B. (2014). Quantification of Pizza Baking Properties of Different Cheeses, and Their Correlation with Cheese Functionality Journal of Food Science DOI: 10.1111/1750-3841.12540

Bredenkamp, N., Ulyanchenko, S., O’Neill, K., Manley, N., Vaidya, H., & Blackburn, C. (2014). An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts Nature Cell Biology DOI: 10.1038/ncb3023

Wednesday, August 27, 2014

Is it really possible for someone to turn into THE HULK? Don’t make me angry.

We are obsessed with superheroes. Humans have probably shared this fascination with superpowers since the beginning. Some of us are born faster, stronger, smarter - causing the rest of us to wonder whether we can tap into some hidden superpower within ourselves. We love hearing stories of genius and watching talent shows, just to catch a glimpse of someone crossing the threshold of what we thought was the boundary of human capability.

Stanford biologist Sebastian Alvarado is no exception, but he is endeavoring to put some scientific plausibility behind some of our favorite superheroes. Take the Hulk, for instance. The Hulk is the muscular green beast that scrawny scientist Bruce Banner transforms into whenever he gets enraged. A lot of scientists can identify with Dr. Banner’s plight, and I have seen many undergo an analogous transformation upon reading their grant reviews.


How did Dr. Banner gain this blessing and curse? As a scientist, he was researching how people summoned extraordinary bursts of strength. Using himself as a guinea pig, he exposed himself to gamma radiation in an attempt to become stronger. There was no noticeable effect at first, but when Dr. Banner got angry, his skin turned green and his muscles burst out of his shirt. Since Dr. Banner is a good guy, the Hulk is generally a good beast, although somewhat messy. When the anger subsides, Dr. Banner returns to his modest, wimpy self.

The comic book tale prompted Dr. Alvarado to wonder:  is this even remotely possible? He addresses the question in the video below.

Let’s clarify a few of these points for those who might be less familiar with the concepts. First, gamma radiation blasts your DNA (chromosomes) apart. As Dr. Alvarado mentioned, there are enzymes that will “heal” the DNA, but it doesn’t always heal correctly, which might result in new genes (and the loss of other genes). Second, we are learning more and more that genes are regulated in a surprising number of ways. They are not merely binary switches that turn on and off, but rather they are controlled more like volume knobs. Epigenetics refers to the factors in your cells that have their fingers on those volume knobs.

We discussed epigenetics in a previous article covering Ozzy Osbourne’s genome; in the case of the Hulk, epigenetics provides an attractive means to account for how Dr. Banner can switch between Hulk and normal guy. Between transformations, Dr. Banner’s genes are not changing, but which ones are active – and the degree they are active – is changing. For example, epigenetic factors can crank up genes controlling muscle development when they receive a signal in the form of a stress hormone that increases during temper tantrums. As this hormone subsides, other epigenetic factors return the volume of those genes to their normal level. You can think of genes as the selection of music, but epigenetic factors are the DJs.
So what kinds of epigenetic factors are there? We are discovering a dizzying array of cellular components that can alter gene expression, which can result in changes in physical appearance, behavior, mental abilities, and more. It has long been known that chemical modification (i.e. methylation, delivered by enzymes called DNMTs – DNA methyltransferases) of DNA itself can shut down genes. DNA methylation marks are like orange construction cones blocking the highway. Scientists then discovered that histone proteins, which congregate in bundles of 8 to form nucleosomes, could also be chemically modified in several different ways. The nucleosomes give DNA the “beads on a string" appearance shown below.

This is your DNA, not a pearl necklace! The DNA "string" wraps around the "beads", which are nucleosomes composed of 8 histone proteins. Once thought to merely help package DNA, we now know these nucleosomes are major contributors to the regulation of genes on the DNA.

These proteins were long thought to be just scaffolding components for the DNA, but now we know they play a major role in directing the activity level of nearby genes. Numerous different chemical modifications, such as acetylation, methylation, phosphorylation (and more), can take place on multiple places of each histone protein. These may alter the binding between nucleosomes and DNA, making certain genes more accessible, or these modifications may form a cellular “code” that can affect gene expression levels.

Histones can also be moved, replaced, or evicted by epigenetic factors called SWI/SNF ATPases. As the name implies, these enzymes require energy from ATP to affect gene expression. More recently, it has also been found that small non-coding RNA molecules can regulate genes.

A summary of the major epigenetic factors that can regulate the "volume" of gene expression.

While these complex methods a cell employs to influence gene expression offer a potential explanation for how someone could temporarily become a Hulk, it is by no means probable. Most massive gamma radiation doses would destroy genes that are essential to survival. But it is fun to use cutting-edge science to put just a tiny hint of credence behind the superpowers. And even more fun to think that with enough knowledge we may be able to modulate epigenetic factors to treat disease or maximize human potential.

Contributed by:  Bill Sullivan
Follow Bill on Twitter.

Falkenberg KJ, & Johnstone RW (2014). Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nature reviews. Drug discovery PMID: 25131830

Haggarty P, Hoad G, Harris SE, Starr JM, Fox HC, Deary IJ, & Whalley LJ (2010). Human intelligence and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking. PloS one, 5 (6) PMID: 20593030

Monday, August 25, 2014

Chinese Food And The One Hour Dilemma

Chinese food is a staple of the American city. Here marks
the grand reopening of a restaurant in Albany, NY. OK, so
they don’t know the marketing angle so well. The interesting
thing to me is the name of the restaurant – CCK – which is
one of the satiety hormones implicated in why eating Chinese
food makes you hungry so soon afterwards.
Chinese food is one of America’s favorite meals. In the New York City metropolitan area there are more than 1783 Chinese restaurants. That’s one restaurant for every 250 Chinese people in the city.

Eating Chinese food can be spicy or bland, rice or noodles, but it's always filling. The problem is that you supposedly feel hungry soon after eating. Could it be a devilishly sly plan to get you to order more wontons?

The truth is that some people do feel hungry soon after a Chinese meal, enough people to keep the old saying in our lexicon.

The first published instance of the Chinese food dilemma was in a 1934 article in the Golden Book. Nowadays the problem is called Chinese Food Hunger, or CFH for short. Can we pinpoint why people get hungry after a plate of Chinese food before the next mealtime?

Getting hungry in scientific terms is an issue of satiety. A hunger problem is really a satiety problem; less satiety = more hunger. This idea led to the creation of a satiety index by Holt et al., in 1995, ie. just how full certain foods make you feel. The index uses the same number of calories of different foods and converts the self-reported feelings of fullness over time by the participants to a number scale.

Chinese food from different parts of China uses either rice or noodles as a starch. These carbohydrates have satiety indices of 130 and 119, respectively. Potatoes, on the other hand, have a satiety index of 323, the highest of any food tested. This leads to one hypothesis of CFH - Americans think Chinese food makes them hungry sooner because they're comparing it to potato based meals.

People have been eating fewer potatoes in the last 30-40 years, McDonald’s French fries not withstanding. This may account for why many people think we talk about CFH less than we used to. However, a 2013 study showed that despite the high satiety of potatoes, they didn't significantly reduce the amount of food that was consumed later as compared to other meals. So maybe it means nothing.

You can see that hunger and fullness feelings are well
controlled and complex. Basically, the more green input,
the fuller you will feel and the less you will seek out food.
This is just one of the ways our brain tricks us into wanting
the things that we need.
The regulation of satiety and hunger is controlled by many hormones. Several gastrointestinal hormones act in satiety. Cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1, oxyntomodulin – these all work to increase satiety and decrease food intake. Ghrelin, on the other, is produced by select cells of the stomach and pancreas and acts to decrease satiety and increase food intake. These signals are monitored and regulated in the hypothalamus and arcuate nucleus of the brain – the so-called hunger centers.

Leptin works in the opposite direction as ghrelin. Leptin hormone is produced by fat cells (adipocytes). It stimulates hunger when fat cells are being used as energy source, as when caloric intake is low. Leptin increases satiety when caloric intake is high - more leptin is put out by fat cells. Leptin also acts in reward centers; more leptin (more fat = a more fed situation) decreases the reward felt by eating food, and reduces the craving for reward of food. These are complex pathways.

So what is it in Chinese food that affects the levels of satiety hormones?

Monosodium glutamate (MSG) is a common whipping boy. People have said MSG is unhealthy, raises blood pressure, and is toxic. Some people really do have a bad reaction to MSG, referred to as Chinese Restaurant Syndrome (don’t confuse CFH and CRS).  In CRS, suffers show reddened skin, headache, chest pain, sweating, and numbness. But most people don’t have a problem with MSG and survive Chinese food just fine.

MSG can lead to facial flushing like on the left. However, the
reduction in MSG use has not eliminated the problem for
some people. In many foods, the MSG has been replaced with
another flavor enhancer called E635. This is a combination of
two ribonucleotides (IMP and GMP) with two sodium molecules
on each. E635 can lead to similar or worse problems as MSG in
susceptible people. The smile on the right is after she discovered
how to avoid her problem foods.
Still, the vast majority of Chinese restaurants have cut back on MSG. This is another reason why some people say that complaints about Chinese food making them hungry sooner have decreased – because MSG is the culprit and less MSG is being. Not a very scientific determination.

A study in 2011 showed that MSG does not alter ghrelin, GLP-1 or insulin levels, and actually brings more distention of one end of the stomach, so it probably makes you feel more full rather than less full.

Don't worry, there are several other possible culprits. For one thing, most Chinese natives eat less meat as a part of the meal as compared to Westerners. Do low protein meals lead to decreases in satiety hormones or increases in hunger hormones? Probably not, a 2014 study showed that satiety hormone profiles were similar between good vegetarian diets and high meat diets.

How about low fat meals – less red meat and processed foods could also result in low fat Chinese meals.  Does eating low fat mean you’ll be hungrier sooner?

One problem with protein and/or fat hypotheses is that Chinese food as served in American restaurants today is not very Chinese. They use more meat, more fat, and more sauce than would be included in traditional Chinese meals. So I don’t think we can use them to explain CFH.

The idea of glycemic index is very hot right now. Originally developed to try and help diabetics better manage their blood sugar levels, weight loss gurus now lament that high glycemic index foods put the sugar into your blood very quickly and then cause you to crash to lower blood sugar levels sooner. This leads to overeating and weight gain. Eating low glycemic index foods (like vegetables and fruits) means that you don’t digest food as fast, and stay full longer.

Here are examples of high and low glycemic index foods and
their effects on blood sugar levels. Note that high GI foods don’t
crash your blood glucose at two hours, it’s just a little lower.
Might this be enough to increase appetite?
Some recent studies indicate low GI meals result in more CCK and didn’t increase ghrelin. This would suggest that Chinese foods high in vegetables would maintain satiety longer rather than make you hungry sooner. However, one 2008 study in overweight women showed that high GI foods led to more satiety hormones and less hunger. But again, American Chinese food uses lots of rice and sugary sauces, so it is has a much higher GI than traditional Chinese food.

Final answer – we don’t know why eating Chinese food results in being hungry again so soon. Science can be frustrating. Maybe it really is just a phrase that snuck into our language and gets repeated even though it’s not real. Sort of like the misconception that we only use 10% of our brain.

I suggest a rigorous, government-funded study. First to be determined is whether the satiety index of a Chinese food meal is significantly lower than that of an Italian, Mexican, or American meal. Step two would be to determine the effects of every Chinese food on the satiety and hunger hormones. If no food alters hormone levels markedly, then a study of pleasure center activation would be necessary. Any way you cut it, we’re going to need a lot of chopsticks, fortune cookies and small white cardboard boxes.

contributed by
Mark E. Lasbury MS, MSEd, PhD
As Many Exceptions As Rules

Neacsu M, Fyfe C, Horgan G, & Johnstone AM (2014). Appetite control and biomarkers of satiety with vegetarian (soy) and meat-based high-protein diets for weight loss in obese men: a randomized crossover trial. The American journal of clinical nutrition, 100 (2), 548-558 PMID: 24944057 

Geliebter A, Lee MI, Abdillahi M, & Jones J (2013). Satiety following intake of potatoes and other carbohydrate test meals. Annals of nutrition & metabolism, 62 (1), 37-43 PMID: 23221259
Boutry C, Matsumoto H, Airinei G, Benamouzig R, Tomé D, Blachier F, & Bos C (2011). Monosodium glutamate raises antral distension and plasma amino acid after a standard meal in humans. American journal of physiology. Gastrointestinal and liver physiology, 300 (1) PMID: 21030612

Friday, August 22, 2014

The Friday Five

Highlighting some of the coolest science news we’ve seen lately.

1. Remember the classic 80s B-movie, "Tremors", with Kevin Bacon? It looks like life is imitating “art” in the case of Eunice aphroditois (aka the Bobbit worm). Click here to watch this critter leap from out of the ground to gobble up an unsuspecting fish.
2. Cinnamon, Boris, and Sylvester. These were the names of the three cats that have helped scientists map the feline genome (no cats were harmed in these experiments!). 

3. An excellent video on the development of antibiotic resistance and evolution of scary “super bugs” like MRSA.

4. Also in antibiotic news, new studies indicate that some of these medications may have unintended consequences. In mice, low dose penicillin altered the normal gut bacteria, which had a long lasting effect on metabolism that predisposed them to obesity. But the research here is also in its “infancy”, so no one should withhold antibiotics to treat serious infections.

Additionally, another study has suggested that certain antibiotics given early in life may alter immunity in the long-term, again by impacting the normal bacteria inhabiting the gut.

5. While most people try to get rid of parasites, there is at least one man who invites them into his gut. Parasitologist Julius Lukes is using himself as a human guinea pig to convince others that parasites are not always bad and may actually have co-evolved to do good things for us. To prove they can be our friends, he’s infected himself with tapeworms. It will be interesting to see how this turns out “in the end”!      

Science quote of the week:

“The most exciting phrase to hear in science, the one that heralds the most discoveries, is not ‘Eureka!’ (I found it!) but ‘That's funny’..."  --Isaac Asimov

Contributed by:  Bill Sullivan
Follow Bill on Twitter: @wjsullivan

Tamazian, G., Simonov, S., Dobrynin, P., Makunin, A., Logachev, A., Komissarov, A., Shevchenko, A., Brukhin, V., Cherkasov, N., Svitin, A., Koepfli, K., Pontius, J., Driscoll, C., Blackistone, K., Barr, C., Goldman, D., Antunes, A., Quilez, J., Lorente-Galdos, B., Alkan, C., Marques-Bonet, T., Menotti-Raymond, M., David, V., Narfström, K., & O’Brien, S. (2014). Annotated features of domestic cat – Felis catus genome GigaScience, 3 (1) DOI: 10.1186/2047-217X-3-13

Cox, L., Yamanishi, S., Sohn, J., Alekseyenko, A., Leung, J., Cho, I., Kim, S., Li, H., Gao, Z., Mahana, D., Zárate Rodriguez, J., Rogers, A., Robine, N., Loke, P., & Blaser, M. (2014). Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences Cell, 158 (4), 705-721 DOI: 10.1016/j.cell.2014.05.052’’

Russell, S., Gold, M., Reynolds, L., Willing, B., Dimitriu, P., Thorson, L., Redpath, S., Perona-Wright, G., Blanchet, M., Mohn, W., Brett Finlay, B., & McNagny, K. (2014). Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2014.06.027

Wednesday, August 20, 2014

I hate you Charley, and the horse you rode in on

Sunday is the one chance I get to wake without an alarm, but the sweet dream of sleeping in often alludes me. Sunday at 4:00 am is when bombastic thunderstorms like to roll over my house.  Or one of the kids has the worst nightmare ever. Or some bird decides to whistle the most obnoxious symphony right outside my window. But even if I manage to dodge all these premature wake up calls, a Charley Horse rides into town looking for a fight.

We’ve all experienced this neuromuscular hell at one time or another. Mine come totally unprovoked. I’m just sleeping for crying out loud, and then I’m crying out loud - wide awake and trying to twist my leg off in order to stop the excruciating pain.

A Charley Horse basically feels like someone has twisted the muscles in your leg in the opposite direction of how they are supposed to run. The sensation is due to a spasm in those muscles, which usually subsides fairly quickly, although it feels like you could watch all the Harry Potter movies before the pain ends.

“Quick, Hermione, what is the spell that cures a Charley Horse?”

Known in some circles as “nocturnal leg cramps”, and in other circles as “just amputate my @&*$# leg!”, the Charley Horse is poorly understood. We don’t even know why we call it a Charley Horse. The reference first appears in the 1880s, believed to have its origins in baseball. According to this article, “the earliest known use of the term is from the Boston Globe, 17 July 1886:  Several years ago, says the Chicago Tribune, Joe Quest, now of the Athletics, gave the name of “Charley horse” to a peculiar contraction and hardening of the muscles and tendons of the thigh, to which baseball players are especially liable from the sudden starting and stopping in chasing balls, as well as the frequent slides in base running.”

But who is this Charley? Some say it was a ball player who owned a lame horse, but others say it was an actual lame horse, possibly the one that pulled the roller at the White Sox ballpark in Chicago at the time. But in 1907, according to World Wide Words, the American Dialect Society claimed that the phrase referred to the pitcher Charley Radbourne, nicknamed Old Hoss, who suffered leg cramps during a ball game. So it is possible that the original reference did not involve horses at all. 

“Charley Hoss, Charley Horse. Pretty close, especially in Boston.”
Obviously, people were getting these involuntary leg cramps long before we decided to hitch them to a Charley or a horse. The leading school of thought is that the muscles get all bent out of shape because of dehydration or an electrolyte imbalance. But before you go swimming in Gatorade, let’s review what a muscle is and why the minerals sodium, potassium, and calcium are important to function.

So a Charley Horse is basically a locked muscle contraction. For some reason, the muscles are “high strung” and won’t relax as quickly as they should. If you need another argument against intelligent design, the Charley Horse has legs.

Some have speculated that these satanic cramps can be prevented with dietary supplements. Magnesium is commonly touted as a solution to prevent Charley Horses but don’t giddy-up to your local GNC just yet. A Cochrane study performed in 2012 concluded that, “It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps.”
"They’ll put a cramp in your wallet and you’ll still get cramps in your legs."

How about stretching your legs before bed? While stretching doesn’t do any harm, it unfortunately is not likely to keep Charley Horses in the stable. There has also been a Cochrane analysis for the use of quinine to treat muscle cramps. While quinine does show modest benefit, the risks of serious side effects do not outweigh the possible benefit.

Your doctor is likely to tell you to stay hydrated. However, the idea that dehydration is linked to leg cramps simply doesn’t hold water when researchers put it to the test. Interestingly, what does provide relief is…pickle juice! Yes, just say it three times fast and the cramps will go away…no, wait, that’s Beetlejuice.

Testing this old home remedy, scientists artificially induced muscle cramping with electricity and then administered pickle juice or water. The pickle juice, but not the water, resolved the cramps faster. But since the cramp subsided faster than electrolytes from the pickle juice could possibly be replenished, the mechanism behind the pickle juice remains unknown. The authors of the study speculate, “Something in the acidic juice, perhaps even a specific molecule of some kind, may be lighting up specialized nervous-system receptors in the throat or stomach…which, in turn, send out nerve signals that somehow disrupt the reflex melee in the muscles.”

I guess for now, the Charley Horse will remain a physiological mystery. I’m sure I’ll have time to contemplate it next Sunday at 5:00 in the morning.

Contributed by:  Bill Sullivan
Follow Bill on Twitter @wjsullivan

Garrison SR, Allan GM, Sekhon RK, Musini VM, & Khan KM (2012). Magnesium for skeletal muscle cramps. The Cochrane database of systematic reviews, 9 PMID: 22972143

Coppin RJ, Wicke DM, & Little PS (2005). Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomised controlled trial. The British journal of general practice : the journal of the Royal College of General Practitioners, 55 (512), 186-91 PMID: 15808033

El-Tawil S, Al Musa T, Valli H, Lunn MP, El-Tawil T, & Weber M (2010). Quinine for muscle cramps. The Cochrane database of systematic reviews (12) PMID: 21154358

Miller KC, Mack GW, Knight KL, Hopkins JT, Draper DO, Fields PJ, & Hunter I (2010). Three percent hypohydration does not affect threshold frequency of electrically induced cramps. Medicine and science in sports and exercise, 42 (11), 2056-63 PMID: 20351595