Supplement Infographic

There's a lot of "woo" out there, especially when it comes to dietary supplements. Someone shared a great website with me that helps to cut through all the noise of company propaganda and get to the real issue of whether certain supplements do what they claim to do. This website at InformationIsBeautiful has done a great job at organizing the existing data for taking supplements and displaying it in an interactive chart so that you can see what works and what doesn't - and guess what? The majority of supplements out there don't make the cut.  Figures.

Take this screen shot from one of the latest editions of the chart:

The Y-axis represents whether or not the evidence is strong for the supplement in question. By simply scrolling the mouse over the circle you can see what the target effect is - for example, in the image above, the evidence is strong that garlic is good for lowering blood pressure.

The size of the circle around the supplement ID represents its popularity in Google's search engine. Green tea, folic acid, and vitamin D show the most hits, whereas peppermint oil, devil's claw, and melatonin show the fewest hits. The cool color of these circles represents strong evidence - the brown color indicates that supplement does not have much evidence for or against it, and continued surveillance is important.

Now let's look at what didn't make the cut:

Well, well, well - royal jelly, despite the many late night TV ads that have been put out, is probably one of the biggest flavors of snake oil out there. It bottoms out along with wheat grass, chamomile, papain, and certain anti-oxidants for having no effect.

The next time you see a commercial promoting the ingredient of some supplement for a desired effect, check this chart out to verify the claim - most likely the commercial is over-reaching its claims, and could even be distorting the data. If you want to read the science, just click on the circle the website directs you to peer-reviewed published articles that support the claim or refute it.

It's good to be in the know.

God Fucks Up: Science Saves the Day

For all of those out there who might still believe in a god, your god is a douchebag – unless, of course, you think that human life results from an embryo naturally developing from the fusion of a sperm and an egg (which is susceptible to teratogens, natural genetic aberrations, environmental influence, etc.).  Otherwise, some deity just gave a pre-born baby a giant deadly tumor that weighs more than the baby itself (pictures below).  Oh, and if you think there's a god behind the natural events leading to human life, I’m sure you also think a god is responsible for creating the universe.  If so, your god is also responsible for everything in it, including the natural phenomena that lead to deadly cancers.  Try as he/she/it might, even divine corruption did not stop doctors from blocking the evil masterwork of giving a baby in gestation a giant tumor.

The fascinating story was recently published in the Journal of Pediatric Surgery entitled: “Preoperative embolization of giant sacrococcygeal teratoma in a premature newborn”.  In other words, “We [doctors] cured a prematurely born baby of a deadly tumor that weighs more than the baby itself.”  This was no small feat – your god has had … well … an eternity to perfect the art of giving living things cancer – scientists and doctors have only had a hundred years or so to really fight back.  Great news: we’re getting better at beating god’s evil plans!  In fact, this particular method of foiling god’s cancer plans has only been used once before.

At about 20 weeks of pregnancy the large tumor was identified as a sacrococcygeal teratoma, or SCT.  Teratomas are special tumors that can also be very dangerous – they originate from your germ cells (the cells that make sperm or egg depending on if you’re a male or a female).  SCTs are one of the most common forms of teratomas because they arise in the pelvic region, right where germ cells can end up if they get off track from your gonads.  In this particular case, the mother was immediately give corticosteroid treatment to ease her immune system and protect the baby.  This particular tumor was immature meaning that it had very aggressive and potentially malignant cells inside it.  After close monitoring of the mother and unborn child, the mother suddenly entered labor at 30 weeks and the doctors had to perform a C-section.  This is what they found attached to the baby after delivering her:

The combined weight of baby and tumor was 3.43 kg.  The tumor itself weighed (1.86 kg) more than the baby (1.57 kg)!  Unfortunately these kinds of tumors are very dangerous to cut off (ressect) because of the huge risk of bleeding.  The bigger the tumor, the bigger the arteries carrying blood, the bigger the risk of the baby bleeding to death before the doctors can save her.  Fortunately, the doctors have science on their side.  After taking a picture called an arteriogram, the doctors were able to see the main artery that was sourcing the blood to the tumor (see the arrow):

 Normally doctors try to keep your blood stream clean of cholesterol – otherwise you might get a clot that will stop the blood flow and kill you.  In this case, the doctors reckoned that they could induce an artificial clot (called an embolism) right at the site of the artery branching off to the tumor to block the blood flow and attempt to choke it off from oxygen and food – this way, when they ressect the tumor there would be less risk of bleeding.  So, they used a commercial product called Gelitaspon (small gelatin sponges) and injected some in the artery leading into the tumor.  You can see here that this successfully reduced the blood flow to the teratoma:

At this point the doctors ressected the tumor and the bleeding was minimal.  Unfortunately there was a lot of cell death from the tumor that had still managed to circulate in the baby’s bloodstream (hemolysis) which caused major problems, culminating in a full on cardiac arrest (heart attack).  The baby’s heart stopped for a full 6 minutes.  SIX MINUTES!  I guess god really didn’t want this baby to be born.

Fortunately, doctors provided injections of gluconate, insulin, adrenalin, hydrocortisone, and other science-y drugs that saved the baby’s life.  After 6.5 weeks the baby was allowed to leave the hospital and has been receiving monthly checkups every since.  Despite a solid effort by your god, the baby survived.

If you’re someone who likes to give a god credit for things like the sunrise, the ocean’s tides, the formation of the grand canyon, and/or the “miracle” of human life, then it’s high time you also start giving your god credit for the viruses, bacteria, and cancers that are so good at destroying human beings.  Let’s face it – if you think a god is behind the scenes of nature, then to human beings, your god is a douchebag.

Moving Targets within a Cell

Anyone who has had an introductory molecular biology class knows that the genetic information for almost all living things (this idea gets trickier if you count viruses as living things) is stored in the form of DNA, or deoxyribonucleic acid. DNA is an elegantly simple, stable molecule that is a candidate for being the longest naturally occurring molecule on the planet (in your human cells, a single molecule of DNA would be two meters long if stretched from end to end – and that’s just from one cell!). From your introductory biology class you should also remember that, while DNA stores the genetic information, this information has to be turned into protein (the stuff that actually IS you) via an intermediate called RNA, or ribonucleic acid.

That one little “deoxy” difference between DNA and RNA makes RNA a very dynamic (and frequently unstable) molecule. In chemical terms, “deoxy” is referring to the lack of an Oxygen atom (or hydroxyl group) in DNA that is present on RNA:

Oxygen, if you don’t already know from principles of how a fire burns, is a very reactive species in the chemical world, so it makes sense that the presence of an extra oxygen atom in the RNA molecule makes it more unstable than DNA. However, the dynamic nature of RNA makes it really handy for all kinds of other chemical reactions and cellular processes – another way to say “unstable” is to just say “reactive”; and in your cells, millions of chemical reactions take place all the time, so a reactive RNA is really useful. In fact, it turns out that your cells can regulate on a finer scale whether a gene is turned on or off at the RNA level than at the DNA level.

Think about it: if you want to turn a gene on (genes are made of DNA), you need to get all the molecules situated just right over the gene so that it can make copies in its intermediate form of a particular kind of RNA called messenger RNA, or mRNA. Those mRNA copies can then go out of the nucleus into the rest of the cell and be turned into protein. Of course, you only have two copies of a gene in your cell, a pitifully small number. How can you make billions of copies of a protein from only two copies of DNA? Well, your cell makes thousands of mRNA copies of the DNA gene. Those thousands of copies of mRNA go out into the cell and are used by other molecules to make protein – usually, one mRNA copy is read over and over again to make lots of protein, and that’s how you get millions of copies of a single protein in a short amount of time.

When a cell is done making and using this protein, it can go down to the DNA to “shut off” the gene by removing all those molecules that are making mRNA copies, which will in turn keep any new protein from being made. That is, as long as the mRNA copies that are already present simply go away once the DNA gene stops making them.

But what exactly happens to an mRNA copy after the DNA gene is turned off? Does it just degrade and disappear? Can it linger around? Can it be “turned on” and “turned off” like a DNA gene can? These are all questions that people who work on RNA biology have been asking for quite some time, and the answers can be pretty amazing and pretty complex.

While other classic research has shown that mRNA copies can hang around and be turned “on” or “off” regardless of what’s happening to the DNA gene, a study published in 2007 showed some pretty cool results demonstrating that RNA copies can be trafficked around inside a cell by riding along one of the biggest structural proteins inside a cell: microtubules.

Michael Blower at Harvard University, in collaboration with Karsten Weis and Rebecca Heald at UC Berkeley showed unambiguously that mRNA copies can bind to microtubules and play an important role in localizing their protein products to a specific site within the cell. As you can imagine, trying to get enough molecules to do experiments can be hard sometimes, especially if you have to do all your experiments from a single cell. However, scientists have clever ways to amplify material, and they have a habit of studying animal models that have REALLY big cells to make this easier. This is where females from Xenopus laevis, or frog, come into the picture. Xenopus females lay incredibly large eggs (an order of magnitude bigger than human eggs) and in very large numbers (400-500 at a time!). Blower and colleagues used these massive cells to extract and purify allll the microtubules (MTs) from the rest of the cell – what they found is that there are mRNA copies stuck to the MTs!

This graph is showing you all of the mRNA copies in the Xenopus eggs and whether they are bound to MTs or not. The X-axis is showing you “enrichment on MTs” and the higher the number, the more it’s enriched. The Y-axis is showing how many mRNA copies are enriched at that amount. For example, there are 140-160 mRNA copies that are approximately -1.4 Log2 enriched, and only 5-10 mRNA copies that are about 1.3 Log2 enriched. Notice that a lot of the transcripts are not enriched; in fact, they’re in the negative numbers indicating that they aren’t found on MTs but elsewhere in the cell (makes sense). However, a select few mRNA copies are actually enriched. Fortunately, the experiment that gave them this pretty graph also gave them the identities of each and every one of those mRNA copies.

So they did the next logical thing: if one experiment suggests that certain mRNA copies are stuck on MTs, then this should be visible in the cell. They decided to check it out using a microscope by labeling an mRNA and MTs to see if they look stuck on each other (the scientific word for “stuck on each other” is “overlap”). Don’t you worry about how they labeled it – that’ll be an entry for another blog post some time.

The red color indicates MTs and the green color indicates potential mRNA copies that should overlap (blue represents the DNA, but just ignore that for now). Notice that the left two panels show green mRNA copies that actually do overlap in the same region as the red MTs – this is exciting and confirms their finding. On the right you see a negative control – or an mRNA copy (called net1) that should NOT bind MTs, and indeed you don’t see any green staining, do you?

This is really cool, but the people who gave these researchers money to do research are … well, they’re taxpayers! And taxpayer money (funneled through the National Institutes of Health, or NIH) means that there’s usually a pretty strong interest in human experiments, not frog experiments. So the next question was, “If this happens in frogs, can it happen in humans?” And that’s exactly what they checked – so they took some human cells that grow in culture (no human eggs or anything like that, just human body cells), purified allllll the MTs away from the other stuff, and did the same initial experiment:

Notice again that a few mRNA copies are enriched on MTs, but most are not. This is a pretty cool idea: the same thing that can happen in frog eggs is going on in human cells too! But why would mRNA copies want to be on MTs? If mRNA copies are located on MTs, does that mean protein is made on the MTs as well? The process of reading mRNAs and making protein from them is called translation. So the scientists in this paper performed an experiment to test whether translation (the process of making protein from mRNA copies) is occurring on MTs. A clever system was adopted from previous work devising a method of labeling sites of active translation with a derivative of the antibiotic puromycin. Puromycin kills cells by getting lodged into the molecular machinery that turns mRNA copies into protein. So scientists made a version of puromycin that is tagged with a fluorescent molecule to see under a microscope. By injecting small amounts of this glowing puromycin into cells, it lodged itself into molecules called ribosomes, and labeled active sites of translation (such small amounts were injected that cell death was not a concern):

It worked! And it appears that translation is occurring on MTs. Notice the green puromycin in the left panel, which labels active translation, overlaps with the red color labeling the microtubules. You'll also note that it seems to be concentrated green at the tips of the red staining. That area is called the spindle pole, and the right panel shows a different green marker, ribosomes. Ribosomes are the molecular machinery that promote translation of mRNA copies into protein. So translation machinery is located on the MTs and at the spindle poles, and we know that active translation is occurring on MTs because the puromycin stains it too!

This is a pretty clever trick to answer their question, and they also proceeded to show that the same phenomenon occurs on MTs in meiosis as well as mitosis (remember that meiosis is cell division of the sex cells in your body, but mitosis is cell division of the rest of the cells in your body - the focus is on cell division because that's when lots of MTs organize to form really clear structures that you can look at). The last question they attempted to address was, “Is the process of translation necessary to move the mRNA copies to the MTs?” This is more important of a question to answer than you realize, but it is difficult to know what is responsible for moving mRNAs around a cell.

One hypothesis is that the translation machinery moves mRNA copies to MTs, so that’s one of the easier questions to answer. This time, the experiment required a bigger dose of purmocyin to stop the process of translation altogether. If translation is stopped altogether, then the mRNA copies may or may not be located on the MTs. The results are below:

The microtubules are in red and the mRNAs are in green. The top row is normal cells and the bottom row shows cells treated with the translation inhibitor puromycin – notice that the green mRNA copies still localize to the MTs even when translation is inhibited with puromycin in the bottom row.

These experiments, among others, make this a great paper. However, there are many questions that are left unanswered. Why are some mRNA copies localized to MTs but not others? What molecules and processes are responsible for bringing the mRNA copies to the MTs? If the mRNA copies are not allowed to localize to the MTs, will something bad happen? You can easily see how the experiments for the next possible paper are shaping up.

If you found these results interesting, you might also like this incredible video made at Harvard, animating the life of a cell. In it, you’ll see one depiction of how scientists currently think mRNA copies and other cargos are moved along microtubules (to some pretty awesome music no less).

Stay tuned for more science next week!

Let's get THIS in clinical trials

I heard someone snickering in the lab bay next to mine today. I asked them to share with me the source of their joy. It's the title of a research article from a recent publication of the journal PLoS ONE (Public Library of Science):


Here's the summary for those of you who don't have access to the journal (but you should because it's PLoS):

Abstract
Oral sex is widely used in human foreplay, but rarely documented in other animals. Fellatio has been recorded in bonobos Pan paniscus, but even then functions largely as play behaviour among juvenile males. The short-nosed fruit bat Cynopterus sphinx exhibits resource defence polygyny and one sexually active male often roosts with groups of females in tents made from leaves. Female bats often lick their mate's penis during dorsoventral copulation. The female lowers her head to lick the shaft or the base of the male's penis but does not lick the glans penis which has already penetrated the vagina. Males never withdrew their penis when it was licked by the mating partner. A positive relationship exists between the length of time that the female licked the male's penis during copulation and the duration of copulation. Furthermore, mating pairs spent significantly more time in copulation if the female licked her mate's penis than if fellatio was absent. Males also show postcopulatory genital grooming after intromission. At present, we do not know why genital licking occurs, and we present four non-mutually exclusive hypotheses that may explain the function of fellatio in C. sphinx.

And they didn't just quantify the relationship; they included a HAND-DRAWN PICTURE of the act in process. The artist? Mei Wang, who didn't even make it as an author ... weird. Seems like a worthy contribution. I make powerpoints of mice having sex all the time.


And what peer-reviewed article about fellatio would be complete without a video ... and porn music to boot?




The only downside here is that even though we're talking about mammals, the overall duration of fellatio was pretty short. The authors write, "The average duration of penis licking was 19.14±3.45 s, representing about 8.7% of the average duration of copulation (220.29±26.19 s (N = 14))." But hey, almost 10% of total copulation was spent giving head ... that seems cool. Another interesting point is that the female only licks the shaft because the glans penis is already inserted in the vagina. It's an interesting trick that I don't think many human females can try.

The authors speculate on four possible explanations for the function of fellatio in C. sphinx:

Number 1: Lubrication. That makes sense - stimulation for the male and easier thrusting. It's a win-win.

Number 2: Mate-guarding. Apparently the male hangs around longer with longer copulation, and I suppose the females want that? I'm not so sure about this one.

Number 3: Prevention of STDs. Bacteriocidal effects of saliva can help a dude out ... and a girl for that matter. I think this is a great idea.

Number 4: Detection of chemical cues for mate choice. Eh. I mean, it'd be cool if this were true, but they didn't have an example of any female licking and then stopping coitus. Is this just an act of affirmation that she's picked the right mate? I think this is the weakest hypothesis.

Favorite part is at the end, "The behaviour presumably favours the donor, although it may also benefit both partners especially if fertilization success is increased. It is conceivable that the female manipulates the male by increasing sexual stimulation, so that she ultimately benefits."

Bottom line people: Have more oral sex. It's evolutionarily good for you.

Huge teratoma of the WHAT?!

Just published in the Journal of Cranio-Maxillofacial Surgery is an article entitled "Huge teratoma of the face". That's right - the face.

It looks to be about as painful as it sounds too. Below and on the left is a picture of the 4-month old infant with the rapidly growing tumor (right before surgery); on the right is a picture of the girl at seven years of age (way after the surgery).

As the authors state:

The case we report was entirely benign, did not relate to vital structures and had no intracranial extension.

This made it possible to surgically remove the tumor without there being permanent damage to any vital function. As you can see from the images below, even the bones of the face were distorted by the growing mass.


A teratoma is the kind of tumor that I study in mice. We have a mouse model for testicular teratomas. These mice have a mutation in a particular gene that renders the protein made from that gene to not work. This causes misregulation of the germ cells (the cells that colonize the gonad and eventually give rise to sperm in the testis). In this particular mouse, the misregulation leads to a teratoma.

Teraomas have long fascinated biologists by their ability to grow incredibly fast and show amazing signs of organization and differentiation. They are thought to arise from very powerful, or pluripotent, cells such as germ cells. In this case, instead of colonizing the gonad, a germ cells got off course and wound up in the head and neck region. Normally if this kind of misguidance happens the cell can't survive and dies off. But sometimes (rarely) it doesn't die off, and instead begins to grow and develop outside of the proper environment. Overall, teratoma formation is a relatively rare sort of tumor, especially in the face.

Nevertheless, this demonstrates the power of the cells that make up your germline and give rise to your gametes. Remember that gametes (spermatocytes and oocytes) combine to give rise to the next generation. That power is harnessed very carefully by nature, and sometimes things go wrong. This study is a case in point.

Cellular Manipulations ... Stem Cells on the Rise

Just last week in the peer-reviewed journal Science, a report was published detailing how to generate induced pluripotent stem cells (or iPS cells) through genetic manipulation without the use of viral vectors. This work was submitted by Keisuke Okita, Masato Nakagawa, Hong Hyenjong, and Shinya Yamanaka.

Dr. Yamanka and colleagues previously published research detailing their work creating iPS cells using retroviral and lentiviral vectors that randomly incorporate into the genome of the host cell. These incorporated genetic components used only three genes: Oct4, Sox2, and Klf4. The resulting iPS cells could differentiation into any cell type.

Though promising, clinical progress would be limited due to safety concerns using retroviral/lentiviral infection - it turns out this poses a seroius risk of activating or inactivating important host genes that could ultimately lead to cancer or other disastrous consequences.

Using this new plamist transfection reported this month, that risk is averted - though the efficiency of manipulation is actually lower. The successful cells could still be differentiated into progeny of all three germ layers, indicating the continued power in iPS cells derived using this newer method.

While efficiency issues still need to be worked out, this is a huge step forward and could soon be translated into the clinic with a lot more hard work.

The XX --- XY divide ... evidence from Turner's patients.

I thought it would be fun to enter a science post ... and not just any science post, but something really cool and taken from about a decade ago. I work in a lab that focuses on mammalian sex determination, and there are many interesting debates that are tackled on a day-to-day basis. My boss brought this study to my attention earlier this month, and it was concerning research published in 1997.

David Skuse is very creative and wanted to find a way to see if there are differences in sex chromosomes depending on if we inherit them from mom or dad. In humans, two X chromosomes (XX) leads to female development, and an X and Y chromosome (XY) lead to male development. As such, when your parents used their gametes to make you, your mom HAD to pass on an X chromosome to you. If you are female, then dad happened to give you his X; alternatively, if you are male, then dad happened to give you his Y.

Well sometimes things don't go as planned, and instead of passing one of these on to you, a parent's gamete fails to deliver with any sex chromsome at all. Now, if you only receive a Y chromsome, you can't develop at all - the embryo can't survive. But if you only receive one X chromosome, you'll grow up just fine, though with a few minor problems. This scenario (45,X) is referred to as Turner's syndrome. These individuals, while only having one X chromsome, will develop physically as females. But interestingly, the single X chromosome could come from mom OR dad.

David Skuse saw this special group of individuals as a fantastic opportunity to explore some questions we have about human (and sexually dimorphic) behavior. In general, we think of girls as having better social cognitive function than boys. But could there be a genetic basis for this? The Y chromosome is very tiny in comparison to the X, so there are actually many genes that only exist on the X (which is important because you ALWAYS get two copies of every gene, one from mom and one from dad, unless you are a boy and only have one X). To keep things fairly at an equilibrium, girls actually INACTIVATE one of their X chromosomes so that they only use one, just like the boys - though this inactivation process is random. In the end, ALL boys use the X that their mom gave them, but girls use either the X from the mom or from the dad. This is where it gets interesting.

David Skuse hypothesized that maybe these X chromosomes are not the same - maybe they are partly responsible for different behaviors that we associate with the different sexes. He looked at Turner's syndrome patients and saw that some got their X from mom, while others got theirs from dad. He did a basic and thorough study to determine the social cognitive skills, comparing patients who got their X from mom directly to those who got their X from dad. His results are very interesting!


Subjects who received their X chromsome from the mom, scored much higher for social-cognitive DISFUNCTION! Individuals receiving their X chromsome from dad were much better adjusted and had better social-cognitive ratings. When compared to normal individuals, normaly XX girls have better social-cognitive skills than normal XY boys. This supports the notion that something on the X chromosome influences this behavior - XY boys have to get their X from the mom, and they do perform poorly, like the Turner's patients receiving the X from the mom. Alternatively, XX girls can use the X from either mom or dad, and they do much better with social-cognictive skills, like the Turner's patients receiveing the X from the dad.

This simple, yet elegant, study revealed the presence of an X-linked imprinted locus that affects social-cognitive skills in human sexually dimorphic behavior and supported the hypothesis of a genetic basis for this complex phenotype. Additionally, to quote the last sentence of the abstract, "If expressed only from the X chromosome of paternal origin, the existence of this locus could explain why 46,XY males (whose single X chromosome is maternal) are more vulnerable to developmental disorders of language and social cognition, such as autism, than are 46,XX females."

So remember, ladies - you have your fathers to thank (in part) for your superior social-cognitive skills. And guys, you can at least have the satisfaction of knowing that you'll be helping your daughter out, should you indeed 'decide' to pass on your X chromosome.