In helping my wife with migrating her site to our host, I accidentally ruined all the posts on mine! That’s a lot of fun. Most of them are back now, so we can keep on rolling! The newest ones got lost permanently, though…
My wife and I were watching Lincoln a few weeks ago. I thought it was a pretty good movie, overall. We have doubts about some of the finer details with regard to people, but it was an interesting look into what life was like in the mid-19th century.
I have to say, for my sake, that I liked Tommy Lee Jones’s portrayal of Thaddeus Stevens more than I liked Daniel Day Lewis as Lincoln. Crucify me for that one! I just liked the character so much more, I think. He was acerbic, hilarious, and a joy to watch. And his speech arguing in favor of the amendment was a freaking awesome turnabout; I would watch the whole movie again just to see it!
During one of the House scenes, I noticed this line, almost a throwaway:
THADDEUS STEVENS - when will Mr. Wood conclude his interminable gabble? Some of us breathe oxygen, and we find the mephitic fumes of his oratory a lethal challenge to our pleural capacities.
Funny, and very pointed. But I heard that and wondered about the oxygen line. Would the real Stevens have known about this fact? It’s obvious to us, but you have to remember that oxygen had only been discovered about 60 years prior. That is, we FIRST learned about its existence not very long before the events of this movie.
It’s no mystery how oxygen was discovered. In fact, it’s one of the more famous snafus the field of chemistry ever committed. You had the false notion that phlogiston was a substance that left a material as it was burned, which is quite the opposite of what actually happens (oxygen enters the material). You had the man who named the element, Antoine Lavoisier, misattributing the element as a key constituent in ALL acids.
But the biological phenomenon of respiration, when did we know about that? We’re talking about 1865 here. The key components of cellular respiration, breaking down sugars and forming ATP, were not worked out until a good deal later. The key pieces were worked out in the 20th century, so it would seem that Thaddeus Stevens should have no knowledge of this phenomenon.
Step back, though. That’s respiration on the cellular level. When did we understand respiration on the organism level? This is pretty obvious, and so it was characterized much earlier. We figured out the nature of the lungs a really long time ago. Leonardo da Vinci was writing about them in the 15th century, ”The substance of the lung is dilatable and extensible like the tinder made from a fungus. But it is spongy and if you press it, it yields to the force which compresses it, and if the force is removed, it increases again to its original size.”1
It should come as no surprise, though, that our initial understanding of the lungs was laughably poor. The act of breathing was thought to bring fresh, cool air to reduce the temperature of the heart. It didn’t take that long, however, to figure out that air was a vital component to life.
Here’s the key to answering the question, in my mind. In the late 1700s, oxygen was discovered separately by several chemists. It was shortly thereafter that it could be shown that breathing animals would die if this gas was removed from the atmosphere in which they breathed. So we’re in a time window when Thaddeus Stevens, who attended Dartmouth and graduated in 1833, would have been near the cutting edge of this chemistry. In essence, it’s hard to know that the real Thaddeus Stevens knew about oxygen and the fact that we breathe this gas. He obtained an Ivy League education, though, so it seems like no big stretch!
When I was just a chemistry student, I got it into my head that the very notion of a poison just didn’t make any sense. At all. My thought process went something like this: you have this disastrous substance, some nasty poison. Why wouldn’t our bodies evolve to simply ignore it? If you ingest some toxic substance, why can’t we just dump it out of the other end? It’s like your body is holding a bomb and chooses to do something with it instead of just letting it go.
I never really got that question answered. Now I feel pretty dumb for ever wondering, quite frankly. The answer is really right in front of you when you have an idea of how poison works, in general. REEEEALLY in general.
So How Does a Poison Work?
We think of toxic substances as foreign materials that need to be dealt with by the body. Basically, we’re just a vessel for shutting down outside stuff. It’s really not the correct idea, though. We exist in a world that is mostly not us. It’s kind of difficult to separate that when your whole purpose in life is to stay alive and reproduce. Everything not you is a potential threat.
Poison is not really a threat to us, per se. It just exists, and it happens to disrupt body functions in us. Sometimes this is to a better end for the maker of the poison, as is the case of spiders and snakes and other venomous creatures. Other times, it’s more incidental. Alcohol is a poison for us, but yeast don’t make it to defend themselves from us. It’s a waste product.
Poison, The Deadly Mime
So what makes poison work against us? Much of the time they mimic molecules that the body uses normally. For example, take tetrodotoxin, the agent of choice made by the blowfish.
I promise not to be gentle!
Tetrodotoxin, besides having a completely awesome name, is a potent molecule synthesized by the blowfish. Improper preparation of this meal can result in a serious case of death, so it’s best to be careful. What does tetrodotoxin do? It binds channels that your neurons require in order to fire off properly. Tetrodotoxin binds these can basically shuts them down, preventing signals from being propagated. By being able to bind this particular site, tetrodotoxin is kind of in the wrong place at the wrong time. If you like breathing, that is.
Speaking of breathing, how about hemoglobin? You know, that molecule in your blood that helps you absorb oxygen? Shutting that down can have some bad effects for the body. One of the most famous and effective poisons works by doing that, exactly! The hemoglobin molecule works primarily by housing an iron at the center of a protein. The iron helps to bind oxygen and other gases for carriage. Cyanide can work against this process by sticking like super glue to the iron. It’s like a much more potent form of carbon monoxide (you’ll notice the similarities in their chemical formulas, CO and CN; it’s not a coincidence that they’re both toxic).
So there’s a lot of poisonous stuff out there. It’s really quite fun to learn about how these agents act against the body. So now you know, and knowing helps you avoid inhaling hydrogen cyanide, in case you ever got curious about it.
Antibodies as Tools
So you may remember learning in school about how the body’s immune system works. You may also remember the key role of antibodies, those guys that go around and trap the disease. Have you ever wondered how they work? Did you know that in biomedical research they are the cornerstone of almost every paper out there?
Biomedical scientists have managed to usurp nature in a lot of ways. The production of antibodies to proteins of OUR interest is one of the key findings of the 20th century.
What are antibodies, exactly?
So we hear about these little beasts in all kinds of contexts. What are they, really? A key function of the immune system is the detection and removal of foreign organisms. Since bacteria and fungi and other pathogens do not have the same biology as us, our body is able to differentiate them. We have evolved to make all kinds of receptors to send off an alarm to the immune system that something is wrong. Then cells called macrophages come and gobble up the offending invade. It chews up its proteins and sticks them on the outside as a “presentation” to T cells, which can go on to activate production of antibodies by B cells designed against what it saw.
It’s kind of like the macrophage is a scout against an unknown enemy, and the T cell is the general who tells the B cell soldier scientists how to beat up the threat. The initial weapon of choice? Antibodies. Once production gets into full swing, the antibodies float around the bloodstream and attach to the invaders, triggering recruitment of killer cells that come in and wipe out the infection.
How do we use antibodies in research?
In the 1970s, we discovered a certain kind of myeloma derived from B cells. A myeloma is a tumor that is formed from plasma cells. These specific B cell myelomas were still able to produce antibodies, but they never stopped dividing (being cancer, after all). So basically they could be used as antibody factories. With the discovery of hybridoma formation, we were able to fuse the myeloma cell’s genes with a B cell exposed to the protein of interest. In this way, we could tailor production of antibodies however we liked, to whatever protein we desired.
How is this useful?
If you study proteins, you have a pretty significant challenge when it comes to just looking for them. They may be large molecules, but they’re still too small to look at with most of the tools at our disposal. Antibodies give us a way to ask the question, “Is my protein here?” This is because antibodies can distinguish a single protein out of a huge mixture (if it’s a high-quality, good antibody, of course!).
I’ll be taking a closer look at specific things we do with antibodies, but let’s end this post with something awesome. A cool real-world application of antibodies is the pregnancy test. They all basically work the same way. In the weeks following conception, a woman’s body begins manufacturing the protein human chorionic gonadotrophin (hCG). The test itself is a strip coated with antibodies that specifically look for hCG and attach to it. If hCG is found in the urine, the flow carries antibodies through chambers in the pregnancy test, reaching a certain point that results in the release of a dye in a specific pattern. Hence, you often seen the + sign for positive. If the hCG is not present in high-enough amounts, you don’t get one of the lines, giving you the negative result. This also explains why the “positive” test result ALWAYS adds more information, like an extra line, and never takes it away.
But it’s all thanks to antibodies that this technology works. Later, we’ll get into how scientists use these molecules! Hint: some of it will include some concepts already covered on Really Cool Things!
Anorexia Nervosa has this stigma associated with it, at least in my part of the world. We’re all about personal responsibility (especially when it’s someone else who needs to be personally responsible!). So a mental disorder like anorexia kind of gets passed off as an “all in your head” kind of phenomenon. New research published in the journal PLoS One, however, fuel the legitimacy of this disorder.
What is Anorexia?
For those who don’t know, anorexia is one of many recognized eating disorders. Based on body image the man or woman who is affected simply stops eating. The diet restriction is taken to an extreme, and the afflicted person tends to have a way-too-harsh fear of gaining any weight at all. It can be severely harmful to a person. Caloric intake can be as low as 600-800 calories per day, which is well below what you should eat. Anorexia can be associated with severe malnutrition symptoms and psychological disorders. It affects as many as 8 in 100,000 people per year.1
So What’s New?
There has been a good amount of research done on anorexia. Scientists are quite interested in what makes this disease tick, as you can imagine. Your first assumption upon meeting somebody with anorexia may be a knee-jerk. “You’re normal!” you may think. “Just eat something. Here’s a hamburger! It’s all in your head!”
For someone without the disease, this is easy to do. After all, most research has focused on the impact of body image with the disease. A man or a woman irrationally fears weight gain, so he or she voluntarily self starves. This sounds like something you should be able to snap out of. New research suggests it’s not that simple, though.2 It turns out that patients with anorexia also have an innate skewed sense of body mass.
How Was That Determined?
The researchers in this study used what they called an aperture, basically a door, to gauge how anorexic women reacted to doorways of different sizes. As you know, the body kind of “knows” when the space is getting to narrow to fit, even if you can’t see your shoulders. You rotate in order to avoid the obstacle once it starts getting too narrow, as your body sees it. Normal women in the study started to rotate to avoid the aperture once it was around 25% wider than their shoulders. If the average shoulder width of a woman is 14 inches,3 that means she will start to rotate if the door is 17-18 inches wide.
On the other hand, women with anorexia started rotating their shoulders when the doorway was only 40% wider than shoulder width. Taking the same average of 14 inches, these women’s bodies perceive themselves as too wide too fit in the door once it’s about 20 inches wide.
The interesting part of these results is that the women in the study didn’t really know what was going on. The rotation was basically a reflex, not part of how she viewed her own body. It suggests that unconscious reactions to stimuli can be affected by anorexia nervosa. This provides more evidence that anorexia is a problem more ingrained. So if you still think anorexics should just get over it, think again!
1 Hoek HW. Incidence, prevalence and mortality of anorexia nervosa and other eating disorders. Curr Opin Psychiatry. 2006 Jul;19(4):389-94.
2 Keizer A, Smeets MAM, Dijkerman HC, Uzunbajakau SA, van Elburg A, et al. (2013) Too Fat to Fit through the Door: First Evidence for Disturbed Body-Scaled Action in Anorexia Nervosa during Locomotion. PLoS ONE 8(5)
My wife caught a news story the other day related to obesity and pregnant women. As it turns out, obesity can cause the methylation status of certain kinds of genes to change, as published in an article from the Proceeds of the National Academy of Science (PNAS).1 I thought this was a very interesting article! I went to seek it out so I could read it, as PNAS is a very well-respected journal.
I did manage to find it after being distracted by this one: Penis size interacts with body shape and height to influence male attractiveness. That’s a much less-appropriate point of discussion, though.
What’s the deal with obesity in pregnant women?
So several years ago, a study was published demonstrating a link between women who underwent bariatric procedures and the rate of obesity in their offspring.2 Basically, that rate dropped dramatically (by 52%!) when compared to the children of obese mothers who did not experience dramatic weight loss. Obesity rates were dropped all the way through adolescence.
How Gastric Bypass Works, clipping the stomach and rerouting food straight to the intestine to fight obesityHow Gastric Bypass Works, clipping the stomach and rerouting food straight to the intestine
That was 2006; what’s the news now?
The study that was previously published gave us an initial observation. The next question should be obvious: why? How could a bypass procedure (basically, forced malnutrition) change the baby’s genes? First, it should be made clear that the mothers did not undergo the surgery while pregnant. The comparisons made were for mothers who first had a child while obese, had the surgery, and then got pregnant again.
Changes to the baby as a result of the mother’s weight would not really be genetic, since the siblings birthed before the surgery still had a greater risk for obesity. This suggested to the researchers that a different, less fundamental change was occurring. Environmental factors can’t really change your genes much (except for damage, of course, like by ultraviolet radiation), so an obese mother won’t change your genome.
As it turns out, the baby may be inheriting epigenetic changes. Specifically, the baby’s genes are undergoing changes in what is called methylation. What is that? Methylation is the addition of a methyl group to DNA, which can alter how it is expressed. We’ve only recently started to gain an appreciation for these types of changes, and the most interesting thing about them is that they can be gained from the environment, AND they can be inherited from your parents!
As it turns out, there were clear changes in the methylation of certain genes involved in metabolism. As is often the case with this type of research, the group found more than 5000 different events, so they didn’t get into too many specifics on what genes were regulated this way. I’m sure this will be the subject of future research, trying to tease out exactly what changes lead to increased obesity risk.
At any rate, it’s incredibly interesting! Thinking of getting pregnant? It seems it is best to try and reach a normal weight firs
1 Frédéric Guénard, Yves Deshaies, Katherine Cianflone, John G. Kral, Picard Marceau, and Marie-Claude Vohl. Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery. PNAS 2013 ; published ahead of print May 28, 2013, doi:10.1073/pnas.1216959110
2 Kral JG, et al. (2006) Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics 118:e1644–e1649
3 Richards EJ. Inherited epigenetic variation–revisiting soft inheritance. Nat Rev Genet. 2006 May;7(5):395-401.
What other fluorescent stuff are we going to see?
The world is really wide open when it comes to fluorescence. Scientists have spent a lot of time improving on how we do things. I want to talk to you today about other fluorescent dye molecules. They have more advanced applications and are actually quite cutting edge!
Why do we need other fluorescent dyes?
There are some pretty big problems associated with using fluorescent molecules for research. First, you often need to tag the dye to something else so you can watch it. That’s usually not too big a deal; the chemistry is well worked out. The biggest issue you run into, though, is a concept called photobleaching. This is where the fluorescent molecule gets excited for a while, but it eventually peters out. Basically, the molecule loses its fluorescent properties.
So working around photobleaching is something we strive to do to improve our molecules. Fluorescein photobleached very easily; Alexa Fluor dyes were much improved, but you still need to watch with them. What else can be done? Where does the future lay?
Enter the Quantum Dot
The solution, it would appear, is the move to the quantum dot as a fluorescent agent. That’s a really cool name, isn’t it? Quantum dots…but what are they?
Quantum dots are actually tiny semiconductors, similar in certain properties to computer chips. Beyond that, you get into solid-state physics. Well beyond my reach to explain. There are a few key takeaways for quantum dots we need to know.
- They are nanomolecules.
- Their fluorescent color is based on their size, not necessarily what they’re made of.
- They are massively brighter and more stable than other known dyes.
The nanomolecule part is just interesting; nanotechnology is this rapidly-growing field, and now you know that quantum dots are part of it! The more important attributes are found in the customizability and stability. By simply manufacturing them slightly differently, the quantum dots will give off different colors of light. This allows us to make a whole host of different colors almost at will.
It may be difficult what you had to do to get different fluorescent colors on other molecules. Basically, you needed to synthesize and test and make tiny adjustments. And the process to make the fluorescent dyes may be completely different. Quantum dots, in theory, can be scaled up very easily!
Stability and efficiency are other major benefits of using quantum dots. These suckers don’t easily get photobleached, and they glow incredibly brightly. This means that we can use them for traditional microscope imaging. It also means we can even take the technology into the body and analyze in real time. Take a few examples:
There is a cell biologist named Clare Waterman with some…quirks, let’s say. She’s also a huge, pioneering geek in microscopy and fluorescent imaging. As such, she demonstrated her enthusiasm by having a tattoo of a mitotic spindle injected with quantum dots. I cannot acquire an image here, but if you Google “Clare Waterman quantum dots tattoo,” you’ll see what I mean.
In body imaging
A more useful application of quantum dots has been discovered recently. By tagging the dots to different molecules, they can be tracked to parts of the body. One amazing story came out where researchers took advantage of mouse anatomy to image the lymphatic system, with this picture as a result:
Fluorescent quantum dots in a live animal and post mortemImage Source: “In vivo real-time, multicolor, quantum dot lymphatic imaging.”
What you are seeing there is a published image where a mouse was treated with quantum dots either orally or by different types of injections. The researchers were able to follow in a live mouse exactly where the quantum dots ended up, in this case the different lymph nodes.
Researchers hope to take this concept further and tag quantum dots to antibodies in order to visualize tumors without using radiation.
That’s all I have for today about quantum dots. I have a feeling they’ll be turning up in more scientific work in the future, though!
So I was perusing the science blogs, and I found a delightful post over at Chemical Engineering News:
I enjoy her blog immensely. She is helping to bring down the lofty engineering concepts down for the rest of us. Engineering is something I’m interested, but my biomedical studies have kept me pretty ignorant to it.
Of course, I encourage anybody to go read her blog for the full scoop, but this is quite an amazing finding, a material that is only twice the density of hydrogen. Aerogels hold a lot of promise in terms of insulation and materials. They are so light, yet they can still act as effective traps of heat. Aerogels can also be made transparent, making them useful for insulating things like windows and skylights.
You can even buy some aerogel, though not in the form that has recently been discovered. If you are a purveyor of ThinkGeek, then you’ve probably seen this product:
And that tells you a bit about the problems associated with aerogel. Right now, it’s pretty expensive. Consumer-grade stuff runs at 40$ for around two grams, so I’m not so sure about the economic viability of aerogel at this time. It’s really neat to think about the possibilities, though!
Head over to Paulina’s blog and check out the full story!
So in a previous episode of Really Cool Things, I showed you a little bit about the principle of fluorescence. This was where certain molecules are able to take light of a high energy (like ultraviolet radiation) and spit out visible light.
Today, I want to focus more on those molecules
The fluorescent molecules have a lot of special qualities that make them pretty unique in nature. They tend to have a lot of what is called aromaticity, basically the ability to move and share electrons around the entire molecule. This allows the electrons to be excited pretty easily without crashing back down too fast.
The first fluorescent molecules were characterized in the 1800s, when scientists thought that light was bouncing off materials in a special way. The study of quinine by George Stokes was the first to introduce the term fluorescence.
flouresceinImage taken from CyberChemist on Flickr
The dye fluorescein was not the first fluorescent molecule discovered, but it was among the most important. It was synthesized in 1871 by the future Nobel laureate Adolph von Baeyer (in part because of the synthesis of this dye). At first, fluorescein had limited use, but the development of the ultraviolet microscope in the early 20th century led to its use in cell biology.
A derivative of fluorescein, FITC1, gained use in the 1940s when it was attached to antibody molecules, giving birth to the field of immunofluorescence (more on that in a future post!).
Interestingly, while fluorescein has fallen somewhat out of popularity with cell biologists, this molecule is still used widely in the field of ophthalmology! Fluorescein angiographs allow doctors to detect changes in the eye that may be indicative of disease
StargardtsThe retina of a patient with Stargardt’s macular dystrophy. Here’s lightning in your eye!
Unfortunately, there is a big problem with the first-generation fluorescent dyes, and that is photobleaching. This refers to the phenomenon where the dye stops being able to absorb and emit light, often due to damage to its structure. Fluorescein is pretty unstable in this regard, to the extent that it becomes necessary to shield it from light as much as possible when working with it, lest it start to break down.
The solution? Better dyes! Molecular Probes has a whole line of different Alexa Fluor dyes that are derived from fluorescein but are much more photostable. There is also a very wide range of colors to pick from, giving you aesthetic and practical flexibility in your work.
DyLight-Labeling-Product-Spectrum2-650pxA variety of colors is available for Alexa Flour dyes
These dyes are used all the time in a variety of technique, not the least of which being immunofluorescence.
Fluorescent dyes are very interesting little monsters, and there’s more where that came from! Future posts will cover other molecules that allow us to get fluorescence, improving upon the dyes even further. Stay tuned!
1 Fluorescein isothiocyanate
My wife over on DIY on a Budget prepared a post the other day about a pressure cooker recipe that turned out very nicely. If you like roast, I definitely recommend that you check it out! She got a comment on there wondering what the difference between pressure cooking and a slow cooking was. She turned her reply into the Longest Reply to a Comment Ever (patent pending).
I thought…what an interesting topic! What is the deal with slow cookers and pressure cookers?
So most of us get the basic idea of a slow cooker. Put your food in. Set it and forget it. Eight hours later, BOOM. Dinner. Congratulations on your well-deserved food stuffs.
We also know how pressure cookers work. Put your food in. Set it and forget it (don’t forget to vent or else you may have an explosion on your hands). Fifteen minutes later, BAM. Dinner. Congratulations on your HOLY CRAP IT’S WAY TOO HOT TO EAT.
But is that time difference really all there is to the two? Why does pressure make such a big difference in the first place? Let’s explore…
Slow Cooker versus Stovetop Cooking
The principal behind slow cooking is relatively low temperatures sustained for a long period of time. Stovetops are usually pretty good about getting things hot quickly. They aren’t so great at sustaining a low temperature for a long period of time, partially because the pot you set on the stove has a pretty large area to lose heat. Basically, the bottom of the pan touches the burner, and that’s all you get. Too hot on the bottom, not hot enough throughout the food you’re cooking.
A slow cooker uses that big ceramic dish inside the apparatus. This is called a crock, and it stores heat and helps to distribute it evenly, allowing the food inside to cook at the same rate. With conventional stovetops, the risk of burning your food, even with copious amounts of water, is high…especially if you don’t sit and watch it! Low temperatures used by the slow cookers mean it’s very tough to burn your food.
Pressure Cooking versus Slow Cooking
So does the addition of pressure really make that much of a difference? You bet! When you cook things by boiling in a pot, the temperature of the liquid water can only reach boiling, around 100 degrees celsius, before it converts to steam. The steam can certainly get hotter than that, but it escapes from the pot pretty easily! This stinks, because steam is more efficient at transferring heat than liquid water. So you’re limited in how hot you can get your food.
Enter the pressure cooker. It locks in all the gases (for the most part) as it heats up, taking the steam up in temperature with it. As pressure builds, the steam gets hotter, and the water becomes superheated. Basically, you accomplish the same thing as the slow cooker, just much, much faster. And since you don’t lose a lot of heat, less energy is consumed in the process of cooking!
So pressure cookers have a number of advantages over other cooking devices. Your time and patience will determine which one you want to use. Pressure cookers are also a little more difficult to use and can be more expensive. Checking your food in the middle of the cooking process for taste is nearly impossible in a pressure cooker, as well. So think carefully before choosing!