April 01, 2016 at 12:28AM

Today I Learned: 1) Willow trees* in Florida have an interesting relationship with American alligators. The willow tree grows at a very specific altitude of about a foot, where it has ready access to water without being actively waterlogged (which would presumably be a difficult position for a willow sprout). Most of the best places for willow trees to grow are on stone outcroppings of some sort, including limestone and sandstone. These rocks end up donut-shaped, with a pool in the center, thanks to alligators -- alligators really like to bask under the willows, and many years of many alligators shuffling around under the willow scrapes out a depression in the rock on which it sits. This makes a little pool of water... which is perfect for an alligator to sit and and wait for prey to come by. Today's tree fact brought to you by Mengsha Gong. * not the weeping kind, another species. 2) Those of you who design primers often, this one's for you. When you design primers, ever wonder what those "self 3' complementarity" and "self complementarity" scores are? I did. Today I learned what they are. "Self complementarity" is a somewhat abstract score that measures how well a primer will dimerize. The self complementarity score is calculated by finding the best alignment of the primer against another copy of the primer. Once an optimal alignment is found, the self complementarity score is calculated as the number of correctly-paired nucleotides minus the number of incorrectly-paired nucleotides, with an extra penalty for gaps and less penalty for a pair with an "N" in it. I'm pretty sure the algorithm doesn't allow scores less than 0. You can see the full description of the algorithm (which is pretty short) here: http://ift.tt/1M4WO1z "Self 3' complementarity" is a related measure of how likely primers are to prime off each other. It's the same as the self complementarity measure, except that the "best" local alignment is restricted to be one where the 3' end is anchored, which would allow amplification off that primer. Full algorithm details here: http://ift.tt/1SqIaOR 3) Why the Boltzmann distribution describes probabilities of states based on energy level! I'm not going to go into the full explanation here, because I don't think I can do a better job than this source: http://ift.tt/1M4WOyo (it's 6 pages at high-school level math, one of which is a table and one of which is totally skippable if you're not specifically interested in statistical QM (everything after BD-5) -- definitely worth a read if you want to see why thermodynamics works). I'll try to give a short preview, though. You can get to the Boltzmann distribution by considering a small, finite number of particles (or springs or coins or molecules or whatever) with discrete energy summing to some constant total (since energy is conserved in a closed system). You can enumerate out all the possible ways to distribute the discrete lumps of energy to the particles -- each assigment of a unique energy to each particle is a microstate, and every collection of microstates with the same overall distribution of energies (i.e., two particles with zero energy, five particles with one energy, and one particle with two energy) is a macrostate. You take the limit of that distribution as the number of particles gets really big and the difference between energy levels goes to zero, and you get a Boltzmann distribution. One thing that explanation *didn't* cover at all was how temperature gets into the equation -- the author just shows that the distribution of states has the form αe^(β-E(s)), where α and β are some constants, but they don't show why β ends up being 1/kT. Thanks to Dean Clamons for finding this wonderful little gem!

March 31, 2016 at 03:02AM

Today I Learned: 1) Thermodynamics! Specifically, why temperature plays the role it does in chemical reactions, as reasoned from the Boltzmann distribution. If you're well-versed in statistical mechanics, you probably aren't going to learn anything from this post. For the rest of y'all, I'm going to try to explain the role temperature plays in chemistry, using basic statistical mechanics. You'll need some high school algebra, internet access and a browser capable of using wolframalpha.com, and some patience (yeah, these thermodynamics TILs tend to end up pretty long). I'll also be writing out equations, and Facebook doesn't make writing out equations particularly easy. It should be pretty straightforward if you follow along on paper. First, let's define a state. That's pretty simple -- a state is an arrangement of atoms (and their momentums) of some collection of atoms. Actually, it doesn't have to be atoms -- you can apply statistical mechanics to anything where you can define states, energies over states, and temperatures, but atoms are the usual agents in thermodynamics. Let's consider a super-simple system consisting of a coin with the states "lying flat on a table" (I'll call it "FLAT") and "standing on its edge" (I'll call it "EDGE"). States are said to have an energy (or, more fomally, a Hamiltonian) that describes in a number how "stable" a state is (there are other ways to interpret what an energy is -- I don't have a way to explain it from first principles). The lower the energy of a state, the more stable it is. Let's assign some hypothetical energies to the coin states. The FLAT state is much more stable, so we'll give it a lower energy. Lets say FLAT has energy 1, while EDGE has energy 1,000. One of the more fundamental results of statistical mechanics (which I'm taking as brute fact) is the Boltzmann distribution. Statistical mechanics tells us (again, as I'm taking as brute fact) that systems with certain properties follow the Boltzmann distribution (basically, where you randomly sample states A LOT, which is generally true for chemistry and which we will assume is true for the coin example by assuming we either observe a hell of a lot of coins or we come back to the same one over and over again, with enough time in between that we can't predict the state of the coin from the last state it was observed in). What's does that mean? It means this -- the probability of a system being in a state x is proportional to e^-(E(x)/kT) where e is the number e, E(x) is the energy associated with state x, and T is the temperature. Oh, and there's k, the Boltzmann constant, which is an extremely important cosmologic constant and super-important for making units work out in this equation... but it's also just a number, so I'm going to drop it from here on out*. So, what does this say? It says that as the energy of a state gets higher, the probability of that state goes down essentially exponentially. I say the probability of a state is *proportional* to the thing above, but what's the *actual numeric probability* of a state? To find that, we use the fact that the sum of the probabilities of all of the states has to add up to 1, which means that if you divide the above thing by the sum-of-those-above-things-for-all-possible-states, you get the actual probability of that state. Written out, p(x) = e^-(E(x)/T) / Σ(e^-(E(s)/T)) where the sum is over all states s (this would be a good place to start following along on paper, if you aren't already). This is super-important, because it means the probability of each state is affected by the probabilities of all other states. Ok, so what's temperature doing in this equation? Let's consider the coin example again. What's the probability of the coin being on its edge, according to the Boltzmann distribution? There are only two possible states, so it's pretty easy to write out that equation above: p(EDGE) = e^-(E(EDGE)/T) / (e^-(E(EDGE)/T) + e^-(E(FLAT)/T)) There are a lot of terms with T in them up there. We can simplify things by dividing the numerator and denominator through by e^-(E(EDGE)/T), yielding: p(EDGE) = 1 / (1 + e^-(E(FLAT)-E(EDGE)/T)) That's much nicer. Lots more 1's, much fewer T's. Note that this is basically a simple function of two variables: there's T, the temperature; and there's E(FLAT) - E(EDGE), the difference between energies of the two states**. Let's call that difference X. To get an idea of what this function actually looks like, check it out on wolframalpha.com with T = 1 (http://ift.tt/1pMv7Qq). Positive values of X mean that FLAT has a higher energy (is less stable), while negative values of X mean that EDGE has a higher energy. If the two states have the same energy (X=0), then p(EDGE) is 0.5 -- the two states are equally likely. As X gets higher (FLAT has higher relative energy), the probability of EDGE gets higher pretty quickly, until it effectively saturates at 1. As X gets lower (EDGE has higher relative energy), the probability of EDGE drops dramatically until it bottoms out at 0. This matches intuition -- the more stable (lower-energy) state is much more likely. For our example, we said that E(FLAT) = 1, while E(EDGE) = 1000, so we're WAY off to the left -- FLAT is extremely unlikely. That's at temperature 1. What happens if we turn up the heat? Well, the only thing T does in the equation above is to modify X. Specifically, T acts to *scale* X -- as T increases, X/T gets closer to zero. It's kind of like the X-axix gets stretched out; or, equivalently, raising the temperature pushes you towards X = 0 in the plot I linked to above. As an example, let's try turning T up to 1000: http://ift.tt/1M2hA1D. Now you can see that 999 difference in energy isn't so much -- EDGE is now relatively likely. Raising the temperature *flattens out* the probabilities of different states by moving them from the edges of our probability graph toward the middle (http://ift.tt/1pMv5YT to see the probability of EDGE as a function of both X AND T). Conclusion: high temperature makes all states equally probable. Low temperature makes low-energy states much more likely. Now, at this point, if you're like me, you're thinking something's terribly wrong with this picture. After all, when you turn on your stovetop burner, your water doesn't start taking on random states. It does something very specific -- it heats up, then boils. What gives? To understand what's going on here, we have to think about the *microstates* of the pot of water vs its *macrostates*. The *microstates* of a system are really what I've been talking about above -- they're all of the possible arrangements of atoms in a system. That's too many atoms to individually track, so we usually talk about the *macrostate* of a system, which is a collection of techncially different but experimentally indistinguishable microstates. For instance "the water is liquid" is a macrostate -- there are bazillions of ways you can arrange the molecules in that pot of water that will still look liquid, so we call it a single macrostate. "The water is a vapor" is another macrostate. Some macrostates have a LOT MORE possible microstates than others. We say that those macrostates have high "entropy". That's all entropy is -- the number of microstates that look like a macrostate. What's happening when you boil water is that water vapor has MASSIVELY more states than liquid water, but microstates that look like water have much lower energy. When the temperature is low, the low-energy states are favored strongly, and your pot of water stays bound together as a liquid. When the temperature is raised enough, suddenly the probabilities of all of the states become more or less equal***. But! There are tons more "water is a gas" states than there are "water is a liquid" states, and when you add together all of the tiny-and-equal probabilities for the water-is-gas microstates, they collectively massively outweigh the sum of the probabilities for the tiny-and-equal water-is-liquid microstates. In other words, higher entropy macrostates are favored at high temperature. And there you have it -- the mathematics behind why low temperatures favor low energy and high temperatures favor high entropy. * If you're not comfortable with my dropping constants randomly, just pretend that for the rest of the TIL, T is actually the Boltzmann constant times temperature. ** You may have heard that there's no thing as absolute energy, only relative energy. Perhaps this gives some intuition into why -- if you add some constant amount to all of the energies of the states in a system, the resulting distribution of states is indistinuishable. *** I suspect, but have not yet convinced myself, that the exponential-looking shape of the plot of microstate probability around 0 energy difference are at least part of why you tend to see sharp phase transitions when you raise the temperature in a lot of setups -- changing the temperature mostly slides you around the flat tails of that distribution, where microstate probabilities aren't really affected much, until you suddenly hit a bit where microstate probabilities start exponentially moving away from 0 and 1. This produces a relatively sharp transition from an energy-dominated regime to an entropy-dominated one. The trouble is that temperature change doesn't move you linearly in that graph, and I don't have a good enough intuition for exactly how it does move you -- can anyone confirm or deny? Chris Lennox? Robert Johnson? Suzannah Fraker? Andrew Andy Halleran? Anders Knight? 2) Portable soup! Portable soup is the ancestor of modern boullion cubes. Portable soup was invented in the 18th century as a food for sailors. It's basically a soup, concentrated down to a thick gelatinous substance that can be stored apparently indefinitely. You can either dissolve it back into soup or just chew it. Portable soup was used as foodstuff in the Brittish Royal Navy until around 1815, at which point research suggested that it wasn't actually particularly good for sailor health, and was replaced by canned meats. Thanks to Tara Sullivan for enlightening me about portable soups. Many more juicy details on the portable soup wiki page (no joke: http://ift.tt/1SpBCRV) 3) ...how negative autoregulation can make genetic responses faster. See, the amount of a protein a cell has is determined by two factors: how quickly that protein is produced, and how quickly that protein is broken down (or diluted out). It turns out that the *speed at which a cell can change* the amount of protein in the cell is largely determined by the speed of degradation. Yes, if you're turning on a gene, you can make it respond faster by cranking up the production rate, but then you end up producing a lot *more* of that protein in the end, so you need to couple that with a higher degradation rate anyway to maintain the same steady-state protein level. ...unless the gene represses itself. Then you can have a high initial production rate when the gene is just turning on, which gives you a fast 'on' response, but the gene can regulate itself to whatever steady state you need. Note that this doesn't help at all with *deactivation* of a gene -- then you're still limited by how quickly the protein is degraded. * when a gene represses its own production Bonus fact, courtesy of Mengsha Gong: The cluster fig, though a beautiful tree, is an interesting kind of nusiance plant -- its roots are really, *really* good at finding water, and will happily search out pools, septic tanks, and sprinkler systems.

March 30, 2016 at 02:57AM

Today I Learned: 1) Mangrove trees live in brackish water. They're one of the few species of trees that can. But mangrove trees use the same intracellular concentration of salt ions as other plants (or at least a concentration closer to other plants than to the water they live in). How do they deal with the excess salt they soak up? According to Mengsha Gong, mangrove trees deal with salt by selecting certain leaves to be salt sinks. They load up the leaf with tons of salt, then drop it. Kind of a waste of a leaf, IMHO, but I guess it's worth it! 2) Baobab trees are awesome. The most notable feature of a baobab tree is its giant, waterlogged trunk -- baobabs live in climates where it only rains about one month of the year, and in that month it rains torrentially. Baobabs take full advantage of this rainstorm by soaking up TONS of water in their giant, sponge-like trunks. The interior of a baobab tree, therefore, is basically sopping wet. Among other things, this is very attractive to elephants, who will mow down smaller baobabs and carve chunks out of older baobabs for the water. The second most notable feature of a baobab tree is its quickly-regenerating bark. Because elephants really like taking chunks out of the sides of baobabs, the trees have evolved to grow back quickly relative to other trees. They can also survive being ringed, so humans living in areas with baobabs will cut large swaths of bark off the tree to make clothing. This fact also courtesy of Mengsha Gong. 3) My feet are a half (US) shoe size smaller than I thought.

March 29, 2016 at 01:50AM

Today I Learned: 1) ...that there's no direct linkage between the brain and lymphatic system. EXCEPT THAT THERE IS! UVA researchers have just discovered previously unknown lymphatic vessels entwined in the membranes surrounding the brain. This is big news for understanding neurological disorders with possible immune components, like Alzheimer's Disease. Got this information here: http://ift.tt/1USeccq Thanks Sarah Seid for pointing me to this! 2) ...a bit more about Kalman filters. In brief, a Kalman filter is an algorithm you used to guess at the state of a changing system (example -- the temperature of a pot of water, or the position of a moving car) from a potentially noisy set of measurements (example -- a bunch of inaccurate thermometer readings, or noisy GPS locations). In particular, a Kalman filter is the *optimal* algorithm for finding the maximum-likelihood solution for a particular Bayesian inference problem roughly equivalent to a hidden markov model with continuous state values and Gaussian noise. I knew that Kalman filters were supposedly "optimal", but I didn't know what that meant, exactly. Until today! 3) Not really a Thing I Learned as a Number I Crunched, but I thought this was a kind of interesting number -- a typical table is, order of magnitude, several tens of billions of atoms across. That's WAY smaller than I would have naively predicted, but I guess that's because when I think of Numbers of Molecules in things, I'm usually thinking about volume, and volume is, in some sense, much bigger than length.

March 28, 2016 at 01:55AM

Today I Learned: 1) ...a bit more about loop-mediated isothermal amplification, or LAMP (don't ask me how it got that acronym). LAMP is a specific, complicated form of PCR, which means it uses a polymerase to quickly and massively amplify a DNA target. Exactly how LAMP works is a bit much for me to explain here -- if you feel you're equipped to nerd out over PCR methods, check out NEB's video primer* here: http://ift.tt/1UR04jt. The gist is this: LAMP is more complex than the usual method of PCR, requires more primers, and makes a variety of multimeric chains of the target sequence instead of clean individual copies, BUT it can be performed entirely at room temperature just by mixing the primers, polymerase, buffer, and target, and only takes 10-20 minutes to run. This makes LAMP potentially really awesome for diagnostic applications, where a) the targets are more or less fixed, so you don't have to re-design primers all the time; b) you need super-fast results; and c) you don't want to have to be able to use a thermal cycler to use the diagnostic. * I couldn't help myself 2) There is a nice little stall in Pike Place, Seattle, that sells homemade pastas with incredible flavors. They well a habañero pasta which they warn is quite spicy. Today I learned to take that warning seriously. It did not need to be put in a spicy dish to work. 3) ...how to use the printers in SFL. Apparently when you print to them from a computer, they're put in a queue until you physically go to a printer, log or swipe yourself in, and tell it to print the job. I didn't have to do this last time I was in SFL, so this must be a new thing....

March 27, 2016 at 02:24AM

Today I Learned: 1) Estivation and hibernation are not the same thing. Hibernation is slowing down metabolism to survive cold; estivation is slowing down metabolism to survive heat. Ants hibernate, not estivate. Thanks to Dorothy Fontaine for setting me straight on this one! 2) So you know how the US legally abolished slavery in the 1860s? Well, Britain beat us to it -- the Slavery Abolition Act of 1833 legally emancipated slaves under the age of 6, and reclassified slaves over the age of 6 as apprentices, who would be phased out of apprenticeships over the next seven years. Slave owners were compensated for their losses, to a staggering tune of about £20 million, which is roughly equivalent to £70 billion today, and was 40% of Britain's expenditures for that year! 3) The ancient Greeks (and, therefore, much of Europe for most of known European history) apparently believed that the uterus was a sort of "animal within an animal", capable of moving around the body, and that wombs wandering into the wrong places could cause a number of illnesses and disorders.

March 26, 2016 at 03:37AM

Today I Learned: 1) Apparently banana plants are really difficult to kill (unless, you know, you're a banana blight). The reason is that banana trees form rhizomes, which are bulbous little root balls that can grow back an entire tree if the rest of the plant is killed. In fact, when bananas are harvested from their trees, the trees die off and are re-grown next season somewhere else in the root system. Also, regarding bananas, there are "variegated" banana varieties, which are striped in different shades of green. And yes, the fruit is striped too: http://ift.tt/1PwqmzG Thanks to Mengsha Gong for today's banana facts! 2) Ants have a surprisingly large range of eyesight-ability. Some are essentialy blind, and can only distinguish between large differences in illumination. Other species have great visual acuity for a creature of their size, and can distinguish motion from a meter away (!). Most ants fall somewhere in the middle -- they can detect ambient light pretty well, can see at very close ranges just fine, but can't see much detail at range. More importantly for my purposes, apparently most ants can't see well in red, so you can illuminate an ant nest with red light without freaking out the ants. (this may actually just be because humans can see better in low-light conditions when that light is red, so you can see without using as much light. I'd have to find some actual ant research to tell) 3) Apparently insurance companies make razor-thin margins when it comes strictly to payments and payouts, and some even pay out more than they receive in premiums. Where they actually make their money is in *investment*, which they can do very efficiently because they've lumped together lots of peoples' money in one pot. Thanks to Asher Rubin on this one!

March 25, 2016 at 04:29AM

Today I Learned: 1) ...that controlled fires are an important tool for management of the Florida Everglades. In addition to the usual benefits of controlled fires (recycling of nutrients, clearance of possible uncontrolled fire triggers, etc), fire is particularly useful in the Everglades for clearing out invasive species from cyprus groves -- the cyprus trees are *much* more resilient against fire than any invasive plants, so fire really does purify the groves. Thanks Mengsha Gong! 2) J. Craig Venter (or, more accurately, the J. Craig Venter Institute) has made a new minimal synthetic genome! It's a stripped-down version of Mycoplasm mycoides, which is the same species JCVI used in their last minimal genome paper two years ago. M. mycoides is a good candidate for building a minimal genome because it's already quite small (901 genes). This is probably because M. mycoides is parasitic, and doesn't synthesize a lot of its own metabolites. In any case, the newest version of M. mycoides, dubbed syn3.0 by the research team, has 473 genes. Of those, 149 have unknown function but are required for growth. It has a doubling time of about three hours, which is slow, but not *absurdly* slow -- for reference, that puts it on par with many cyanobacteria for replication rate. A number of people independently alerted me to this story today, including Science Magazine. Primary article at http://ift.tt/1UMC0yg, but it's Science so it's almost certainly paywalled unless you're at an academic institution. Science also has a review article here (http://ift.tt/1T7YsRo) that should be free -- please let me know if it isn't and I'll find a better one. 3) ...about the Credence Calibration Game (see http://ift.tt/1dzDceM). The idea of the game is to train yourself to correctly estimate your confidence on statements. It goes like this. The game asks you a question, like "which country has the higher GDP, France or Saudi Arabia?". You give an answer, and a confidence (50%, 60%, 70%, 80%, 90%, or 99%). If you guess right, you get points; if you guess wrong, you lose points. The higher your reported confidence, the more points you get/lose. Theoretically, the point values are calibrated so that you do best if you correctly estimate your confidence (i.e., you should be getting 50% of your 50% confidence answers correct, 60% of your 60% confidence answers correct, etc). I've seen this game in a couple of forms, but this one's nice because it's a discrete, downloadable app that's totally automated (no tallying points yoruself) and a tight gameplay loop. Go check it out if you're interested in improving your own probability estimation performance!

March 23, 2016 at 11:34PM

Today I Learned: 1) Oh reddit. Oh my. http://ift.tt/1q3bT9L 2) The cost of synthesizing a plasmid, de novo, from Transcriptic, is about $250-350. Synthesizing libraries of a few hundred parts will set you back several tens of thousands of dollars. I guess I should have seen that coming. 3) There's a cool way to sort molecules by size, whose name I forget, but it's some subset of size exclusion chromatography. Like any chromatogrpahy, the basic premise is that you run a liquid sample of mixed molecules through a column that causes some molecules to run faster than others, based on some chemical property of the molecule. In this method, it's size. The way the column works is that it's filled with large beads that are honeycombed with little holes. Liquid can flow between the beads, but also through the beads. Large molecules can't fit inside the pores in the beads, so they flow around the beads. This makes them flow relatively quickly through the column. Small molecules *can* enter the pores, but it's hard for them to get back out again, so they tend to flow relatively *slowly*. This goes against all the usual intuitions of size-based chromatography (or, for us molecular biologists, gel electrophoresis). Thanks Anders Knight!

March 23, 2016 at 02:19AM

Today I Learned: 1) The gauzy, veily stuff used to make wedding dress trains and tassles and veils is called "tulle". 2) Sodium and potassium have unusually low melting points for metals, at 98°C and 63°C, respectively. You could melt both of those in a pot of boiling water, easily. I wouldn't recommend it, though, as both would explode on contact with the water. I guess we never see either as a raw metal very often. 3) Operating costs for an aquarium with ~10 full exhibits is, order-of-magnitude, several tens of millions of dollars per year. Roughly half of that money goes to personel costs. This assumes that the budget of the Aquarium of the Pacific is typical for an aquarium of its size. Source: http://ift.tt/1Rfvyxp

March 21, 2016 at 10:43PM

Today I Learned: 1) Chopsticks was written in the late 19th century by a 16 year old girl (under a male pseudonym, surprise surprise). In the original score, the pianist is instructed to play with the hands sideways, little finger down, making chopping motions to play each note. 2) I have a new contender for 'safest chemical besides water' -- DFHBI-1T, a dye that lights up green when it binds to an mSpinach or mBroccoli RNA domain. Check out the MSDS: http://ift.tt/1Rwa7Kq. The only even vaguely dangerous-sounding thing I can see there is that it shouldn't be stored with oxidizers. For some reason. It isn't even known to contain any chemicals known to the state of California to cause cancer, birth, or any other reproductive effects, and that's saying something! And yet, it still recommends safety glasses. Is that really necessary? (bear in mind also that DFHBI is quite expensive and difficult to get in amounts greater than a few tens of milligrams.) 3) Today I tried out Benchling for the first time. Benchling is an online lab notebook and DNA-visualization tool. It's used for a combination of day-to-day record keeping and information storage of plasmids, primers, and other DNA-related things. With a good internet connection, it's actually pretty nice, and snappy enough to be worth using. The interface is a tad cluttered, as is usually the case with these kinds of programs, and the zoom functionality for DNA visualization is a bit more awkward than I'd like. Still, I'll keep it in mind next time I need a free plasmid-visualizing solution.

March 21, 2016 at 04:14AM

Today I Learned: 1) When it comes to binomial distributions with very large N, mean behavior is pretty much the entire spread of behavior. 2) ...March madness is ridiculously fast. Less than a week ago, I made my first bracket. Now it's more or less done and graphs of statistics are going up on the internet. Fun facts -- the best human bracket made it 25 rounds before it guessed wrong. The worst bracket made it 21 rounds before it guessed right. Ancillary fact -- the best way to get information on the numbers of perfect brackets is apparently to trawl the twitter feeds. This is ridiculous. I expected better from sports. 3) EPS (a file format that I think is a precursor to PDF? It's often produced by systems like LaTeX, and is usually immediately converted to PDF) has no native support for transparency (alpha). If you want to use semi-transparent figures in EPS format, you're going to have to rasterize them first.

March 20, 2016 at 04:17AM

Today I Learned: 1) Ants can carry liquid drops in their jaws! Some species that feed on nectar-secreeting aphids and other sugar-water-rich food sources will carry drops of nectar home in their jaws. They bring the nectar into the nest, then kind of wave their heads around until an interested ant splits the droplet and takes some of it. After splitting, the ants each imbibe a little of the nectar, then offer the remainder for other ants. They do this several times, until the whole drop is gone. On the topic of ants, today I also learned that most ants, social bees, and other social insects typically communicate with a bandwidth of around 4 bits, which, in terms of giving directions, is the informational equivalent of telling somebody to go "south by southeast". 2) So... here's an interesting story. Back in January, the open access online journal PLOS ONE published an article about the biomechanics of hand coordination while grasping objects. In most respects, it was a normal article, but it contained several lines that sparked instant and vociferous controversy. The lines in question talk about... well, for example, the introduction contains the line "Hand coordination should indicate the mystery of the Creator’s invention." There are two other similar sentences, one in the abstract and one in the discussion. Word actually didn't get out particularly quickly -- it looks like it sat almost entirely unread until early this month, when word got out that PLOS ONE had a paper talking about "The Creator". The journal editors quickly decided to retract the paper, though it's still available for viewing here: http://ift.tt/1T2Fz2i. The authors, who are Chinese, apparently had no idea the word "creator" would be problematic in an English science journal -- in Chinese, "the creator" is apparently a common metaphor for nature, and by "creator's invention" they just meant "the product of natural selection and evolution". It's still a pretty big faux pas for PLOS ONE to not have caught this in peer review, though. Nature recently put out a news piece on the issue, which summarizes all of the events surrounding the paper and its retraction in a surprisingly balanced way (you can view it here: http://ift.tt/1Pk7nIy). I say "surprisingly" because PLOS ONE grew out of a movement against the scientific journal industry, which is best exemplified by Nature and Science. I would have thought Nature would *love* to take the opportunity to slam PLOS given the chance, but apparently they're still too classy for that. If you want to see readers' reactions to the paper itself, check out the comments tab in the paper link I provided above. There's quite a range of responses in there. 3) There is some evidence -- just a smidge! -- that Alzheimer's Disease may be transmissible. The evidence came from the brains of patients who had accidentally been exposed to the prion that causes Creutzfeldt-Jakob disease from injections of human growth hormone derived from human cadavers. Turns out that all of those brains had Alzheimers-like plaques in their brain, despite them being young and having no symptoms of Alzheimers. It's possible that the patients were also exposed to "seeds" of misfolded or aggregated amyloid beta, which eventually grew into plaques. Now, this isn't very strong evidence -- Alzheimerss takes a long time to develop, and there's good reason to think that plaques show up before symptoms. Still, it's an interesting possible twist in the Alzheimerss story. Full story here: http://ift.tt/1T2FBXI This also reminds me of an interesting claim I heard a couple of years ago from a scientist (whose name I unfortunately do not recall) who suspects that the primary causitive agent in Alzheimer's Disease might be a so-far-undetected *virus*. His claim is that the pathology and progression of the disease is typical of an infection, rather than a metabolic disorder or genetic disease or something like heart disease. I wouldn't bet on him being right, but it was an interesting idea and something I've been keeping an eye out for evidence for and against ever since.

March 19, 2016 at 03:33AM

Today I Learned: 1) These things are called "Povitsky bottles": http://ift.tt/1VmhVy2 Apparently they were originally designed for, I quote (from a manufacturer), "preparation of toxins and general tissue culture work". However, I have found no good explanation for what makes them any better than any other bottle for either preparation of toxins or general tissue culture work, other than the fact that a) they're flat-sided so you can put them on a rocker, and b) they're made of glass so you can autoclave them. Mostly the internet is just telling me how to buy them and that they were very important for production of the Salk polio virus. 2) The distinctive animalistic, rumbly vocal style used in many derivatives of heavy metal has a name -- "death growl". Growling in singing may go as far back as 10th century Viking song. Wiki has a quote from a traveling Arab on the topic (though the citation trail for this quote kind of dead-ends quickly, so take it with a grain of salt): "Never before I have heard uglier songs than those of the Vikings in Slesvig. The growling sound coming from their throats reminds me of dogs howling, only more untamed." This and a bunch more beginners' introductions to modern rock and electronica generas here: http://ift.tt/1JB4U0f. Also, this guy has a seemingly endless supply of awesome sci-fi/space opera art. Check out the backgrounds in his dubstep link -- I particularly love the one at 9:21. So many intriguing details! 3) ...a bit more about the relationship between iGEM* and its corporate sponsors. Turns out that it's not quite a simple matter of companies making donations -- by donating enough, companies can put themselves into progressively higher donor "tiers", which give them greater access to iGEM's events, personell, equipment, and participants. Sponsorship can also buy a table at the jamboree (iGEM's yearly conference/competition/meetup) for advertising or information or anything else. In case you were wondering, IDT (Integrated DNA Technologies, not Integrated Device Technologies) is far and away the biggest corporate sponsor of iGEM. *iGEM == International Genetically Engineered Machines, a mostly-undergraduate synthetic biology competition. Participating teams invent new organisms and genetic systems like bacteria you can play minesweeper with, or bacteria that smell like bananas when growing and smell like wintergreen when stationary, or bacteria that detect the edges of shadows.

March 18, 2016 at 01:32AM

Today I Learned: 1) If you cut the mouth out of the center of a jellyfish, the hole closes up without a mouth. The jellyfish will continue to swim around and do all of its normal jellyfish behaviors... except that it has no mouth, so it cannot eat. Apparently they will live for quite a while by cannibalizing their mesoglia, which is the jelly-like stuff that makes up most of a jellyfish's bulk. As they consume mesoglia, they gradually shrink and shrink and shrink until one day they just kind of disappear, presumably having dissolved away. Jellyfish are weird. All of the above has been observed by Mengsha Gong for moon jellies. I have no idea how well it generalizes to other jellyfish. 2) Speaking of jellyfish being weird, jellyfish muscles are *super* weird. Instead of the long, separate, multinucleate muscle fiber cells common to most animals (today I learned that muscle fiber cells are long and multinucleated!), jellyfish muscles are Also thanks to Mengsha Gong on this one. 3) Apparently "apoptosis" is pronounced just about the way it's spelled. When I was first getting into the whole science thing at the NIH, one of my mentors insisted that it was pronounced "ah-poh-toh-sis" (first letter pronounced like the 'a' in 'apple'), specifically with the second 'p' silent. I trusted him on this, but apparently most authorities on the English language (Mirriam-Webster, for instance) keep the 'p' pronounced. I feel like I've been living a lie my whole life.

March 17, 2016 at 04:55AM

Today I Learned: 1) ATc (a chemical inducer used to turn on genes under the pTet promoter and related promoters) is toxic to bacteria in a dose-dependent fashion when used in concentrations higher than about 200 µg/ml. This really shouldn't be surprising, since it's a chemical analogue of tetracycline, which is an antibiotic, but it's still good to know. 2) ...that there's a second VWR stockroom on campus! It has wares that overlap with the one I always use, but not completely. Notably, it has a wider variety of tubing, which I could use. There are also rumors of a third stockroom somewhere...? 3) I'm having difficulty finding information to corroborate this, but apparently there was an old game console controller that was designed to be plugged into a plant. It would read random electrical signals in the plant as input, letting you play video games against a plant. Andrey Shur, can you confirm the existence of this hardware?

March 16, 2016 at 03:49AM

Today I Learned: 1) Today I started learning how to mod for Xcom 2. Learning how game modding works is one of the side-things I've been meaning to do for a while now, and today I began. So far, it looks pretty simple -- many mods can be done more-or-less by changing configuration files, though the Xcom 2 modding kit has nice programmatic ways to do that in a somewhat version-controlled fashion. Unfortunately, for what I plan on doing, I'm going to need to change more than a couple of config files.... 2) Pepper spray is just capsaicin. Well, not *just* capsaicin -- it's about 1% capsaicin, which is ridiculously high percentage. Still, it's basically concentrated hot sauce. This surprised me, because I always thought pepper spray was similar in mechanism to the active ingredient in onions, which produces sulfuric acid when it dissolves in water in your eye or throat or nose. ...or does it? I did a little googling to double-check myself, but I found mixed answers from different sources. The most legit-looking sources make no claim about onion gas producing sulfuric acid, instead talking about its effect on receptors and nerves. The only actual experimental result I found was from a fellow internet-surfing skeptic: http://ift.tt/1LpWav2 Thanks to Mengsha Gong for sending me down this road! 3) From the same source as I just linked in #2, some fun facts about volumetric pipettes. It's a short read and has a nice diagram that I can't replicate in text, so I'll just link you to it: http://ift.tt/1WpHn45.

March 15, 2016 at 02:11AM

Today I Learned: 1) A disjunctive sequence is an infinite sequence in which every possible finite subsequence occurs. An important point is that not all infinite nonrepeating sequences are disjunctive. Here's an example: consider the sequence that starts with 0011, then is followed by 00001111, then 0000000011111111, etc. This sequence is infinite. It does not repeat. However, there are plenty of finite sequences containing 0s and 1s that aren't in this sequence. Many real (irrational) numbers have digits that form a disjunctive sequence. In fact, they are so common that if you pick a random (and I mean truly random) real number, it will be a disjunctive irrational number. The most famous irrational number of them all, π, might or might not be disjunctive. Nobody knows. So next time you hear someone claim that every name, every word, and every work of art is contained in π in the right encoding, be skeptical. Many thanks to Andrés Ortiz Muñoz for bringing this fascinating fact to my attention! 2) I'm basically going to quote you an entire super-cute Science Friday segment on this one (thanks to Addgene's facebook page for sharing this!). How many digits of π is enough digits of π? You might feel like there is no such thing -- any finite number of digits is only a truncation of π, a phony invented by humans to approximate the real thing. Well, you're right, but it should be noted that 39 digits of π are sufficient to calculate the circumference of the universe to within the diameter of an atom. For now, that should do. 3) A technique for building diamonds of arbitrary (random) size in the abstract tile assembly model (aTAM) using only 11 tile types! My best design used 22. What a time to be alive! Thanks to Aileen Cheng for showing me her formulation.

March 14, 2016 at 01:12AM

Today I Learned: 1) Transcripts degrade exponentially in TX-TL* with a half-life of approximately 18 minutes. It's beautiful how clean the results are... except when they're at high-concentration. Then they decay exponentially for a few hours, then rapidly switch to a *slower* exponential decay. As far as I know, it's not known what causes the transition in degradation behavior. * E. coli guts extracted to use as an in-vitro prototyping environment for DNA circuitry. 2) Got to be a little more careful with cooking wine... it has a stronger effect than I anticipated on fried rice. 3) Not really something I've learned, but a hypothesis to test... I've recently moved my young Novomessor cockerelli (ant) queen into a new enclosure. For the first few days, her workers spent a lot of time in their outworld, which is a basin attached to the nest for the ants to forage in. After a couple of days, I opened up more of the next for the ants to check out, and they quickly moved all the way to the back, right above where I installed a little heating pad. Since then, I haven't seen the ants come out into the outworld. I assumed the reason was because the ants had fed themselves sufficiently, and had switched to taking care of the queen. However, it occurred to me today that the day I opened up the enclosure coincided closely with when I turned the temperature down in the apartment. Ants are very sensitive to temperature, and it's quite possible that they're not going into the outworld because it's too cold out there. To test this, I've turned up the heat in my room to around where it was before. We'll see if the workers start exploring around again.

March 13, 2016 at 12:38AM

Today I Learned: 1) There is a subreddit for turtle facts. Of course there is a subreddit for turtle facts. http://ift.tt/1ResFyP. Check it out. A few gems from the subreddit front page: moss is really important for most species of turtles kept as pets, as they get stressed if they don't have something to hide in; painted turtle females store sperm from the males they mate with for future fertilization; turtles get cataracts in much the same way as humans, and recently a ~100 year old snapping turtle by the name of Darth Vader became the first turtle to receive cataract surgery before being released into the wild. 2) Newly hatched* platypus babies are ridiculously small. They look more like fetuses than platypuses. Check out http://ift.tt/1MfgZUT to learn what a baby platypus looks like. * Remember, not only do platypuses have bills, incredibly painful venom, and have five pairs of chromosomes, they also lay eggs. 3) Satellite debris is a serious threat to spacecraft. Today I learned the extent of that threat -- according to Wiki, there are about 2,000 satellites in orbit at a time these days, and about one is destroyed by debris collision every year.

March 11, 2016 at 11:54PM

Today I Learned: 1) You know that thing that people used to do where you send messages to someone encoded in different species of flower in a bouquet or similar arrangement? Today I learned that that's called "floragraphy", and it can get quite specific (but I won't). 2) Tin foil over the end of a tube is not sufficient to keep that tube sterile. Better keep it in ethanol next time. 3) Magnets make everything better. Well, maybe not everything, but they *are* an awesome thing to add to small lab equipment that you want easy access to. Consider, for example, your favorite pen. Tape a strong little magnet to this pen, and you can stick it to anything metal! (fume hoods are particularly convenient) If you want to be able to stick it to anything else, then just tape a metal razor to that thing, being sure to cover the whole razor so it's safe. (incidentally, magnets are also a convenient way to store razors, if not the safest. I think I still prefer tape-pockets for razor storage).

March 11, 2016 at 02:49AM

Today I Learned: 1) Amphiphilic peptide membranes. Consider a cell membrane. Cell membranes are usually phospholipid bilayers, which is a fancy way of saying they're basically a soap bubble made from a ton of insoluble hydrocarbon chains (lipids) with phosphate groups at one end that are soluble (phospholipids), which organize into a double-layered sheet with the heads facing out towards water and the tails facing inward towards each other. In principle, you should be able to build such a membrane out of any molecule of roughly the same shape (long and thin) and size with a charged head and a long, insoluble tail. Well, some clever chemist came up with another class of molecule that fits the bill -- amphiphilic peptides. These are very short proteins (amino acid chains) where the first amino acid is charged and the rest form a long, hydrophobic backbone. In in-vitro conditions, they can spontaneously form micelles and bilayers just like phospholipids, although so far they've all been pretty small (tens of nanometers at the largest). Why would you use amphiphilic peptides instead of phospholipids? After all, phospholipids are good enough for nature*, why aren't they good enough for us? The answer is their programmability. Because amphiphilic peptides are, well, amino acid chains, they can be genetically encoded. If they can be genetically encoded, they can be easily modified. I'll leave it at that for now. Thanks to Anders Knight for cuing me in to amphiphilic peptide membranes! He's been reading about them extensively over the last 24 hours or so, so you should direct any questions about peptide membranes to him (and direct his answers back to me!). * ...or maybe not. See #2. 2) There is at least one context in which the usual phospholipid bilayer membrane design is not good enough for nature, and that's in the extremophiles. Archaea and bacteria living at extremely high temperatures (anywhere from about 50-100 °C) have some really crazy phospholipids in their membranes, presumably because normal phospholipids either break down or fly apart from their neighbors under very hot conditions. Then again, a lot of those lipids can also be found in the membranes of archaea at perfectly reasonable temperatures, so they might not have anything to do with living at high temperatures at all. For more information on archaeal phospholipids than you ever knew existed, check out http://ift.tt/1nBVqHN (apologies if it's behind a paywall). In particular, check out figure 1, which shows a bunch of interesting archaeal and bacterial lipids. My favorites are caldarchaeol (1d) and cyclopentane-containing caldarchaeol (1f), which have two phospholipid heads! 3) "Psychrophilic" is another word for "cryophilic", which is used to describe organisms that grow in extreme cold (between -20 and 10 °C).

March 10, 2016 at 02:37AM

Today I Learned: 1) There are multichannel pipettes that can switch between spacing for 96-well plates (the usual multichannel pipette spacing) and for 384-well plates (which have wells closer together)! #pipettes (Also, there are 96-well pipettes. They pipette 96 wells at once. Mind. Blown.) Thanks to Andrey Shur! 2) There have been a number of controlled, blind studies to determine whether Stradivarius violins are detectably "better" than either other good contemporary violins or good modern violins. According to those studies, Stradivariuses are consistently on par with other super-good violins, but never unambiguously better. Also, many of the better-quality Stradivarius violins (made between 1700 and 1725) are named after famous owners, such as the General Kyd Stradivarius, Lipinsky Stradivarius, and Lady Blunt. These exceptionally famous violins are so well-known that a number have been stolen and then recovered after merchants recognized the violin on sale and reported them to their proper owners. Also, today I learned that Stradivari is the name of the family that built the Stradiviarius violins in the 1600s and 1700s. Thanks to Mengsha Gong for getting me to look up Stradivarius Information. 3) ...the story of the crash of Eastern Air Lines Flight 401. This is the most ridiculous crash story I've ever heard, on several accounts. Here's what happened. Flight 401 was doing just fine on its way in to Miami International Airport, right up until it made the landing approach. What the pilots didn't know was that an indicator light had burned out that normally would tell them when the landing gear was down. When they started their approach, the landing gear went down normally, but the indicator light didn't come on like it was supposed to, even after cycling the poor landing gear several times. Instead of manually deploying the landing gear, the Captain of Flight 401 decided to abort the approach, settle into a holding pattern, and check out the problem. Two of the three crew members disassembled the light assembly to check it out while a third went below decks to check manually whether the landing gear was down. So far so good. The only problem is that the crew set the plane to the wrong autopilot -- instead of instructing the plane to hold altitude, they set it to a mode that keeps the plane on whatever course you set with the yoke. Somehow, the yoke was accidentally pushed forward enough to send the plane on a slow decline. If it had been a steep decline, the pilots probably would have noticed. If it had been daytime, the pilots probably would have noticed that the ground was approaching. It wasn't, and it wasn't, and the crew was too distracted by the faulty light to notice that they were losing altitude. For around five minutes, Flight 401 slowly drifted to the ground. Less than ten seconds before impacting the ground, records from the flight voice recorder indicate that the pilots noticed something was wrong with their altitude. Then they hit the ground at 227 miles per hour. The other ridiculous thing about this incident, in my mind, is how many survivors there were. Of the 176 people on Flight 401 when it crashed, only 99 died -- that's a 44% survival rate for a crashed plane. Not too bad, considering the circumstances.

March 09, 2016 at 04:26AM

Today I Learned: 1) Walbachia are a very interesting clade of bacteria that chronically infect insects. Walbachia are *extremely* common, and come in many varieties with many kinds of relationships with their hosts ranging from parasitic to mutualistic. The most interesting ones, from my perspective, are the Walbachia that live either specifically in their hosts' eggs or their sperm. Because they only reproduce through female or male offspring of the host, they are incentivized to maniuplate their host's reproduction toward one sex or the other. And they do. There are a number of mechanisms, most of which involve somehow killing off eggs of the wrong sex, but the effect is that they skew the sex ratios of their hosts, which is really unusual in the animal kingdom. Another cool Walbachia effect -- some Walbachia will kill off any egg they find themselves in with a different strain of Walbachia. I'm a bit surprised they're so scorched-earth about it, but apparently Walbachia don't like cohabitating with other Walbachia. 2) Apparently a common genetic pattern in new endosymbionts like mitochondria, chloroplasts, and certain kinds of intracellular parasites is that the symbiont will very rapidly break a bunch of its no-longer-essential genes (by indels, loss of promoters, mutation of start codon, acquiring new stop codons, etc), then slowly delete those lost genes. This results in extremely rapid (evolutionarily-speaking -- this is still a multi-million-year or tens-of-millions-of-years long process) shrinkage of the symbiont genome, which is how you get things like mitochondria with itty bitty tiny little genomes. It's apparently also fairly common for those genomes to eventually start to balloon up in size again, usually from non-coding RNA. Plant mitochondria are a good example of this -- there are some VERY large plant mitochondrial genomes out there, even though they almost all have the same genes. 3) Speaking of bacteria that live in insects, and speaking of endosymbiont genetics, let's talk about cicada endosymbionts! It turns out that most or all cicadas are obligate symbionts with bacteria that they cultivate inside specialized cells, which are housed in specialized organs. Cicadas cannot manufacture all of the amino acids they need, and their diet is ridiculously poor in protein*, so they have bacterial symbionts that are specialized for amino acid manufacture that give them the amino acids they need to grow. There are lots of cicadas with an apparently wide variety of bacterial endosymbionts, but the talk I atteneded today (by John McCutcheon) was about cicadas of the genus Diceroprocta, which have two (sort of -- we'll get to that) species of bacterial endosymbiont, Sulca and Hodgkinia. Both are really weird-looking bacteria that form giant (multi-micron-long) tubes that seem to be *much* more permeable than the average bacteria (fun quote from the talk: "our theory is that these bacteria are permeable to everything except genomes"). Neither bacteria can synthesize a full set of amino acids; neither bacteria can live outside of the cicada's specialized cells; the cicada cannot survive without the full set of amino acids produced by the two symbionts. It's a fully-obligate three-way symbiosis, and it looks like Sulca and Hodgkinia are on their way to becoming cicada organelles. This makes Sulca and Hodgkinia potentially invaluable models of the early evolution of endosymbiotic organelles (mitochondria and chloroplasts, primarily). We can already see some of the expected genetic signatures -- Sulca and Hodgkinia have already lost key metabolic genes that are supplemented by the other species. Sulca is the relatively normal species of the pair. Hodgkinia has some wild stuff going on. For example, they're *missing key tRNA and tRNA synthetase genes*!!! That's absurd. Organisms basically can't produce any proteins without a full set of tRNA and tRNA synthetase... unless they're fed those molecules by a host. Hodgkinia apparently get by off of tRNAs produced either by the cicada or Sulca in the same cell (again, these cells are super permeable**). It goes a layer deeper, though. It turns out that Hodgkinia in many species of cicada have more than one form of genome, meaning that there are several (2 to possibly 80, depending on the species) different genome variants and each Hodgkinia cell has one of those variants (or, in some cases, two or three associated genome variants)***. Each genome variant has different deletions or pseudogenizations, but the population as a whole within each cicaca has complete coverage of the Hodgkinia genome. So in the two-genome case, there are some Hodgkinia that have deletions in one set of genes that are present in the other Hodgkinia, and vice versa. Somehow the cicada has to get at least some of every Hodgkinia variant (arguably, each Hodgkinia species, depending on how you want to define species here) from its mother, or it dies. We have no idea how the cicada ensures that it gets some of each. The point is that early endosymbiont evolution apparently isn't as simple as "they lose genes until they get to some sort of minimal set". Hodgkinia seems to be going through a weird *fragmenting* of its genome into overlapping and complementary populations. My suspicion is that the end product of this fragmentation will be consolidation into a single, minimal genome, which is what we see in many chloroplast and mitochondria... but even some mitochondria have multiple genomes! There's also a question of whether the genomic fragmentation of Hodgkinia is selectively advantageous, deleterious, or neutral. McCutcheon claims it's neutral, or possibly slightly deleterious, and I'm decently well convinced. Question to tuck away for later use -- could genomic fragmentation of this sort have been responsible for the development of eukaryotic chromosomes? * I also learned today that cicacas exclusively eat tree xylem sap, which is the sap that runs from the roots to the leaves. This is a terrible food source for several reasons. For one thing, it's really dilute for a nutrient-bearing liquid. For another thing, it mostly carries water, with just a bit of sugar. For another thing, it's under negative pressure, which means if you stick a straw into xylem, it will suck air into the tree rather than let sap out. To deal with this, cicadas need specialized mouthparts that actually suck liquid. In contrast, they *could* have fed on phloem sap, which runs from the leaves to the roots, and carries much more sugar and nitrogen, and is under positive pressure so that you just have to stick a mouthpart in it and it flows right out. I guess it just wasn't worth the extra difficulty of getting to the phloem sap... EXCEPT THAT PHLOEM IS CLOSER TO THE SURFACE THAN XYLEM IN MOST TREES. ** Maybe. That's the theory, at least. *** This took a bit of a heroic sequence assembly effort to figure out for the first time. One of McCutcheon's poor grad students tried sequencing the genome of a new cicada species, thinking rather reasonably that it would only have one. Nope. See the first two paragraphs of Results and Discussion here for details: http://ift.tt/1SyNjsz.

March 08, 2016 at 04:01AM

Today I Learned: 1) Addgene (and probably other companies) sells libraries of DNA parts in golden braid formats. The only catch is that they're almost certainly not compatible with libraries developed by other labs (including ours) so now there are at least several and possibly many non-compatible libraries siloed by their cut sites. So close, yet so far.... 2) ...a bit about the state of neuroscience from Dawna Bagherian I don't think I can summarize it better than her, so I quote: "I'm going [to a particular neuroscience talk] but I feel like I've heard this talk a thousand times. Every month someone has the revelation that cortical units don't necessarily encode one dimensional information and it's so surprising." Thanks Dawna Bagherian! 3) A tasty recipe: peanut butter, whey powder, honey, and oatmeal, in some reasonable amounts. Mix. Roll into balls. Eat or store for a while. Now to find a vegan substitute for whey powder.... Thanks to Suzannah Fraker for teaching me this!

March 06, 2016 at 09:13PM

Today I Learned: 1) There are anti-fouling paints for oceangoing ships that use capsaicin or chemical analogues to keep molluscs off. Clinging to a ship covered in hot sauce is apparently Not Very Fun. There's something odd about this, though -- why is it that capcaisin is painful to mammals and to molluscs but not to birds? Maybe it's a matter of delivery, so that if you rubbed capcaisin on a bird wound it would hurt just as much, but bird mouths don't absorb it? 2) I've heard wildly varying reports about the profitability of vaccines. On one hand, I've heard conspiratorial claims that companies make a lot of money off of vaccines, and are therefore trying to hide any evidence of deleterious effects of vaccination. On the other hand, I've heard that vaccines essentially don't make any money, and the companies that make them do so as a service more than a means of profit. Which is true? I'm not *completely* sure, but a little Googling suggests to me that it's... kind of both. First off, it seems that, for a number of reasons, vaccines have historically been wildly *un*profitable, particularly compared to drugs and other medical tech. The number of vaccine-producing companies has been shrinking since the 50s as companies have gotten out of the business, resulting in frequent vaccine shortages since the late 1990s. Source: http://ift.tt/16EogQd. However (and be aware that the following information is based off a single Atlantic secondary article (http://ift.tt/1TCF4Nm), making this paragraph one of the most poorly-researched paragraphs I've put out to date), vaccines have become a LOT more profitable since 2000, largely because of massively expanded access to vaccines in developing countries. So now there's a lot more money involved. 3) Wedding rings are not risk-free. According to a report by the Commission de la Sécurité des Consummateurs (http://ift.tt/1I1C865 WARNING: due to the nature of the report there's some highly disturbing imagery here) wedding rings are responsible for something like 300 cases per year over a roughly 60 million person population, which some quick estimates of mine (and some numbers off wiki) suggest is about TEN TIMES more than the rate of shark attacks in Australia. Most occur during everyday activity, and most cause serious damage requiring some form of microsurgery. Related, for all of you out there considering being doctors (*cough* Caroline Golino *cough*): http://ift.tt/1TCF2oJ

March 06, 2016 at 03:35AM

Today I Learned: 1) Apparently I've been cooking garlic wrong this whole time! 2) Tree rings are used to calibrate carbon dating. We know that a tree grows a new ring every year, so we can measure the carbon-14 fraction in different rings to calibrate how much decay to expect over different times (in woody tissues, at least). 3) For reasons I still don't entirely understand, flying at the speed of sound is much, much rougher and more unstable than either flying well below *or* well above the speed of sound. As a result, supersonic aircraft are designed to quickly accelerate through mach 1 to at least mach 1.05.

March 05, 2016 at 01:52AM

Today I Learned: 1) New trick for cooking with garlic -- instead of adding it to the pan as the last ingredient, just a minute or two before serving, add it as the *first* ingredient, cook it for about a minute (until it just starts to brown), take it out, and add it back at the end. Advantages: the garlic gets very well cooked through, and it... maybe adds some garlic flavor to the rest of the meal? Only tried this once so far, and it seemed to add a nice aftertaste. Need more sample size. Disadvantages: you have to pay close attention while the garlic cooks, which means it's hard to be preparing other ingredients in parallel. Also, taking out the garlic is messy, and there's some loss in whatever container you use to hold the garlic. Speaking of which, you end up having to wash whatever dish you hold the garlic in, which is one more thing to wash. Overall, I'm not entirely sold, but I may want to try it a few more times to get a better feel for the effect it has on flavor. Tip from Erik Jue! 2) There are purple fluorescent proteins. Of course there are purple fluorescent proteins. There's a purple fluorescent protein called mPlum. Of course it's called mPlum. 3) Primer design and primer overhang extension is a lot to teach someone who isn't an experienced biologist at once, if you expect them to immediately be able to apply that information.

March 03, 2016 at 10:56PM

March 03, 2016 at 02:35AM

Today I Learned: 1) The story of the competition race the Human Genome Project (HGP funded by NIH, making it a public project) and Celera (a private company run by Craig Venter) is quite fascinating, and it's a really fun story to pick sides on and argue about who "won". You can really go back and forth on it: HGP published the first assembled draft something like a few days before Celera, making it technically the first project to publish; but HGP had an eight-year head start on Celera, so Celera was really the spiritual victor (though it should be noted that even the public project finished under budget and two years ahead of schedule), especially because the public project draft wasn't particularly complete; but Celera was trying to essentially patent the important parts of the human genome and sell it, while HGP was going to make everything open access (and did, which massively accelerated research in many fields of biology), so HGP was the ethical victor; but Celera developed super-powerful sequencing techniques that totally revolutionized genomic sequencing (and which allowed HGP to finish on time...), *and* they completed the project for about a tenth the money as the public project, so Celera was clearly the technologic and scientific victor. Today I learned a new piece of the story. To explain this, I'll need to explain genomic assembly, which requires explaining shotgun sequencing, which is the technique invented by Celera and eventually adopted by HGP to finish the project. If you already know how shotgun sequencing works and what assembly is, you can skip the next three paragraphs. Before shotgun sequencing, there was Sanger sequencing. Sanger sequencing works like this: you amplify a stretch of DNA with PCR (a technique for producing lots of DNA from a targeted template sequence) but you also randomly incorporate special fluorescent versions of C, G, T, and A that terminate amplification. That gives you a bunch of fragments of the target DNA of different lengths, with a fluorescent nucleotide on the end of each. The color of the nucleotide depends on the letter at that nucleotide. You then run this mix on an gel, which separates the fragments by length. You look at the color of each band, and that tells you which nucleotide is at the end of the fragment of that length. You can read colors right down the line of bands. (technically that isn't *quite* how Sanger sequencing was done in the early days of the project, but it's close enough). The problem with this technique is that you have to know the sequence of the DNA at at least one end of the thing you're trying to sequence for the PCR to work, and preferably you should know both ends. This is a problem when the whole point is to figure out what the sequence of the DNA is. What the HGP did was to sequence from some known bit of the human genome, then use the new sequence to amplify the next bit, then the next bit, and a few hundred nucleotides at a time they could eventually sequence it all. Shotgun sequencing uses the same idea, except that before the Sanger reaction to add fluorescent nucleotides, you shear the DNA you want to sequence in to bazillions of little fragments of a few hundred bases each, which you can then clone into a ton of plasmids. You amplify each plasmid in bacteria, then sequence the plasmid. Since you know the sequence of most of the plasmid, it's trivial to amplify. This way, you don't have to bootstrap your way through the genome -- you can just sequence thousands or millions of fragments at once. Combined with new machines for performing the sequencing reactions more efficiently, shotgun sequencing allowed Celera to churn through the genome ridiculously faster than the HGP could with Sanger sequencing. There's a bit of a catch, though. With Sanger sequencing, you get a bunch of slightly overlapping sequences, in order, which you can easily string together into a whole genome. With shotgun sequencing, you get millions of *randomly selected* fragments, with no information about where they came from other than "somewhere in the genome". With enough random fragments, you can find overlapping fragments and stitch them together into entire chromosomes... but that's a computationally difficult puzzle to solve. This is the problem of assembly. This is where UCSC comes in (that's the University of California Santa Cruz). David Haussler, a professor at UCSC, was tasked with assembling the fragments from the public genome project. I think there were others involved, but Haussler is the only one I know of, and he ended up being the most critical. Anyway, one of Haussler's graduate student, an industrious fellow named Jim Kent, was particularly interested in the assembly project and came up with an assembly algorithm, then wrote up an assembler in about four weeks of intense coding. During that time, he also wrote the world's first interactive web-based genome browser, which was released with the public genome project draft as the UCSC Genome Browser, probably the most popular single tool in the world for retrieving data about the human genome (with the possible exception of BLAST?). Kent and Haussler deployed the assembler on a hastily-assembled cluster of about 100 Pentium III desktops. Now, this was 2000, and Pentium IIIs weren't as laughable as they are now, but for reference consider that a typical Pentium III is slower and less powerful than your average cell phone processor today. Admittedly, there were 100 of them... but Celera was using rather more powerful computers, better optimized for the kind of string comparisons required for assembly, and they had THOUSANDS of them. Haussler and Kent released their first assembled genome three days before Celera. 2) DNA sequences, espeically for populations are really more naturally viewed as graphs than as strings. The standard way to represent a DNA sequence (say, the human genome) and its variants (say, YOUR genome in all of its quirky variation) is to have a canonical reference sequence against which you align all sequences, and individual variants are noted against the reference. For humans, there is one public reference genome, which is now on its 38th version, against which all human genome assembly is performed. If you were to get sequenced, your genome would be mapped against this reference, and you would essentially get a list of differences between your genome and the reference. Instead, you can think of a set of sequences as a graph of connected short sequences. This is way easier to explain with pictures, but I run a text-only TIL, gosh darnit, so here goes. Consider these four example genomes of a very, very small organism: 1) ATTGTTTTGCGCA 2) ATTCTTATGCGCA 3) ATTGTTTTGCGCA 4) ATTCTTCCCCCTTGCGCA The traditional way to think about these genomes would be to build a "consensus sequence" that best represents the common elements of all of them, which would probably be "ATTGTTTTGCGCA". Genomes 1 and 3 are exactly the reference sequence; genome 2 has a mutation in the 7th nucleotide; genome 4 has an insertion "CCCCC" in between the 7th and 8th nucleotides. Alternatively, you could represent these sequences collectively as a graph where each node is a short sequence and directed edges between nodes means "that sequence follows this one" with a weight proportional to the frequency at which those two sequences go together. So the graph would start with the node "ATTGTT"; that node would point to each of the nodes "T", "A", and "CCCCC", with weights of 2, 1, and 1, respectively; and each of those nodes would point to the sequence "GCGCA". If you trace any path through the graph from beginning to end, it spells out a sequence. You do lose some information in this representation, like which mutations are associated with which other mutations, but there are advantages too. For one thing, it's a natural way to visualize the variation within a population. It's also helpful for assembly -- any variations from the reference sequence mess up the assembly process, but using a graph representation, you know what the most common variations are and can account for them. The graph representation also gives you a clear idea of what the most variable regions of the genome are, and which ones tend to stay constant. 3) A liquid biopsy is when you take blood from a cancer patient, filter out all the cells, and sequence all of the bits of DNA you can find floating around. It's not a very efficient way of sequencing a cancer, but it *is* highly uninvasive and easy to perform, and apparently there's usually enough cancer DNA floating around to get a good idea of what cancer it is.

March 02, 2016 at 02:40AM

Today I Learned: 1) Unstructured proteins are not the same as denatured proteins. The term "unstructured protein" is a rather glaring misnomer. Unstructured proteins almost always have structure, and well-defined structure at that. The "unstructured" tag just means that they aren't made of standard protein building blocks like alpha helixes and beta sheets. One way to think of it is that if anyone but an experienced protein scientist/engineer looked at a snapshot of an unstructured protein, they wouldn't be able to tell whether or not it was denatured, because it wouldn't have any of the usual protein structural features, BUT if you looked at a million copies of that protein, it would always look more or less the same. A "denatured protein", on the other hand, truly isn't structured. Denatured proteins flop all over the place; if you looked a million copies of the same denatured protein, they would all have different shapes. Thanks to Jeanne Morin-Leisk for teaching me about unstructured/denatured proteins! 2) When inserting DNA into plasmid vectors, it's a good idea to run a control reaction that doesn't insert anything. This screens for whole, uncut plasmids contaminating your vector -- if your control transformation has a lot of colonies, that means you can expect a lot of your actual transformations to be uncut vector, not your actual construct. If you have just as many control colonies as experimental ones, then you probably don't have any good colonies and you don't need to bother screening. A caveat: Gibson reactions tend to produce a lot of colonies in control reactions, even when the main reactions work just fine. ...I realize that the above paragraph won't mean much if you haven't done cloning before. For those of you, the tldnr is: today I learned a potentially useful control condition to use when performing certain common cloning reactions. Also, to be clear, here and in the rest of molecular biology, "cloning" just means "making DNA from other pieces of DNA", and has nothing to do with copying organisms. 3) Mimiviruses! Mimiviruses are MASSIVE viruses that infect amoeba*. How massive? Well, they were thought to be bacteria for a long time, because they kind of look like bacteria under a microscope (they're between 400 and 600 nanometers across, depending on how you measure, which is about half the length of a typical E. coli cell). Mimiviruses (obligatory: mimiviri?) also have a LOT of DNA -- the mimivirus genome is more than a megabase, encoding almost 1,000 genes, which is significantly larger than some bacteria (though still smaller than most, to my knowledge). More interestingly yet, mimiviruses carry several genes for amino acid and nucleotide synthesis, making them significantly more self-sufficient than your average virus and arguably more self-sufficient than some parasitic bacteria (I'm guessing mimiviruses can replciate their own DNA, but they definitely don't have their own ribosomes, so they can't produce proteins on their own). Mimiviruses are a contentious topic among scientists-that-know-about-mimiviruses. There's a lot of question about how mimiviruses came to be -- are they descended from parasitic bacteria that gradually lost their cytoplasm and cell walls, developing protein coats in their place? Or are they viruses that incrementally incorporated host genes for metabolism to gain more and more functionality? Or was it a virus that independently evolved genes for metabolism? Some scientists even been claim that mimiviruses, along with other closely-related viruses, meet criteria for life** and should be considered a fourth domain of life alongside prokarya, eukarya, and archaea. Questions about evolutionary origins like this are very difficult to answer (as Mengsha Gong can attest!), and we will likely never definitively know how mimivirus came to be. * Appropriately enough -- things related to amoeba seem to have a weird habit of being disproportionately large. Check out Chaos carolinense. Also, how big do you think a typical amoeba's genome is? For reference, a human genome is ~6,000,000 base pairs, bacterial genomes range from a couple hundred thousand base pairs to tens of millions of bases, and flu viruses have about 14,000 base pairs. Take a guess. Now go look up the genomes of Amoeba dubia and Amoeba proteus (for those without the ability to look it up, my apologies, but this really is a better exercise if you have to look it up yourself than if I post the answer). ** Personally, I think *all* viruses should be considered "alive", but that's a personal crusade of mine and it's not like it matters anyway.

Edit:  A couple more things I learned yesterday but forgot to write down:

1) Mimiviruses have their own viruses. That's not the first virus-infecting virus I've heard of -- adeno-associated viruses, or AAVs, are human adenovirus parasites that only infect human cells also infected by adenoviruses. AAVs are among the most popular vectors for viral gene therapy right now, in part because they can't replicate on their own. I also learned that a virus that requires another virus is called a "viriophage", which roughly translates to "virus eater". 

2) It looks like mimiviruses have an immune system against their viriophages, which probably acts much like the CRISPR system of bacteria that has given us Cas9, which I've written about at some length in other posts. Seehttp://www.nature.com/.../crispr-like-immune-system..., if it's not behind a paywall.