Note (12/2015): Hi there! I'm taking some time off here to focus on other projects for a bit. As of October 2016, those other projects include a science book series for kids titled Things That Make You Go Yuck! -- available at Barnes and Noble, Amazon and (hopefully) a bookstore near you!

Co-author Jenn Dlugos and I are also doing some extremely ridiculous things over at Drinkstorm Studios, including our award-winning webseries, Magicland.

There are also a full 100 posts right here in the archives, and feel free to drop me a line at secondhandscience@gmail.com with comments, suggestions or wacky cold fusion ideas. Cheers!

Homeobox


· Categories: Biology, Genetics
What I’ve Learned:

Homeobox: when it comes to transcriptional regulation, it's not clowning around.
Homeobox: when it comes to transcriptional regulation, it’s not clowning around.

A lot of my confusion about science isn’t really my fault. For instance, when I was in college, In Living Color was on Sunday nights, and a must-watch every week.

So when I stumbled into genetics class at ass-early Monday morning, I still had Homey D. Clown on the brain. Can I be blamed for thinking “Homey O’Box” was Clown’s Irish cousin? It’s a mistake anyone could make, if they were a fan of sketch comedy. And it was before nine AM. And they weren’t very bright.

Eventually I learned that a homeobox isn’t a clown, but a conserved DNA sequence. With very little variation, you can find the 180-base pair stretch in the genomes of most every eukaryotic species, from single-celled fungi to duck-billed platypi all the way up to humans. Including clowns.

When a homeobox gene is expressed, the 180-base stretch translates into a 60-amino acid structure in the resulting protein. Those amino acids form a three-helix structure, which is just the right shape to hook onto the double-helix structure of DNA. So the proteins containing this structure, called homeodomain proteins, are able to bind directly to DNA, which comes in very handy.

That’s because binding to DNA near a gene is a good start to controlling whether or not that gene gets translated into proteins. Some homeodomain proteins, like those in the Hox family, are “master regulators” of transcription, turning genes on and off like an old-timey switchboard operator. This regulation can be triggered in all sorts of ways, but it’s especially important during early development.

As an example, consider the fruit fly — where the homeobox sequence was first identified, back in the 1980s. Scientists found a bunch of Hox-family homeobox genes in flies, and discovered that when one or more of them were mutated, the flies grew in wild and freaky ways. Scramble one gene, and the flies made four wings instead of two. Hork up another, and they grow mouths on the outside of their face, rather than the inside. And a famous Hox mutation makes flies grow legs on their heads, where the antennae should be.

This may be similar to a mutation I assume Abe Vigoda has, which caused him to grow woolly caterpillars where his eyebrows should have been.

Homeobox genes appear to have been with us for a very long time — since before there was an “us”, in fact. They’re found in organisms as simple as yeast and sea anemones, suggesting that the homeobox sequence first evolved in some ancestor common to all the species where it’s seen today; that ancestor would be around 600 million years old, or way before humans made the party. Or clowns. Hell, even Abe Vigoda might not have been born yet.

There’s also a chance we swiped our homeobox tricks from some ancient pre-dinosaur Cryogenian-era virus. No modern bacteria or simpler species have homeobox genes themselves, but one bacterial virus called lambda phage does have DNA-binding proteins that look an awful lot like homeobox genes. So maybe some prehistoric proto-sponge yoinked this precious and valuable sequence that every animal, plant and fungus relies on today.

Now that sounds like a heist worthy of Homey O’Box. Maybe Homey do play that, after all.

Actual Science:
Genetics Home Reference – Homeobox gene family
The Embryo Project Encyclopedia – Homeobox genes and the homeobox
PLoS Blogs – When an arm is really a leg
Science Daily – Gene for dissected leaves: lost gene leads to simple leaves
Medical XPress – A master gene determines whether cells become pancreatic or liver cells

Image sources: StudyBlue, Genius.com (Homey, not playing that), People in White Coats (antenna-people-pedia), Roscoe Reports (Abe’s bushy brows)

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Nude Mouse


· Categories: Biology
What I’ve Learned:

Nude mouse: Taking it ALL off for science.
“Nude mouse: Taking it ALL off for science.”

This being the internet, you might think “nude mouse” is the title of a Mickey and Minnie fan erotica script.

And probably it is. Rule 34, after all.

But for biologists — regardless of any disturbing Disney peccadilloes they might harbor — a nude mouse is something else, and something tremendously useful for research. Nude mice have genetic mutations in the FOXN1 gene, an important transcription factor highly conserved among mice, rats and humans, among others.

Knocking out FOXN1 function has two main effects. First, it prevents the proper growth of hair and nails. That’s the “nude” part of “nude mouse”, as FOXN1-deficient mice are a bunch of hairless, wrinkly pink monstrosities. It’s like watching a four-legged horde of that old guy from the Six Flags commercials a while back. Only with less dancing, probably.

That’s because the other effect of disrupting FOXN1 is an underdeveloped or absent thymus. The thymus is the organ where T cells develop, so missing a thymus leaves a nude mouse severely immunodeficient. They’re susceptible to virus infections and tumors, can’t mount cell-mediated immune responses and are unable to reject transplanted tissues.

That’s no picnic, if you’re a nude mouse. But if you’re a researcher studying infections diseases, cancer, immunodeficiency or treatment of human cells in an animal model, then it’s pretty sweet. Nude mice have been used extensively in studies using xenografts, or tissue from one species implanted into another. Human tumor cells, for instance, might be xenotransplanted into a nude mouse, which is then treated with an anti-cancer compound to see how well it works in a live animal.

Which is to say, a live nude animal. Sexay.

The first naturally-occurring nude mouse was discovered in the 1960s. I assume it was easy to spot back then, as it would have been the only lab mouse without an afro. Because there are many possible mutations that can disrupt FOXN1, several distinct strains of nude mouse have been described.

(Described as “wrinkly little E.T.-looking freaks”, I imagine. But still.)

Most nude mouse strains are “leaky”, which is significantly less icky than it sounds. Here, it just means that the mice retain some thymic function, and often low levels of T cells. Because we humans think we always know the best way to do everything, we’ve now developed knockout mice, where genes important for T cell development are completely scrambled, and there’s no pesky leaking.

So the nude mouse isn’t used as often these days in lab research, but these bald mutant rodents have helped make breakthroughs in immunology, oncology, parasitology, pharmaceutical research and more.

But NOT Disney-inspired fan erotica. Get those minds out of the gutter, people.

Actual Science:
Christus Stehlin – Nude mice
Nature – Regenerative medicine repairs mice from top to toe
AnimalResearch.info – Mouse (immunodeficient)
Science Daily – The nude mouse tale: omega-3 fats save the life of a terminal cancer patient

Image sources: Scanbur Research (nude mouse), Left Wing Libertarian (Mickey and Minnie, bow-chicka-mouse-mouse), Reddit (Six Flags guy gang), Pinterest (He’s a bad mutha mouse… Shaft!)

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Junk DNA


· Categories: Biology, Genetics
What I’ve Learned:

Junk DNA: there's a whole lotta junk in ALL of our trunks.
“Junk DNA: there’s a whole lotta junk in ALL of our trunks.”

Comparing yourself with other people is tricky. George Carlin famously pointed out that “their stuff is shit, but your shit is stuff“. Which is great, if you’re comparing music collections or wardrobes or childrens’ refrigerator art.

But there’s another thing we have in common with other people: our DNA. And when it comes to genetic material, it turns out everybody’s is mostly junk. Yes, even yours. And George Carlin’s.

(Well, at this point, certainly George Carlin’s. Unless you count half of Kelly Carlin. Which you probably should.)

But don’t feel too bad about your junky genome. “You are what you eat,” as the saying goes — so if you’ve ever shoveled down a McRib or a whole bag of powdered mini donuts down your gullet, then you knew some “junk” was probably in there, somewhere.

The question is… how much? No one is entirely sure.

Regrettable food choices aside, the degree of “junkitude” in a species’ DNA was first measured in a very simple way. Somewhere within that DNA are a number of genes — regions that are transcribed into RNA messages, and then translated into proteins, which perform most every function in living cells.

Different species have different sized genomes, and varying numbers of genes. Back in the ’60s or so, scientists took a hard line concerning “junk DNA”: if it can produce a protein, it’s useful. If not? Junk.

That leaves many species with an awful lot of so-called junk DNA — and it makes humans look like downright hoarders. Using this definition, roughly 98% of our DNA is pointless garbage. Expired Fruitopia coupons. Porky’s Revenge Betamax tapes. Last year’s newspapers. Or really, any newspapers.

But a funny thing happened on the way to our deoxyribonucleic intervention. As scientists dug deeper into how our genomes work, they discovered something interesting. Our non-protein-coding DNA may be “junk” — but that junk DNA… is not.

Not junk, that is. At least, some of it isn’t. Because while genes — actual, protein-producing sequences — only make up about 2% of our DNA, other regions are pretty important, too. Like telomeres, for instance — little fiddly bits of DNA that “cap” chromosomes to protect the squishy ends. Or for that matter, centromeres — repetitive sequences where two halves of each chromosome are held together, and which are critical during cell division.

But it’s not just structural elements hiding in the junk DNA. There’s other stuff in that shit, too. Thousands of regulatory sites, for instance. All those protein-encoding genes are great — but on their own, they’re kind of dumb. If you don’t want intestine genes turned on in your brain, or adrenaline released along with melatonin — and seriously, you do not — then something has to regulate how and when and where and why each gene gets expressed.

That “something” is a bunch of proteins, mostly — but they do their jobs by sitting down on stretches of non-coding DNA to direct traffic. Take away those “junk” DNA regions, and your gene expression suddenly goes all higgledy-piggledy. Congratulations, spring cleaner. You’re a sewer mutant now.

There are other important things happening in our “junk” DNA, but we’re still discovering what all of them are. Maybe 10% of our DNA is actually useful. Or 8.2%, according to one study. Maybe as much as 50%. But probably not more than that; nearly half our DNA is thought to come from transposable elements and integrated viruses, which are generally not so useful.

So Carlin wasn’t wrong, but he didn’t have the whole story. True, our shit is stuff, and their stuff is shit. But underneath, we’re all 50 to 98% junk. Sorta makes you want to mutter the seven words you can never say on television, dunnit?

Actual Science:
Scientific American – Hidden treasures in junk DNA
Live Science – People use just 8.2% of their DNA, study finds
io9 – What extraordinarily weird things are locked up in your junk DNA?
Quanta – A surprise source of life’s code
Scitable / Nature Magazine – Transposons, or jumping genes: not junk DNA?

Image sources: Biotechnology and Society (junk DNA), Amazing Spaces (Carlin, finding a place for his stuff), YouTube (powdered donut face), Daily Beast (sewer muties, wavin’)

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Quiescence


· Categories: Biology
What I’ve Learned:

Quiescence: how much less growth could there be? None. None less growth.
Quiescence: how much less growth could there be? None. None less growth.

Isaac Newton said a body at rest tends to stay at rest. That’s the First Law of Motion.

My mother said a body at rest had better tend to get his lazy teenage ass off the couch and mow the lawn before his father gets home, if he knows what’s good for him. I’m not sure that’s a “law” of anything, but it always got me moving. Eventually.

Inside your body are trillions of cells, and right now many of those are also at rest, in a state known as quiescence. What they tend to do next depends on what sort of cells they are, and how they got into that state to begin with.

Like teenagers, most cells go through phases. But instead of “goth skateboarder” or “sparkly vampire”, your cells go through phases of the cell cycle. The cell cycle is a set of steps cells go through to divide, because reproducing requires very careful planning.

If a cell went through the division process without a roadmap, anything could happen. It could split before it’s ready, and produce deflated Whoopie cushion cells that aren’t helping anyone. It could get its DNA scrambled, and serve it to the daughter cells, family-style. Or it could divide into fourteen cells at once, none quite the way they should be. Like Duggars. It’s terrifying. Thank goodness for the cell cycle.

But a cell’s life isn’t all spent thinking about reproducing. This isn’t college. Sometimes, cells need to exit the rat race of dividing over and over, and rest in quiescence. Take heart muscle cells, for instance. Once your heart has grown to full size during development, you don’t want it getting any larger.

(I know people like to think they have a “big heart”. But if it were big enough to squish your lungs between your ribs, you might reconsider that goal.)

To keep your heart from growing three sizes each day, the mature muscle cells are pulled out of the cell cycle right after a division, in a phase called G1. The “G” stands for “growth”, which is what cells typically do after dividing, but quiescence is a resting state, sometimes called phase G0. Because there’s no growth. Or dividing. Or anything else. The cells just sit there, doing their thing. Pumping blood, keeping you alive and leaving all the worrying about reproducing to you. If you’re into that kind of thing.

This also happens with neurons and other cells that stop growing after development; they enter quiescence, and basically never come out. But other cells can slip into the G0 phase from G1, for just a little post-division breather. Think of it as microscopic maternity leave.

Except that once cells divide, there’s no “parent” cell left. So really, it’s the children who were just produced that get a rest. Lazy kids. That grass is never getting mowed.

These “paused” cells — and in theory, any cells — can be pulled out of quiescence under the right set of circumstances. That could be a growth factor released in the body, or some other growth-goosing signal. Or maybe there are little mothers running through our bloodstreams, telling cells to get busy and do their chores.

The textbooks are silent on that last one. But sometimes, it’s the only thing that works. You do not want to be in the quiescence phase when your father gets home.

Actual Science:
Boundless – The cell cycle and the G0 phase
BioMed Central – Proliferation/quiescence: the controversial “aller-retour”
Stanford Medicine – On alert: study identifies cell-cycle phase that primes stem cells for action
Jackson Laboratory – Forcing quiescent leukemia cells to proliferate holds promise for acute myeloid leukemia (AML) chemotherapies
Medscape – Diabetes drug appears to eliminate residual CML

Image sources: University of Texas (cell cycle circle), Unilad (lazy, lazy teen), Mom This Mom That (Grinchy heart growth), Life as a Divorced Dad (quiescent kid, uncut grass)

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Immunoglobulin


· Categories: Biology
What I’ve Learned:

Immunoglobulin: even your immune system has door greeters.
Immunoglobulin: even your immune system has door greeters.

I took an immunology class back in college. I’m not sure why, exactly — maybe I thought it said “immortality” and I was looking for the secret to eternal life.

What? I went through a Highlander phase. We’ve all been there.

Anyway, it quickly became clear this class was something completely different — and completely hard. Everything about immunology is complicated as hell. There are, like, nine hundred different kinds of immune cells, a billion marker proteins and pathways out the wazoo. Stuff gets activated. Things turn into other things. Some cells remember crap, some cells spread the word about crap, other cells kill crap… it’s exhausting.

Then they told us about immuno-goblins. And finally, something made perfect sense. It was a couple of months into the semester, the middle of October just like now. Halloween was looming, so goblins were on everyone’s mind.

So when the professor explained these immunogoblins are produced in enormous hordes within the body, each on the lookout for a specific interloper, it made sense. When she told us each immunogoblin’s individual characteristics comes from mutations… well, duh. And when she said they either neutralize invaders or mark them for others to overwhelm — yeah, that sounds exactly like a bunch of goblins.

I went into that test full of answers. Basically, my body is Mordor. It pumps out goblins by the billions, looking out for viruses and bacteria and, I don’t know, effeminate ring-bearing halflings? I didn’t really study for those Tolkien exams, either.

Long story short, I got a 12% on the test, failed the class and apparently there’s not a little tiny Saruman living inside of me, releasing hordes of goblins.

(Turns out it was heartburn. Booo-ring.)

But all that stuff about immunogoblins — sorry, I was informed in red ink those are “immunoglobulins” — is apparently true. These are proteins produced by our immune cells in huge numbers, with millions of different kinds. The tips of each protein contain regions called paratropes, shaped to specifically recognize one specific antigen. Like an elbow of an influenza virus, or a tuberculosis pinky toe.

Binding of an immunoglobulin to its antigen may take the baddie out of commission. But just in case, it also triggers the immunoglobulin to signal to the rest of the immune system to get its ass in gear and come help.

That’s less of a “goblin” thing that immunoglobulins do, I guess. It’s more like a Wal-Mart greeter. Assuming the Wal-Mart was staffed by sentient killer cells ready to surround you, break you in half and eat you. Which, as I understand it, is most Wal-Marts.

In the end, I did learn a couple of things about immunoglobulins. So if you’re ever stuck staring down an immunology exam, just remember these three things:

1. When an immunoglobulin is glommed onto an immune cell, it’s just called an immunoglobulin. But when it’s farted out into the bloodstream to look for victims, it’s called an “antibody”. Personally, I would have gone with “Globs the Bounty Hunters”. This is probably why no one ever asks me to name things.

2. That “paratrope” bit that makes immunoglobulins unique has nothing to do with paratroopers, even if you have an awesome story about your great-grandfather dropping into occupied France to storm… uh, Nazi baguette bunkers or whatever. History was also not a thing I was good at.

3. Immunoglobulins are not like goblins, which means your body is also (probably) not like Mordor. Instead, they’re like evil greeters, which makes your body a Wal-Mart built on a hellmouth. Which seems redundant, and also mostly the same as Mordor, but I’m not the one grading these tests, so give the professors what they want, I guess.

Like I said: immunology is complicated.

Actual Science:
WebMD – Immunoglobulins
Study.com – The five classes of antibodies
University of Arizona – Immunology problem set
The Biochemistry Questions Site – Immunoglobulins: structure and functions
Science Clarified – Antibody and antigen

Image sources: MedGadget (immunoglobulins), Wikia (Tolkien goblins), Pop Cult Assault (beware, Dog), Walmart Wall (terrifyingly friendly greeter)

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