Thursday, February 5, 2015

Promised post about telomeres!

In light of a recent (and very exciting) study about the transient activation of telomerase for elongating telomeres and easing age-related diseases, here is the lay-man's background for why the study is exciting. At least I'm going to try to make it lay-friendly. I have visual aids and everything.

For these purposes, I'm going to assume everyone knows what DNA is and what we (as living things) use it for. If you don't know those things... Wikipedia, people. However, since this is getting into some fairly heavy molecular genetics, something I'm pretty geeky about, I might ramble off down some obscure bio-geeky rabbit-hole. If that happens, just whack me on the head (preferably in the comments).

Ok, first things first. Telomeres are important because of the role they play in DNA replication, so we're gonna talk about that real quick. Whenever a cell divides, it's got to duplicate all its bits, including the DNA that carries the instructions for all those bits. It does this in a very specific way (and every single organism on the planet does it the exact same way) in order to ensure the accuracy of the copies. DNA is a double-helix, which means it's two strands that are twisted around each other. The entire strand (humans have 23 separate strands) is tightly coiled together to make a rod-shaped structure called a chromosome. To make a copy, the two strands unzip and cellular machinery copies each strand. This allows each parent strand to serve as a template for the new one. It forms two 'daughter' double-helices that each contain one strand from the parent helix and one brand-new strand (semi-conservative).  Once the whole chromosome is copied, the two helices are still connected at the middle, forming the X-shaped structure that's characteristic of chromosomes during cell division. That's DNA replication in a nutshell.

Each strand of DNA is directional, meaning it has a 'front' end and a 'back' end (or right and left, if that's easier) that are molecularly distinct from one another. The two strands in the double-helix line up front-to-back (anti-parallel). The backbone of each strand is made up of ribose sugars, the carbon atoms in which are numbered. The ends of the strands are named for the carbon atom that is sticking out: 3' or 5' (3-prime or 5-prime). For our purposes, let's call the 3' end the front and the 5' end the back.

The DNA replication machinery (a protein called DNA polymerase) only moves one direction: 3' to 5', or front to back. If the whole DNA molecule would just open up, the machinery could just start at each 3' end and zip on down. Unfortunately, single-stranded DNA is very unstable and the cell's own defenses attack and destroy it immediately. So, the DNA only unzips the tiny portion where the machinery is actually working. This means that one side will still get to just zip on down, but the other side will have to be a bit more clever. The strand that can replicate in the 'right' direction is called the leading strand and is, for our purposes, uninteresting. The side that is having to replicate in the 'wrong' direction is the one causing all the problems. The machinery can still only copy in a front-to-back direction, so replication occurs in short fragments (in the right direction) that are later glued together. A kind of leap-frog motion allows a small fragment to be copied, the machinery to hop backward and begin again behind the fragment it just created as a new area of the double-helix is unzipped. The spots where the machinery re-binds are marked by little pieces of RNA binding to the DNA (called primers). Another machine comes in later to replace the little RNA primers with DNA... but this can only happen if there is DNA on either side of the RNA primer. This isn't a problem until it gets to the very end. Because there isn't any DNA on the other side of the very last spot the machinery needs to bind, that RNA primer can't be replaced with DNA, so it eventually falls off, leaving a small piece of single-stranded DNA exposed. Remember what I said about the cell really not liking single-stranded DNA hanging around? The cell's defenses come in and chop off that little piece of DNA and dispose of it.

BUT HANG ON A SECOND. Our chromosome just got 20 bases shorter! Isn't that stuff important? Don't we need that? That happens every single time the cell divides?!

I'm so glad you asked.

This is what biologists refer to as the 'end replication problem'. This is where telomeres come in.

Telomeres are long sections of repetitive DNA (in mammals, it's a bunch of repeats of TTAGGG) at the ends of the chromosomes that don't contain any genes. Their sole purpose is to protect the important stuff (the genes) from replication-induced degradation. So, the replication machinery copies the DNA all the way down the chromosome, and all the way to the end of the telomere. When that small piece of single-stranded DNA gets cut off, it's the non-coding telomeric repeats that get chopped and not the important stuff. It serves as a buffer, like the plastic cap on the end of a shoelace. As a side benefit, the repetitive nature of telomeres also makes them curl up, which protects the ends from over-zealous cellular vigilantes that fix double-strand breaks by fusing chromosomes together. The centromere is another area of non-coding, repetitive DNA that serves a mechanic purpose and not an instructional one. It allows the chromosomes to be pulled apart during cell division.

So. The telomeres get a little shorter every time the cell divides. There does come a time when the telomere gets 'used up'. Usually at this point the cell stops dividing. Depending on its genetic history and cell type, it may enter a state of senescence (it keeps on doing its thing, but doesn't divide), or it may commit suicide (known as apoptosis or programmed cell death). When a lot of cells in the body get to this stage, as you may guess, the body itself isn't looking so good. Many of the ailments of old age can be attributed to shortened telomeres and the resulting decrease in cell division. Cells divide for lots of reasons, the most prominent being to repair damage (injury) and to mount an immune response (illness). With decreased cell division, an organism doesn't heal from injury as quickly and is more susceptible to infection. As undesirable as these things are, they're just a result of 'normal' wear and tear. However, sometimes when the telomeres are exhausted, the cell doesn't stop dividing. It begins chopping off ends of important genes and those genes now code for faulty or non-functional proteins. DNA damage like this has been linked to several forms of cancer typically associated with old age.

BUT. If the telomeres get shorter every time a cell divides, aren't we passing on progressively shorter and shorter telomeres to our offspring? Why haven't we died out yet??

Good question. We aren't, which is why we haven't. There is a protein called telomerase that builds the telomeres back up. It's active in stem cells during early development, so we can get from a fertilized egg to a multi-cellular person without losing a bunch of our telomeres. It's also active in... you guessed it! Gametes. Sperm and eggs. So rest assured, you're equipping your kids with a full set of telomeres.

So, why can't we just turn telomerase back on and keep those cells dividing without damaging the DNA? Fountain of youth, right here! I feel a Nobel Prize coming on...

Because unregulated telomerase activity basically turns cells immortal... and we have a word for immortal cells: Cancer. The other major place where telomerase is active is within tumor cells... 90% of cancers have active telomerase. A cancer is basically just a group of cells that have lost all their inhibitions and continually divide. The normal mechanisms that tell cells to stop dividing because we have enough lung for now, thanks have either been permanently switched off or damaged. Tumors are just areas of unrestrained cell growth.

So yes, telomerase has some pretty powerful implications for the ageing process and its associated discomforts... but our cells keep it on a short leash for a very good reason.

Ok, so now you're ready for the article. It's here.

In a nutshell, cells were treated with a small piece of messenger RNA (the RNA that transcribes DNA genes and takes the info out of the nucleus so it can be made into a protein) that codes for the 'active ingredient' in telomerase (telomere extension reverse transcriptase, or TERT). The new and awesome part of this procedure is that it's transient. Remember what unrestrained telomerase does? Bad stuff. So, here, they've restrained it. The RNA 'signal' only persists in the cell for about 48 hours. Then it's gone and the telomeres (newly lengthened) begin to shorten again like normal. Fortunately, the researchers think that the procedure would reverse telomere shortening equivalent to about 10 years in humans. This means that any treatments developed from this procedure could be administered less frequently than a tetanus booster. 

This new transient application of TERT would reduce the risk of cancer resulting from treatments like this, and the need for repeated treatments doesn't seem prohibitive. Therapies could be generalized to treat general old age symptoms or very specific to treat diseases associated with age (like diabetes and heart disease) and prematurely shortened telomeres (like progeria, liver pulmonary fibrosis and liver cirrhosis).

Pretty cool, huh?

Tuesday, September 9, 2014

Bird species ranges are shifting en-masse


It's waaaay too much hassle to actually cross-post, so I'm just going to link to the Bander-and-Barista post. It's here.

Wednesday, September 3, 2014

A rant about the state of the internet

In the aftermath of the hacked and leaked nude photographs of the multiple celebrities (mostly young and female), I feel the need to add my voice to the ever-growing chorus.

Taking advantage of a tragedy to make a point? OF COURSE I AM. What better time to talk about and emphasize the importance of smoke detectors than in the aftermath of a rash of house fires? What better time to talk about gun control laws than in the aftermath of a crazy guy with an assault rifle shooting up a movie theater? Why? Because humans have a very short collective attention span. This incident will hold America's collective attention for awhile because there were famous boobs involved.

The slut-shaming and victim-blaming have got to stop. Slut-shaming and victim-blaming, in general, need to stop... and this unfortunate incident has the bright silver lining of bringing up that point once again. This whole greasy stain on the fabric of decency comes down to two issues and two issues only.

Issue #1: Consent.

Issue #2: Female bodies, sexuality, and expression as public property.

Various news and blog articles have covered each of these issues in the last few days, but I wanted to touch on both of them in their larger societal contexts as well.

Consent.

In its most black-and-white form, most decent 21st century humans agree on this point. In a sexual context, if someone (male or female) says "no" and then fights back, there is a problem, and in a court, those two actions clearly show that the act was non-consensual. But what if the victim is unable to say "no" or fight back? Intoxication, unconsciousness, or even paralyzing fear will cause one or both of these obvious consent-revoking actions to be absent. What about a victim wanting to say "no" and fight back, but being unwilling to do so for fear of reprisal by a violent and physically overpowering assailant? An attack that began as a rape ends in murder often enough for this to be an understandable response. The concept of 'asking for it' is dangerous and insidious. Provocative attire, walking alone at night, even intoxication and drug use are on a long list of behaviors that do not indicate or replace consent. Even if consent is given initially, it can be revoked at any time. Period. Another area where consent can be revoked at any time is within the implied consent of a long-term sexual relationship (such as a marriage).

Consent is everything. It changes the exact same behaviors from welcome intimacy to traumatizing assault. The fact that the average human male can easily physically overpower the average human female is what makes this so important. "With great power comes great responsibility," says Spiderman's uncle. It doesn't just apply to mutant spider-bite superpowers, guys. All of this comes down to the sexual education of our young. We need to better teach girls to stand up for themselves and say "no", but we also need to teach boys how to accept "no". We try to teach our girls how to not be raped, but we haven't we taught our boys how not to be rapists.

So what does this have to do with some douche-bag leaking naked pictures of celebrities to all-and-sundry on the internet? Everything.

It's similar to the disturbing trend of 'revenge porn', except that this was done by a random stranger with hacking skills instead of an angry ex-lover with a grudge. As with revenge porn (when someone posts explicit or intimate photos of an ex on the internet without the ex's consent), photos like these are almost always taken with permission and freely given within the context of a loving relationship. Everything is fine. There are no sluts here. There is no 'asking for it'. Sharing these intimate aspects of a relationship with the great wide internet after the relationship ends (even if it ended badly) was not consented to, and is therefore as much sexual assault as rape. 'The Newsroom' (an Aaron Sorkin drama on HBO) addresses the revenge porn issue during a particularly poignant episode of its second season.

This travesty is even more cut-and-dried than that. This random stranger never had consent to view the photos in the first place (thus he had to hack phones and iCloud accounts to get at them), and he certainly never had consent to distribute them worldwide. If private financial information had been hacked and distributed, there would be no question as to the criminality of the action. The fact that it's private photos somehow makes the criminality uncertain. I can't even begin to understand that.

Again, it's all about consent, both the viewer and the person being viewed. If the viewer doesn't consent (a man exposing himself to pedestrians on the street), BOOP! onto the sex-offender registry with you. If the person being viewed doesn't consent (peeping toms and stalkers), BOOP! restraining order for you. But because revenge porn and celebrity photo leaks happen on the internet, and because there was consent at some point waaaay back in the process, nobody knows what to do.

Moving on.

Female bodies, sexuality, and expression as public property.

The examples and consequences of this issue are too numerous and widespread to mention them all. Restricting access to both birth control and abortions (at the same time) as an attempt to regulate and control female bodies and sexuality. Cat-calling and street harassment as an indication that a woman and her body are public property and open for comment. The 'third date rule' and similar ideas that entitle men to sex. Annnnnd the idea that hacking and releasing private photos of famous women was in any way ok. These women are famous, therefore I am entitled to see her tits. If the photos were intended to be the public property this maladjusted cretin assumed them to be, he wouldn't have needed hack them. And also, the men falling over themselves to find the photos once they were released. The photos exist, therefore I am entitled to see them.

The moral of this rant is, first, to cut it the hell out with the slut-shaming and the victim-blaming (I think I said that already). Second, in this new digital age where we have an infinite amount of information at our fingertips, most of us have at least some form of online presence and interaction with others, and everyone has a camera in their pocket, we need a new standard of law, morality, and decency. Or we need to follow the current standard along its logical extension into the digital realm. And third, a lot of these problems will fix themselves when we get over the shame and taboos about sex that we inherited as a society from our unfortunate Puritan founders. Taboos and shame wield terrible power in adults, and the only way to really get rid of them is to not teach them to our children. We need to give our children and young adults a proper sexual education that emphasizes safety and responsibility, consent and respect, pleasure and intimacy. Only then will the dregs of society be unable to hide behind the taboos to avoid justice and use the shame as a weapon of mass destruction.

Wednesday, August 20, 2014

Chickadees are T-rex's tiny and rather disappointing great (x100000000000) grandkids

From the Scientific American article.
Birds are really just really tiny dinosaurs... but best not to mention the 'tiny' part, they're pretty touchy about it.

But seriously... pretty much from the beginning of the theropod lineage (even before T-rex and velociraptors), they've been gradually getting smaller (some of them small enough to survive the K-T impact), until we had a chickadee in place of a man-eating colossus. They kept the feathers, discovering they were good for gliding and (eventually) powered flight, and lost the teeth (something had to give).

Here's the Scientific American blog's recap of the paper (pointed out by today's 10,000 Birds post), for those like me who don't have a subscription and aren't at a university any more.

(cross-posted)

Monday, August 18, 2014

Testing 1, 2, 3...

After realizing that my original Bander-and-Barista blog had gotten a bit off-topic in the couple of years since I left the field biology scene, I created this one to take its place for more regular-life posts, in addition to the cool science. It was supposed to be a bird banding and sciencey blog full of juicy tidbits and photos. But since the sad day I realized I couldn't afford to only get paid a living wage 6 months of the year, the blog had mostly just been regular daily-life stuff, with the occasional weekend birding outing or monthly trip to the semi-local banding station. I'm also no longer a barista. So. That blog (Bander and Barista) will now be confined to bird-ish things, even if it's just new installments on the banding memoir I'm attempting to write. That, in particular, is exactly what I started that blog for... science and ornithology and field biology and the adventures associated with them. The fact that the events in the memoir happened 6 years ago is the reason it's a memoir and not a blog post. There are even some old LiveJournal posts from that period, and those will also be part of the memoir. Occasional weekend birding outings and monthly trips to the semi-local banding station will still be featured here as well. Especially once we get to autumn and I can stand to be outdoors again. For the moment, the non-relevant posts are still there, but over time (since there are a lot of them) I'll be moving those to this blog, dedicated mostly to the regular life stuff. There will be some cross-over on this blog of stuff posted there, since bird stuff is also life stuff. Because of the cross-over, I'd advise that folks follow one or the other, but not both, if you don't want to deal with duplicate posts on occasion.

Edit: WOW. This is gonna be more effort than I thought. Of the mind-numbing copy/paste variety.

I'm also thinking it might have been easier to do this the other way around and change the name and URL of the original blog. Goddamn it.

Posts from the old blog that will eventually get copied here: