The Futile Cycle

From now until around May, I’ll be on the hunt for a Ph.D. advisor. Amusingly, I came across this Nature article on what makes good mentors at the same time that PhD comics had this strip:

I’ve been filling out a bare-bones hourly log of what I’ve been doing all day, so that I can look back at the end of the day and see what I have and have not done. I got the idea from Getting What You Came For, which is an interesting book (a review of it sometime later).

It’s going to be an interesting experiment. So far, it has been making me focus on what I’m accomplishing (and also on what I’m very much not) and what I spend my time on all day. Not only that, I have a log at the end in case I forget a couple days later whether I accomplished anything this past week. It feels like a good way to lend some structure to an otherwise very structure-less summer, where I don’t have work days, or really any work other than what I want to do. On the other hand, it does bring too much highlight upon hours that I don’t spend doing something “productive.” Is it bad to enjoy part of my day reading blogs? I don’t think so, and yet the log makes me feel as though I need to eradicate anything that isn’t work. So, perhaps the log is a bit of a double-edged sword.

I will continue for the next few weeks or so, and see if I feel like it’s helping my productivity, or whether it is just an unnecessary distraction and a source of unneeded stress.

I can only imagine how many Monty Python references are made when referring to this paper: Flight Speeds among Bird Species: Allometric and Phylogenetic Effects.

One of the things that is taking a while to get used to, moving to a new school, is the new (lower) level of online access to journals. My undergraduate university had pretty wide access to almost any biomedical or physical journal that I wanted access to. It might be because it had a medical school attached, or something. I was pretty spoiled.

My new university, though, doesn’t have a medical school, and (maybe as a consequence) it doesn’t have as much access to online journals. Now, I wouldn’t complain if some of the journals that I don’t have access to were really obscure, or if they were medical journals oriented purely towards clinical practice.

But the Nature subjournals?? I mean, they’re not that big, certainly not as big as their parent, but they have some very non-obscure things going on in there, and most are definitely not clinical journals. Not only that, but genetics is something that the new university is trying to push, at least in the past few years, and yet no Nature Genetics? No Nature Chemical Biology? Not even Nature Cell Biology?

Weird. Have I been spoiled too much by my previous university, or is it too unreasonable to ask for a few of the major second or third tier journals in their electronic form?

EDIT: Wow, I feel like a total goof. False alarm. For some reason, it worked this afternoon, though it wasn’t working no matter what I tried yesterday. I do have access to the Nature subjournals. Very strange, since other journals were working yesterday; it was only the Nature subjournals that weren’t…

My physics teacher tried to get this to work, but he never could. But Jay Leno has it down pat! Check out sulfur hexafluoride, a cool, pretty inert gas.

Madrid was an amazing experience, and there are some things I’d like to note. Firstly, try to visit a little earlier than July; it’s damn hot (it hovered between 90 and 110 during the day). Secondly, wear good shoes, as always on a tourist-y trip in Europe. Third, travel guides are good for metropolitan areas, but get out of date rather quickly for side trips (e.g. Toledo, El Escorial). Check ahead for closings, restorations, and rennovations of key things (e.g. the alcazar in Toledo). Lastly, plan to stop often for food and a drink break. It helps a lot.The GreatThe Crystal Palace is a definite thing to see, in the Parque del Buen Retiro. The lake near there is also very nice to sit by and laze an afternoon away on.Aloque (Torrecilla del Leal 20, M. Antón Martin) is an excellent, excellent wine and port bar, with very good raciones to accompany the wine; I recommend the carpaccio. Ask the bartend for suggestions if need be. His taste is very good.In fact, Lavapies is just a great area for dining and drinking. Good, friendly, cheap. Not as touristy as the areas near Sol and Gran Via, so spanish-speaking is a must, but they’re very patient and kind, with good suggestions. La Buga del Lobo was good.The Post Office on the Plaza de la Cibeles is amazing, like a giant castle.The Thyssen is very well organized and curated. They have a wonderful collection of art spanning many centuries of European work. Completely awesome.The Prado is awesome, with a huge collection of wonderful Ribera paintings, as well as a lot of Velasquez, Goya, and El Greco (of course). Very good museum, though organized a little difficultly.Las Tablas (Plaza de España 9, M. Plaza de España) is a great bar to watch flamenco dancing, a show that goes an hour and a half or so. We had a table right up at the stage, and the whole room was having a great time. The owners got up and danced afterwards, which was absolutely amazing. Food was a bit pricey. Get there early. The Plaza is also pleasent to walk through.Restaurante Sobrino de Botin was pricey, but worth it. A tourist trap, to be sure, but the food is still very good, and how can you resist the so-called “oldest restaurant in the world”? The roast suckling pig is like eating a slab of crisp bacon. I’m quite serious. The squid cooked in its own ink is also very good.The Real Academia de Bellas Artes de San Fernando is surprisingly good (we got in free, too). Among its twisting walls are some very nice Spanish works, and we discovered a few new artists that we hadn’t known about before.El Escorial was mindblowing. What a monastary. What a palace. What a library. It was kind of awe-inspiring to stand in the mauseleum with the coffins of Philip II and Charles V. Everything was wrought gold, jasper, and beautiful marble. Seriously, a burial befitting of one named Imperator et Rex – Emperor and King. Didn’t know we had to make a reservation beforehand to see the Bourbon apartments inside.The Palacio Real was also quite an experience. So this is how the king lives, huh? Much more extravagent than Buckingham, apparently (I’ve not been to England, but JZG has). Some rooms have embroidery instead of wallpaper. Just…wow. The view from the adjacent cathedral’s top is quite beautiful, too, thought the cathedral itself was underwhelming. The crypt below is kinda pretty.Toledo was very, very hot (43 C, 110 F), so that was a bummer, but the city was beautiful, like stepping back into the olden days, except without all the crap on the streets. Beautiful, monumental cathedral. The Casa Museo de El Greco was under rennovation, but the painting of the Burial of Count Orgaz was very beautiful, though crowded. The actual church (Iglesia de Santo Tomé) is quite a nice experience as well. Watch out for shoddily-made damascene; “hand-made” is often an outright lie.La Trucha (Calle de Núñez de Arce 6) was pricey, but so good. Definitely order the fish tasting tapas platter.Palazzo (Gran Via 32) has great ice cream.Basque food is heavenly, but I can only handle it in small quantities. Oxtail pan-fried and stuffed with foie gras was cold, hot, salty, oily, fatty, crisp, creamy, and every so delicious, but afterwards I distinctly felt a few of my arteries gasp.The OkThe Reina Sofia was ok. “Guernica” was obviously the highlight, but modern art doesn’t really do it for me. They don’t have many of the artists that I like, though they did have some excellent pieces from the Italian Futurists and Suprematists (who are not to be confused with “supremacists”). I find Joan Miró to be absolutely boring, hence eliminating maybe 1/3 of the collection from my consideration.Cerveceria 100 Montaditos was underwhelming, but the food was ok.The Convento de Las Descalzas was pretty interesting, but tiring (no places to sit for the entire tour). Rest before going. There’s also a long wait to get in.Casa Labra was too crowded, food wasn’t worth it.Shopping in Madrid is quite expensive, even places like Zara. Go to the outlets if you can.Plaza de la Villa was underwhelming at best.The view along the edge of Calle de Bailén was pretty nice, but not the fantastical view I was led to believe it was. Too much development had crowded it a bit.Chocolateria de San Gines is good, but the chocolate is so thick that it is pretty undrinkable, except to have with churros.Frommers has one or two good suggestions, but Lonely Planet is overall a more useful travel guide, I think. To Frommers, “Inexpensive” is still quite above my range of expense (i.e. a meal is around $25-30 per person), while for Lonely Planet, it’s a much more reasonable range of < $15 or so, it seems like. Still, it is useful to have at least two to cross-reference and check against each other.

By tips, I mean pipette tips. Alex Palazzo has an amazing data set on the order of pipette tip usage in his lab.

It’s a bit weird to think of prokaryotes as having cytoskeletons, since the most common dogma for undergraduate teaching tends to be that in bacteria, things just diffuse. Bacteria are small enough, the professor says, that they don’t need active transport systems that rely on the long polymers of the cytoskeleton. After all, an E. coli bacterium is only 1 micrometer long, and with the diffusion constant of an aqueous protein being around 0.1 μm² / ms, the time for proteins to diffuse from one side of the E. coli to the other is only a couple milliseconds. Really, (so the theory goes) is it surprising that bacteria don’t have a cytoskeleton? (The theory has been extended to analysis of purely physical methods of bacterial segregation, due to entropic considerations. Suckjoon Jun and Bela Mulder have a nice article in PNAS on this. An older paper describes a model of the bacterial nucleoid as a phase of supercoiled DNA.)

But in the last ten years or so, bacteria have been found to have many proteins that are very similar to eukaryotic cytoskeletal proteins, as well as a few that don’t have eukaryotic homologs at all. Mindblowing. I’ve been reading this review paper by Zemer Gitai to catch up. So, really, half the stuff they teach about bacteria to high schoolers and college students is wrong.

Though in retrospect, it’s not all that surprising that bacteria have cytoskeletons. How else would bacteria divide? Something has to squeeze the wall closed in between the two daughter cells, and it’s probably going to be some sort of cytoskeletal protein. It turns out that a tubulin homolog, FtsZ, forms a ring at the division site. In many mammalian and plant cells, we know that actin forms a ring and squeezes shut to cut cell apart (imagine a garroting wire forming a loop, and you have the right, though gruesome, idea). We don’t know exactly what FtsZ does, but it may have a similar role in bacteria. And bacteria also have lots of interesting shapes, which have to be maintained somehow.

One weird thing is how FtsZ is controlled by bacteria. Different bacterial species seem to use really different ways to control where FtsZ assembles. C. crescentus seems to use the most obvious solution, which is to have a protein that stops FtsZ assembly — MipZ — gather at the ends of the bacterium, so that the split away from the ends, right in the middle. B. subtilis uses a similar mechanism, with a different protein, MinC.

E. Coli, though, uses a really weird system, which is to have MinC form at one end, recruit another protein (MinE) which disassembles it, and then form again at the other end. So, essentially you have MinC turning on and off on either end of the bacterium, which forces FtsZ to form right in the middle. But why go through all that trouble? The oscillator also doesn’t seem particularly stable, the way it’s conceived right now, so there’s definitely something more to this oscillatory behavior than what’s known right now.

Anyway, I’m really curious as to the future discoveries on the bacterial cytoskeleton. I’m not only interested in the biochemistry, but also on the evolutionary side of things. Did eukaryotic cytoskeletal proteins evolve from this prokaryotic stuff? Harold Erickson seems to think so, even with the large sequence differences between the prokaryotic and eukaryotic versions. This could lead to interesting insights on eukaryotic cell shape, by simply studying bacterial shape.

And bacterial cytoskeletal proteins might just be different enough to make interesting broad spectrum antibiotics in the future.

The summer has made my posting schedule more lethargic, because I now have time to dedicate long, solid hours to teaching myself proper statistics, bioinformatics, reading review articles, and choosing professors to rotate with. In addition, planning for the event below has been keeping me very busy.

Anyway, even this trickle of content will be coming to a halt for about two weeks, as I will be off on vacation to the very middle of the Iberian peninsula: Madrid!

On the BBC, Israeli scientists try to circumvent chemotherapeutic sterility for girls with cancer. Essentially, the problem is that little girls with cancer can generally be cured with chemotherapy, but the aggressive regimes can sometimes leave the girls sterile. Thus, what the scientists did was isolate (surgically) unmatured oocytes and chemically induce them to mature, turning into eggs, which can be frozen to be used for in vitro fertilization (IVF) later in the girl’s life. An interesting idea, essentially “time-shifting” the eggs.

Anyway, they have a strange quote from an activist, Josephine Quintavalle, who demonstrates that she doesn’t know biology very well:

Josephine Quintavalle, of Comment on Reproductive Ethics expressed concern that if the eggs were donated to a woman of childbearing age, a resulting child could have a biological mother who was only a few years older. She said: “Are we going to end up with a child who has a mother who is just six years older? What happens if the child dies? Could the eggs be donated to someone else?

In case Ms. Quintavalle doesn’t realize, the current model of egg maturation in humans is that eggs essentially remain dormant, and usually only one matures at a time during each menstrual cycle (if more than one matures, it can lead to fraternal twins, triplets, etc.). Which means that a woman’s eggs in her ovaries haven’t aged very much compared to the woman herself, anyway.

To put it another way, let’s say someone donates eggs, and they sit for 100 years until someone else uses them for IVF. Assuming the science can actually do that, is it wrong that the “biological mother” (i.e. the egg donor) might be some 120 years older than the child? It’s not really any different (from an ethical point of view) from having the egg donor be a 5-year-old. Eggs are eggs, as long as they’ve matured properly. Now, there are plenty of objections one can make on the biological viability of the eggs, or the ethics of creating life by a procedure that may or may not lead to unexpected health consequences. This objection seems pretty groundless.

Strange that an activist on “reproductive ethics” would demonstrate so little knowledge of human biology. Really, what Ms. Quintavalle is exhibiting is nothing more than being squeemish:

I feel uncomfortable about this development.

That’s really the only thing she’s correct about.