Thursday Links

Lazy August links:

  1. Ray, the parking robot:

    [T]he system could work fine without any human oversight, but the airport is having an employee on hand in case travelers have questions about how to use the new option.

  2. OKCupid experiments on human being! But because they don’t publish in scientific journals and do it just for fun and profit, that’s totally OK (unlike the facebook study, which was unethical because they published).

Friday links

  1. A last link on the facebook saga makes the observation that if facebook just includes some randomness in all decisions of what to show on the stream (which they might do just to improve their service), then any study which leverages this is a randomized observational study. And observational studies have much reduced ethical thresholds.

  2. An excellent summary of what is known about SSRIs. I really liked both the conversion of effect size to weight loss numbers and the discussion of how, whilst people can agree on the data, it gets very hairy when you start to use words such as “moderate depression” or “severe depression” to describe different numeric results.

  3. Some people who make more money than I do, can activate your DNA. Obviously, they are skeptical of ENCODE claims. This guy’s biography is perfect:

    Toby Alexander, is a coach, speaker, seminar leader and author. He is a leading expert in a variety of fields including energy medicine, emotional mastery, peak mental strategies for optimal performance, 15th dimensional physics, futures and forex trading, SAP, remote viewing, and distant healing.

  4. Next week, I’ll be in Lisbon for LxMLS 2014. Contact me if you want to get in touch there.

New Paper: Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo

(This is a guest post by Ana Pena, who is  the first author of Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo, a paper I had a small hand in).

 

Pena_Paper_Figure3(Panels A & B from Figure 3 in the paper, showing effects of RNAi knockdown of H1)

The organization of DNA inside the eukaryotic nucleus relies on what we like to call the “beads-on-a-string” structure of chromatin, in which nucleosomes are the “beads” and DNA is the “string” around. While we already know a lot about the histones that make up the nucleosome, the functions of the “extra” histone, histone H1, only now start to be uncovered in vivo.

Histone H1 is a small protein that sits outside the nucleosome “beads” and binds to the DNA between them. In this work we explored the role of histone H1 in Trypanosoma brucei, a unicellular parasite responsible for Sleeping Sickness. Genome-wide RNA expression revealed an interesting fact in this parasite: histone H1 acts mainly as a repressor of a particular cohort of genes, which are transcribed by RNA polymerase I and are essential for its differentiation and survival inside the host. To understand if histone H1 represses transcription at these loci, we performed metabolic labeling of nascent RNAs with 4sU for the first time in this parasite, showing that histone H1 silencing effect is exerted at the transcriptional level.

Full paper citation

Pena AC, Pimentel MR, Manso H, Vaz-Drago R, Neves D, Aresta-Branco F, Ferreira FR, Guegan F, Coelho LP, Carmo-Fonseca M, Barbosa-Morais NL, Figueiredo LM. “Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo”. Mol Microbiol, 2014 Jun 19. doi: 10.1111/mmi.12677.

 

Dealing with a dry spell

In the last 12 months, I had 6 papers published [1] (two as first author, four as middle author). I currently have another 3 in review plus another two close to submission (two more submission before the end of the year are likely).

Awesome productivity, right? It wouldn’t be bad for a small lab to get a paper every two months and I’m just a guy with a laptop.

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Unfortunately, these numbers reflect not just the fact that I’m both extraordinarily productive and work long hours [2], but also the fact that for the previous two years I didn’t have anything come out.

During those days, all of my work got stuck in different stages of the pipeline without seeing the light of print. I did do other things, like move between countries (twice), I did have other things happen (like writing a PhD thesis and what not), but no papers published.

I did submit manuscripts. They got rejected after (sometimes long) reviews. Sometimes, they got rejected twice for good measure.

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This post will surely get some google hits from people who think it’s about how to deal with not having sex for a long time. It is not. But if it were, it wouldn’t be that much different.

When you keep submitting manuscripts and they keep getting rejected, you start to lose confidence, you lose your edge, you doubt yourself. This applies not only to the submission process per se (submitting the manuscript, where you start to procrastinate with more-or-less finished work) but to the everyday practice of science, you start to lose the scientific killer instinct. You succumb to analysis paralysis.

Fear is the mind killer.

Much of what I do (we do, as scientists) is try to swim in the ocean of analysis possibilities and false hypotheses to find a current which I can pursue to a pot of gold. It’s not a needle in a haystack. Needles may be difficult to find, but when you do find them, you are sure you have a needle. If you are (un)lucky, you just sit on the haystack and the needle will announce itself on your behind. Good scientific hypotheses are not like that. They hint at you, look very much like bad hypotheses, and are hard to distinguish from the morass.

I feel rather that I swim around trying to detect hints of a current. The currents are there, but so are waves and fish and other divers trying to confuse you. The trick is to feel the vague hints of a current and then systematically show that it is there. Most of the time, though, your hypothesis of a current turns out to just be a whale fart [3]. However, you need to have enough of a killer instinct to pursue these whale farts one after another until you find the right stream. When you lose confidence, you risk swimming around aimlessly, dismissing even true currents as whale farts.

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Eventually, though, the coin tosses of peer review started going my way [4].

In the meanwhile, this experience made reconceptualize a large part of the process. For example, I now no longer see submission as a goal, but as an intermediate milestone. At CMU, there is an annual event, called the Random Distance Run where the length of the race is decided randomly partway through the race.

The exact number of laps will be specified by the sum of two ENORMOUS FUZZY DICE rolls – one occurring just before the start of the race, and one just before the first runner finishes the number of laps specified by the first dice roll.

Getting a publication is the same, when you submit, you are at the point where a new die is cast. You may be near the end of the race or you may not.

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At one point, I commented with someone that all my stuff seemed to fail in review. They said something to the effect of it must be hard to keep failing and I just said when you’re in science, failing is the job.

Failing is the job.

Fail. Fail again. Fail better.

—Samuel Beckett

[1] Onetwothreefourfive, and six (post forthcoming).
[2] Even though both of these are true.
[3] I’m pretty sure that whales fart. Whales probably have an awesome microbiome.
[4] Yeah, yeah, peer review is not only random.

Saturday Links

1. Bioimage informatics conferences in Leuven and in Oporto

2. BBC Horizon 1977-1978 on the introduction of computers The only thing that is outdated about this documentary are the fashions. Mike Cooley, an union leader claims:

It may be necessary for individual nation-states to make clear decisions about what kind of development and society they want, and, if necessary, be prepared to protect themselves from the ruthless introduction of this kind of equipment [automation using computers] by the multinational corporations.

3. New face of biology? Outsource wetlab work, keep analysis in house? For many studies this makes way more sense than the often proposed opposite (do wetlab in house, outsource analysis to the cloud).

Two more links about the facebook study

From Wired,Everything You Need to Know About Facebook’s Controversial Emotion Experiment, making the argument that an IRB reviewing the study would likely have approved it:

The [hypothetical] IRB might plausibly have decided that since the subjects’ environments, like those of all Facebook users, are constantly being manipulated by Facebook, the study’s risks were no greater than what the subjects experience in daily life as regular Facebook users, and so the study posed no more than “minimal risk” to them.

Also, see here:

[C]ritics of the Facebook experiment should at least be aware that we are talking about a mode of research that existed long before Facebook, and that federal ethics advisors and regulators specifically decided that it should proceed.