Richard Dawkins The Root of all Evil Part I

yup

The blog is moving

Yes, I had mentioned this to some of you, and now it's finally come to fuition - my blog is moving to Science blogs. The new address is:

http://scienceblogs.com/transcript/

Enjoy!

Eye Candy

Well writing a paper makes you feel beaten-up. But now that it's done I feel better. (Hope the reviewers like it).

PS Guess what's I've captured in this image.

The Picture of a Happy Scientist!

So my blog's been suffering from neglect. (I'm writing up a paper.)

Hopefully it'll get in some journal, then I'll be a happy scientist!

Speaking of happy scientist, check this photo out (to the right).

And why is he happy? He not only just published a paper but is on front page of Harvard's website. Check out the Harvard article, and the original article in Nature Chemical Biology. What a golden moment!

{Update}

I've been asked to save the actual webpage cover for future reference ... I've done one better and pasted it on the blog:

Notice that Brian's paper is a bigger news story than Larry Summers' departure. Ah success!

{Update 2/28/06}

Basic summary: Brian found that Gold, platinum, and some other heavy metals can bind and inactivate MHC II and thus be used to treat autoimmune disorders.

Brian told me that when he discusses his results with many western doctors they are not that interested, while doctors from the developing world are enthralled. Not only is this treatment cheap, but it turns out that many local remedies for arthritis and other autoimmune diseases involve heavy metal administration.

Ref: Stephen L De Wall et al., Noble metals strip peptides from class II MHC proteins. Nature Chemical Biology, Published online: 26 February 2006

Mimivirus

While reading, Keat's Telescope, I read an interesting entry on Mimivirus.

I've been reading a bit on this weird creature. Last year its genome was sequenced (see the Science article). It is 1.2Mbp (longer than some eubacteria) and has over 10,000 genes, some of which are house keeping genes such as tRNAs and amino-acyl transfer RNA synthetases (proteins that load up the tRNAs with amino acids). Infact it was originally thought to be a bacteria, you can see it by light microscopy ... then someone looked at it in an EM (electron microscope) and saw it's true nature. In comparing it's house keeping genes to homologues in bacteria and eukaryotes, it's thought that Mimvirus is so ancient that it may represent a fourth branch in the tree of life (along with eubacteria, archaebacteria and eukaryotes).

To read more, check out the March edition of Discover Magazine.

Refs:
Bernard La Scola et al., A Giant Virus in Amoebae. Science (2003) 299:2033
Raoult et al., The 1.2-Mb Genome Sequence of Mimivirus. Science (2004) 306:1344 - 1350

Some General Comments about Larry Summers

So the news is all over the papers. Of all the articles I've read this morning, the most appropriate is Alan Dershowitz's OpEd in the Boston Globe.

I didn't agree with everything our President said, but in the end his goals were to provoke debate. Yes there were other problems ... his relationship with Cornell West, his confrontational style ... but in the end his comments about women in Science did him in.

But just as I hated the review by Leon Wieseltier (see here) it pains me to read the comments of all those who wanted Larry to step down due to the comments on sex. It is worth it to go and read what Larry actually said. He wanted to open debate and stimulate research concerning this topic. I do believe that Academia has a duty to investigate why the differences between men and women in many endeavors, but my guess is that both those of the right and left of the political spectrum would be surprised by the potential findings.

We may not agree with what Larry said, but the proper answer is to study the matter further not stifle debate (and use personal attacks to change the subject). My biggest guess is that to get to the top of Academia, takes a lot of (ridiculous) sacrifice and here is why more women than men opt out. As postdocs we get next to nothing to help support families etc. it's hard to justify staying in Academia ... and I don't have to worry about pregnancy. And in my opinion, something has to be done about it. The problem is not Larry, and it's not men vs women, IT'S THE SYSTEM.

For the record ... I've copied an entry from my old blog about the speach in question.

---------------------------------------

Friday, 18 February 2005

Larry Releases Transcript

Well here is the transcript!

This was part of a speech on gender ratio imbalance in Math and Engineering. What is the ratio of men to women in other fields? High up, it's not much better.

Well he starts off with a strange comment:

It is after all not the case that the role of women in science is the only example of a group that is significantly underrepresented in an important activity and whose underrepresentation contributes to a shortage of role models for others who are considering being in that group. To take a set of diverse examples, the data will, I am confident, reveal that Catholics are substantially underrepresented in investment banking, which is an enormously high-paying profession in our society; that white men are very substantially underrepresented in the National Basketball Association; and that Jews are very substantially underrepresented in farming and in agriculture. These are all phenomena in which one observes underrepresentation, and I think it's important to try to think systematically and clinically about the reasons for underrepresentation.

What a bizarre mix of things to say!

And the relatively few women who are in the highest ranking places are disproportionately either unmarried or without children, with the emphasis differing depending on just who you talk to. I agree! A career in the Sciences (or most professions) is not compatible with raising a family. But I think that this is also true for fathers.

Larry may have a point in that usually women bare the brunt of the child rearing. However I believe that it's easier for husbands to dump this responsibility on their wives and this maybe facilitated by the type of society we live in.

... and the work that Claudia Goldin and Larry Katz are doing will, I'm sure, over time, contribute greatly to our understanding of these issues and for all I know may prove my conjectures completely wrong.

I'll have to look in to these studies ... Now on to IQ ...

I looked at the Xie and Shauman paper-looked at the book, rather-looked at the evidence on the sex ratios in the top 5% of twelfth graders. If you look at those-they're all over the map, depends on which test, whether it's math, or science, and so forth-but 50% women, one woman for every two men, would be a high-end estimate from their estimates. From that, you can back out a difference in the implied standard deviations that works out to be about 20%. And from that, you can work out the difference out several standard deviations. If you do that calculation-and I have no reason to think that it couldn't be refined in a hundred ways-you get five to one, at the high end. Now, it's pointed out by one of the papers at this conference that these tests are not a very good measure and are not highly predictive with respect to people's ability to do that. And that's absolutely right. But I don't think that resolves the issue at all. Because if my reading of the data is right-it's something people can argue about-that there are some systematic differences in variability in different populations, then whatever the set of attributes are that are precisely defined to correlate with being an aeronautical engineer at MIT or being a chemist at Berkeley, those are probably different in their standard deviations as well.

Well it's hard to say whether these 5th graders are already "socialized". Also why are there more women (than men) enrolling in college. Does US society affect this? In Canada medical school is dominated by WOMEN!

So my best guess, to provoke you, of what's behind all of this is that the largest phenomenon, by far, is the general clash between people's legitimate family desires and employers' current desire for high power and high intensity, that in the special case of science and engineering, there are issues of intrinsic aptitude, and particularly of the variability of aptitude, and that those considerations are reinforced by what are in fact lesser factors involving socialization and continuing discrimination.

Well that's still up for debate. My own opinion is that the clash between family and career, and socialization (the two of which ARE related) are probably the main cause. The lack of support from institutions (such as Harvard which due to its prestige can get away with throwing scraps to it's professors) is also a big problem. Here at the Medical campus the "new research building" was recently completed. I was told that when asked what facilities should be included, most faculty and staff replied "daycare facilities". What did they build? A gym!

I would like nothing better than to be proved wrong, because I would like nothing better than for these problems to be addressable simply by everybody understanding what they are, and working very hard to address them.

Cute Larry... Well if anything this episode will be good in the longterm. These are issues that need to be discussed.

The only other question is: Will Larry survive?

Larry's Gone

Well rumors were flying around all morning. Then we heard something on the radio. Now sitting down at my laptop this afternoon to check my email ... this:

From: Lawrence Summers [official@harvard.edu]
Sent: Tue 2/21/2006 1:05 PM
Subject: Message from President Summers
Attachments:

Dear Members of the Harvard Community,

I write to let you know that, after considerable reflection, I have
notified the Harvard Corporation that I will resign as President of the
University as of June 30, 2006. I will always be grateful for the
opportunity to have served Harvard in this role, and I will treasure the
continuing friendship and support of so many exceptional colleagues and students
at Harvard.

Below are links to my letter to the community, as well as a letter from the
members of the Corporation and a related news release.

Sincerely,
Larry Summers

http://www.news.harvard.edu/gazette/daily/2006/02/21-summers.html
http://www.president.harvard.edu/speeches/2006/0221_summers.html
http://www.news.harvard.edu/gazette/daily/2006/02/21-board.pdf

I guess that's the end of the Summers Saga.

Why rant when the blogosphere can rant for you

This Sunday in the NY Times Book review section, I read a horrible review of Daniel Dennett's book Breaking the Spell: Religion as a Natural Phenomenon. I wanted to write up a blog entry or a letter to the editor, but I had too much stuff to do.

I haven't read it, but I've read several interviews (one in the NY Times Saturday Magazine) about the book. Dennett's has two proposals ... first that academia should study the reason why humans have religion - as in the biologically/evolutionarily based reason why we've developed religion, and second, does religion confer any benefits to individuals or to society.

In other words, did the belief (or predisposition) in religion offer some benefit to our ancestors? And today, is religion making you happier, healthy ... ?

Instead of a critique, the review by Leon Wieseltier offers an incoherent analysis of the whole endeavor of academic research. In addition, the review is laced with personal attacks, as in

In his own opinion, Dennett is a hero.
...
Dennett is the sort of rationalist who gives reason a bad name; and in a new era of American obscurantism, this is not helpful.
Dennett flatters himself that he is Hume's heir.
...
In the end, his repudiation of religion is a repudiation of philosophy, which is also an affair of belief in belief. What this shallow and self-congratulatory book establishes most conclusively is that there are many spells that need to be broken.

And there's more ... Dennett has "naturalist superstitions" and spreads "Scientism". Wieseltier attacks Dennett's reasoning by reasoning that reason can't be used to study religion. What the bloody hell??? In other words, please don't ask rational questions.

Do I need to write more? Yesterday, I was amazed by all the fuss generated in various blogs on the subject of the book. So instead of repeating what they said, go and read them.

Brian Leiter
Silly Humans
Pharyngula
Stumblings in the dark
The Little Green Blog
Shotgunfreude
The Secular Outpost
Science and Politics

Scientists Taking Holidays?

Yes it's President's Day, but does that stop the lab from filling up?

If you are concerned that Holidays may slow down the pace of Science, fear not, Scientists have lost the ability to take time off! (or perhaps to identify major holidays/weekends)

This fact was seared into my brain last night. I had to stop by the lab to poly-adenylate some RNA I needed for an experiment, and who do I see in the lab at 10:30PM on a Sunday night of a three day holiday? Not a desperate postdoc, or some struggling grad student, (well that's not true, I found one of those in the computer room), but a lab technician. When I asked him, "what's up?" his reply was, "concentrating protein and reading my novel".

Amazing.

A Slice of Life Scarves

As a microscopist you are often are stunned by the beauty of what's on your microscope slide. I remember as a grad student showing this technician (a former doctor from China) a slide where cells were stained by immunofluorescence against microtubules. After peering into the microscope he turned to me and said, "there must be a God". Yes quite beautiful stuff.

So it came as no surprise when a good friend of mine sent me a link to A Slice of Life Scarves. This company uses motifs from the life sciences as patterns for their scarves and ties. Besides Golgi scarves (left) and centriole ties, they even have sarcomere ties (for those power meetings!)

Bimolecular Fluorescence Complementation

Just read an article in the last issue of JCB, where the authors used a nifty new technique to investigate when and where certain RNA binding factors associate together.

What's neat, is that this technique, bimolecular fluorescence complementation (or BiFC) works by fusing each half of a fluorescent protein (in this case yellow-fluorescent protein; YFP) to two proteins of interest (in this paper the RNA export factor TAP/NXF1 and the RNA binding factor Y14). To regenerate the intact YFP molecule the two proteins in question must come together. Since the fluorescence can be monitored without fixatives you can mow monitor this potential interaction in living cells.

In the past researchers used a related technique called FRET, or fluorescence energy transfer, to demonstrate the interaction of proteins in live cells. It works by fusing one type of fluorophore (say fluorophore "A") to protein #1 and a second type of fluorophore (say fluorophore "B") to protein #2.

If the two proteins came close enough, when excited, fluorophore A can donate (or transfer) it's energy to fluorophore B.

Stimulate A, measure B.

The problem is that when you stimulate fluorophore A, a fraction of it's emitted light overlaps with the fluorophore B's emission spectrum. In addition when you excite fluorophore A, some of fluorophore B will get excited directly (i.e. not by energy transfer) and emits some light. These sources of non-FRET fluorescence contribute to background or noise, and limits your detection. As any good microscopist knows detection = signal/noise. So the only way to determine the amount of fluorescence caused by FRET, is to perform very precise measurement to get the values for the noise (background fluorescence) and total fluorescence (FRET + background) of the experiment. Often FRET changes the fluorescence by as little as 10% of the total fluorescence ... not a very high signal to noise ratio!

With BiFC, fluorescence will only occur once the two YFP halves come together ... thus reducing the backgroud and increasing the signal to noise ratio. The authors provide data that the two YFP halves don't interact on their own, so BiFC can only result if TAP and Y14 get close to each other. One nice result from these experiments was that although the TAP protein is found primarily at the nuclear rim, the BiFC fluorescence (and hence TAP-Y14 association) was seen in another part of the nucleus, in speckles. When the authors swapped which YFP half was attached to TAP and Y14, BiFC wasn't observed indicating that for BIFC to occur, the two halves of YFP have to be not only close to each other but also correctly aligned. In addition the authors only observed fluorescence when the RNA binding motifs of both TAP and Y14 werefunctional, suggesting that the two proteins associate together when bound to a transcript (i.e. mRNA).

So in summary here's another tool to monitor protein interactions in cells. We'll have to see whether this technique can be used for other protein combinations. OK that's enough flashy science for today ...

{Update 2/18/06}

Here is image 1 from the paper described above. They show BiFC fluorescence, staining against the C-terminal half of YFP (YC), DNA (DAPI) and a color merge. This as a good example of using black and white images to present data. If you wonder why the image looks strange, the authors have inverted the B&W picture (i.e. black=fluorescence, white=no fluorescence). This type of data presentation can often help to display very faint patterns. If you look in "B" Y14 is found in speckles while TAP/NXF is localized to the nuclear rim.

Ref: Ute Schmidt, Karsten Richter, Axel Bernhard Berger, and Peter Lichter, In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains JCB (06) 172:373-381

Postgenomic: The Biomedical Science Blog Clearinghouse

Just read a post from Evolgen, about this new biomedical blog aggregator started by the Flags and Lollipops blog. It's called Postgenomic.

Once in the site you'll find links to blogs entries that review papers, science meetings and hot discussion topics. Also this site features lots of stats, like "the wordiest science blogs". Incidentally according to the stats on that page I'm pretty wordy 373 words/post or #15 out of 66 listed blogs ... I'm not sure whether this is good or bad.

(BTW This post will definitely lower my word count!)

More Media

No, not he type used to feed cells (or gradstudents), but webcasts, podcasts and films.

First, Robert Write has an interview with Edward O. Wilson at his site meaning of life tv (which incidentally has lots of great interviews). I like Wilson's take on the difference between Science and all other human organizations ... IDers take note. [From the Gene Expression blog.]

Next Science magazine finally got it's act together and are now producing a weekly podcast (a little more in the style of NPR than Nature's podcast). Interestingly they us a piano riff (between segments) that's yanked off one of my favorite albums, Medeski Martin Wood's Notes from the Underground. [For MMW fans, this is their first and only TRUE jazz album before they did hokey techno-infused pseudojazz - to get a feel of this album listen to this clip.]

Finally I saw a great movie, Cache ... it's comprehendable if you do see it keep in mind West/Middle East relations and the Iraq war. To read more (including a spoiler) see my analysis at the Cache website.

Further Differentiation within the ER

OK this week I've been obsessed with the endoplasmic reticulum (ER). This organelle is comprised of a continuous network of membranous tubes (and sheets) that extends to the cell periphery. In addition ER sheets also envelopes the nucleus - forming a bilayered nuclear envelope with an outer nuclear membrane and inner nuclear membrane.

Here's a pic of the ER from a previous post:



The extended part of the ER though is mostly tubular, as I displayed in an earlier post on Immunofluorescence images:



So the question becomes ... how do you form tubular organelles?

Well Gia Voeltz, from our lab just published a paper in Cell on how a class of proteins (Reticulons and DP1-related proteins) are responsible for this architecture. Reminiscent of an earlier post where I described how Nesprins are confined to the outer nuclear membrane (and thus help to differentiate that portion of the ER), reticulons and DP1 define another part of the ER, the reticular or tubular part. So reticulons are excluded from the nuclear membrane. But there's more, Gia used an assay to form tubules in vitro (i.e. in a testube) from ER vesicles derived from frog eggs. She could inhibit the tube formation by modifying reticulons or by adding antibodies against reticulons. In addition the way reticulons are inserted into the membrane is not typical of most membrane proteins, and this strange "topology" may help them to curve membranes and thus help to form tubes.

Here are a black & white images with a color overlay (from Gia's paper), that demonstrate the unique distribution that reticulons adopt. Notice how a general ER marker (Sec61-beta) is in the tubular portion and in the nuclear envelope, but that reticulon4a (also called NogoA) is only found in the tubular ER. Note how the black and white image of Rtn4a (but not the color overlay!) clearly demonstrates how reticulons are excluded from the nuclear envelope.

To read more check out the paper.

Ref: Gia K. Voeltz, William A. Prinz, Yoko Shibata, Julia M. Rist and Tom A. Rapoport, A Class of Membrane Proteins Shaping the Tubular Endoplasmic Reticulum Cell (2006) 124:573-586

Interview with Bil

It's Friday night, I'm in the lab writing my paper when who pops up in an IM chat screen? Bil the man. He's starting up a new lab in California. We chatted a bit ...

Mad Scientist: man I should do a blog "interview" with you

Bil the Man: Right.

MS: (just another excuse not to work on the paper) ok here goes

BtM: Dude, I have sht to do.

MS: so do I

BtM: Yeah, well, if you don't need quick answers. I'm writing my first e-mail to an undergrad interviewing next week.

MS: What's the best thing about becoming a PI?

BtM: The best thing is that I get to make all the decisions. The worst thing is that I have to make all the decisions.

MS: Anything you didn't anticipate?

BtM: As a PI there is a lot of administration, a lot of politics, and lots of decisions. It is really easy to stay busy. I'm only taking baby steps and it is already very complicated. The money also goes really fast.

MS: Really, out of money ... what are the big ticket items?

BtM: Centrifuges burn the money fast. I regret buying one of them already but hopefully it won't be a big mistake. Also, they come with rotors at over 5K each. That package cost me nearly 200K. Incidentals add up fast too. I'm looking at a 20K order from Fisher/VWR.

MS: That's why Tom is constantly obsessed with rotors ... so what's the status on the lab? When will you be pippetting away in there?

BtM: We'll be starting in about 2 weeks I hope. All the big stuff should be here by then. That will be almost exactly 2 months from day 1. My Tech is aching to start pippetting. I hope he feels the same way in 2 months.

MS: Are you excited? Anxious?

BtM: I'm anxious. I really want to get started. I don't want to rely exclusively on others supplies so I'm waiting a bit. We'll be moving pretty fast once we get started. I think the two people I have so far are capable of a lot of output.

MS: I'm impressed that you don't feel (or appear to feel) overwhelmed. Do you ever think to yourself "man I'm responsible for all this money, people etc."?

BtM: Not really, I feel a lot or responsibility but I don't feel like that is complicated. I've made a few mistakes but those were learning mistakes. ie If you don't know for sure get advise. I have a lot of support from the other faculty. I feel overwhelmed that little of what I've been doing involves the details of the science. So far it has all been about setting up the lab and administration. I'm looking forward to talking science in a real way again. Hopefully my lab will give me that.

MS: Ok I should be going for dinner soon so one last question. If you were to guess, when is the first big paper coming out?

BtM: Oh man, I don't want to jinx anything. I'm hoping the next interesting paper will be SecY mutants....

MS: Thanks ... one of the best interviews I've had so far ... well thought answers, I guess that's why they hired you (well not really)...

BtM: Man, you have no idea how serious this job makes you. I'm looking forward to relaxing once we are focusing on research.

MS: That's why you're always talking about the beach ...

BtM: Have a great weekend. Give our best to your missus.

MS: Thanks you too, say hi to {wife - not sure if Bil wanted his wife's name on the net}

Immunofluorescence

OK here's a post geared mostly to cell biologists. My big pet peeve about reading the scientific literature is ... colored fluorescent images.

Why do people insist on pseudo-coloring their images? I know that you want pretty pictures and as every kid knows the more colorful the picture the more adoration one gets from approving parents ... but we're talking about data and instructing/convincing your fellow peers about new findings.

So why is color bad for data presentation?

• Your eye is better at detecting various shades of grey than shades of any hue. Or to rephrase, it's easier to detect details in a black & white image.
• Your eye can also simultaneously detect many more shades of grey than any hue. This is sometimes called dynamic range. If your protein is enriched in one area of the cell and sparse in another location, it's easier to convey the range of concentrations in black & white.
• Then there is the famous green/red overlays. I hate those! You can never tell whether an area is green (just protein 1) or yellow (protein 1 & 2).

So let me illustrate (literally!) what I mean:

Here is the same image (of a protein localized to the endoplasmic reticulum) in black white, and the 3 colors commonly used:




You're thinking, well it isn't so bad ... but in a journal article these images are usually scaled down ... lets do that.









Besides the blue pic, they're still not too shabby ... but go ahead and print these 4 images and all detail will be lost in the red and blue images. Greens tend to fair a bit better, but the black and white will be just fine and clear. Yes clarity is the aim of data presentation, not pretty pictures.

Blog pains

Just had a long conversation with a good friend from NY. We talked about science, careers, how the locals back at Columbia University are faring ... and of course about blogs.

It's funny, back in grad school, we had many conversations about reaching out to the public and spreading the gospel of science (and no I'm not implying that science is like a religion). In a way, I guess that's what this blog is about. Although I have the suspicion that most of the readers are scientists themselves (or even biologists).

This inkling that no non-scientists ever come to my blog is compounded by the fact that I've been banished from Google.

It use to be that you could type in "daily transcript blog" and my site was hit #2, now it's something like hit #700. I used to get lots of traffic from Google from people who would perform searches on "blog mRNA" or "central dogma of biology", but no longer. Now my traffic from Google has gone to zero (although Google's blog search lists my entries just fine). So plain unsuspecting folk can only get to my site by searches in Yahoo and MSN (something also happened to my Technorati entry), or via direct links.

I've read up on why Google may ban your site, and I'm quite sure that this is indeed what happened. In fact listed in the top 10 as a hit in Google for "daily transcript blog" is another site "Daily Transcript Q&A". This was a site I accidentally set up when blogger told me that the ribonucleicacids URL was not available (which it wasn't). So I had registered this site without knowing it. Well instead of deleting this second site, I decided to add some info to it (hence the "Q&A").

Actually the VERY first URL I entered was "ribonucleicacid.blogspot.com". Again blogger told me that this URL was taken, but again it in fact registered this site under my user name. For a while this URL just sat there. Then one day I posted an entry directing traffic from that URL to this site "ribonucleicacids.blogspot.com" (singular vs. plural) - why not. Well I'll tell you why not ... this was probably the cause of the Google (and Technorati) ban. Creating websites to boost your links.

Oh well, who needs Google anyway?

(and yes I know, they own blogger)

Science in Action

Portuguese (tissue) culture:

Looks like she's mouth pipetting, or drinking (we're not sure) some yummy tissue culture media. I hope that this newspaper clipping won't spark riots.

Article on Peer Review

I read an interesting article in The Scientist on how the NIH wants to evaluate the peer-review process for NIH grant applications.

Some facts about NIH grants:

• Average age a researcher gets his/her first R01 grant: 42 (as I've mentioned in a recent post).
• Time between grant submission and grant acceptance: average of 9 months.
• Percent of R01 grants that go to new investigators: 6%.

This article is a partial follow up of a commentary (also published in The Scientist) by David Kaplan of Case Western on the peer review process in general. If you've had bad experiences with the whole review process, you'll applaud Kaplan.

Eye Candy

It's Friday ... here's a cell stained against mRNA from an artificial gene.