Well, a whole room full of them, actually, but also the proud nerd and meeting crasher Christie Wilcox, who, I now learn, has a darned good set of pipes.

This session is all about pattern formation, focusing on those earliest, simplest decisions. How doe a mass of identical cells distinguish themselves inti regions with different patterns of gene expression. You might recall that this is the question that so baffles the creationist Paul Nelson. Nobody is going to give a moment’s consideration to his concerns, because they aren’t at all interesting.

10:30-12:00 Session 2: Pattern Formation (Chair: Vernadeth Alarcon [Univ. Hawaii])

10:30-11:00 Vernadeth Alarcon (Univ. Hawaii) “Cell polarity and differentiation in the early mouse embryo”

Studying the preimplantation mouse embryo, and the cell fate decision of committing to extra embryonic tissues vs embryo proper: trophectoderm(te) vs inner cell mass (icm). How does the embryo make TE? TE cells are polarized- they have apical and basal sides; does this play a role in differentiation? Found homologs to nematode partitioning defective genes (pard6b) that may be part of the mechanism. Knockdowns of pard6b leads to failure of blastocyst formation. It is essential for epithelialization of cells, which is a consequence of polarization. Knockdown also leads to reduction of trophoblast derivatives, while ICM derivatives are upregulated. 

Another gene involved in trophoblast differentiation is tead4. Tead4 knockdown also leads to failure of blastocyst formation.tead4 doesn’t seem to effect epithelialization, though — cells stilm make tight junctions independently of trophoblast differentiation, suggesting that these are separate pathways regulated by pard6b.

  11:00-11:30 Magdalena Zernicka-Goetz (Univ. of Cambridge, UK) “Mechanism behind formation of distinct cell lineages in the mouse embryo”

Let’s add more decisions: ICM vs TE, then Epi vs PE, then AP axis. Multiple competing models for first decision: early asymmetry, which was shown to be problematic because this cells are not committed. Another is the polarization model, complicated by the inside-outside model. Speaker says she’s going to propose all three models are correct tomvarying degrees. Aargh, biology is complicated.

Polarity develops at 8 cell stage, down regulation of pars influences these decisions. Also forms outside an inside cells with division at 8 cell stages. Some outside cells divide to make 2 outside cells, others to make one out and  one in..what causes this difference? High cdx2 causes conservyative divisions, low yields differenitiative, so there is a molecular bias. Notnrandom, but not tightly regulated either. Cdx2 also localizes apically as cells polarize. There is a positive feedback loop between polarity and cdx2, maintaining inside-outside polarity.

Second decision of primitive endoderm vs epiblast: random or pre-specified/biased? Used 4D tracking of cells and fate decisions, developing pedigrees of cell fates. First wave of divisions is biased to produce Epi, subsequent waves biased to produce PE — so not random. Salt and pepper pattern is an accident of poorly defined position of blastocyst cavitation.

25% of ICM cells undergo apoptosis! What an inefficient business development is.

  11:30-11:50 Saori Haigo (Graduate student, UC Berkeley) “Global tissue rotation: a novel polarized morphogenetic movement that controls tissue elongation and egg shape in Drosophila”

Flies! New question: how do flies make an ellipsoid egg? It’s another issue of developing asymmetries.

In this case they’re looking at follicle cell epithelium that surrounds the maturing egg. Mosaic mutants in follicle cells can produce round rather than ellipsoid eggs. What are the follicle cell behaviors that promote elongation?

Follicle cells undergo constant, sheet like migration orthogonal to elongation — cool movies of rotating follicle cell layer, at rate of 0.5µm/min. Waaa, I want a confocal microscope of my own!

Round egg mutants suppress rotation. How does rotation cause elongation, though?

Collagen IV forms a polarized fibrillar matrix during rotation. Basically it’s laying down circumferential fibers- a “molecular corset”. The collagen is not oriented/polarized in round egg mutants.

  11:50-12:10 Ankita Das (Graduate student, Univ. of Southern California) “A Bmp-Id2a-Twist1-Fli1a network specifies ectomesenchyme from neural crest”

Ectomesenchyme is important in formation of vertebrate head–they are derived from neural crest, which uniquely forms ectomesenchyme in head but not trunk. How does zebrafish head skeleton (branchial arches) form? What is the signal to make ectomesenchyme?

Markers: sox10, dlx2a. They’re looking for the regulators of these key genes. Some nc cells start expressing dlx2a as soon as they start migrating, suggesting mesoderm may not be source of signal. There is a change in BMP expression as they form ectomesenchyme — down regulation of BMP may be a trigger. Misexpresion of BMP4 causes defects in EM specification. Hi BMP activates sox10, leads to non-EM. As th cells migrate away, declining BMP permits dlx2a expression and EM fate.

Losing Twist1 has similar effect; Twist1 may also promote EM formation. What suppresses Twist1? Another gene, id2a, that is target of BMP4 and in turn supresses dlx2a. Misexpresion  of id2a also produces errors in EM development. They’ve put together a nice picture of the gene circuitry behind specification of ectomesenchyme.

Here we go, I’m attending the West Coast Regional Meeting of the Society for Developmental Biology, and I’ll be intermittently dumping my notes onto the web, so that’s what you’ll be getting today — my sometimes cryptic impressions of a series of developmental biology talks.

This is the early morning session. It’s late in the day for this Minnesotan, though…but beware, that just means I may start flagging this afternoon.

08:30-10:00 Session 1: Stem Cells in Development and Regeneration (Chair: Monika Ward [Univ. Hawaii])

Hey, speakers get lei’ed at the start of their talk! I guess I really am in Hawaii.

  08:30-09:00 Venugopala Reddy Gonehal (UC Riverside) “Systems level dynamics of cell interactions in plant stem cell niches: Live imaging and microgenomics”

Looking at shoot apical meristems and plant stem cells in Arabidopsis. Very cool time-lapse of plant meristems. Cell cycle length of 70-80 hours! Ouch. But still…lovely fluorescent markers of various stem cell niches, and they can examin stecell dynamics in mutants. They are using experimental data as input to mathematical models that they test in simulations. Looked at two mutants: clavata3, a secreted peptide, that leads to over-expansion of stem cells, and wuschel, a homeodomain containing trancription factor, that leads to an absence of stem cells. Increasing wuschel levels leads to expansion of the stem cell domain; using chip assays, they have worked out the response genes in this pathway…and they’re more transcription factors. 

One weird surprise: a gradient of a diffusible transcription factor that moves through plasmdesmata to induce up regulation. I guess it’s a plant thing. I spend too much time in just animal models.

Reddy’s models (shown in some very pretty simulations) can account for the generation of the patterns of gene activity in the meristem, and also accurately respond to mutations in the same way that the live tissue does.

  09:00-09:20 Kate Lynn Jaremko (Graduate student, Univ. Hawaii) “Regulation of developmental competence and commitment during endoderm and neuroectoderm differentiation in human embryonic stem cells”

Looking for ways to induce ectoderm and endoderm differentiation in hESCs, using activin signalling.  She’s giving a nice clear introduction to the concepts of competency and specificity in development. Low levels of activin signaling are required to maintain pluripotency; inhibiting activin promotes  ectoderm differentiation. experiments involve specifically timed exposures to activin or activin inhibitors , followed by examination for markers for differentiation. 

This is straightforward modern developmental biology: tinker with th molecular inputs, look at the molecular outputs, and figure out effective ways to nudge the development of a cell in a direction you desire.

  09:20-09:40 Jonathan M. Riel (Graduate student, Univ. Hawaii) “Functional deficiency of the mouse Y gene Sly leads to sperm DNA damage and abnormal chromatin packaging”

mouse has 50 copies of Rbmyf1a1 on the Y chromosome. They’re  working with a strain of mice with reduced fertility, using ICSI to get progeny. They noticed a significant difference in fertility with sperm from epididymis vs. Testis in mice with deficiencies in NPYq — traced to problems in protamine processing, suggesting that there is an NPYq gene involved in packaging and maintaining sperm DNA. Loss of the sly gene leads to abnormal sperm heads, and this work tests whether it is specifically an sly deficiency that leads to poor sperm maintenance in their mice. Loss of sly leads to a loss of membrane integrity and slightly to severely decondensed DNA condensation.

Conclusion: sly is involved in DNA packaging in spermatogenesis. Ok, I’ll believe him.

  09:40-10:00 Catherine D. McCusker (Postdoc, UC Irvine) “Insights into the establishment of positional information in the limb blastema”

Limb regeneration requires interaction with nerves — they can even induce blastemas by routing a nerve to a wound site, although it won’t regenerate into a new limb. That also requires positional information in the epidermis. The standard model invokes gradual specification by a progress zone in th egrowing limb bud. An alternative is that the full range of proximodistal morphologies are pre specified in the early limb bud.  Pre specification supported by transplant experiments that seemed to show that zones of the blastema had limited developmental potential. Distal blastemas should only be able to make distal tissues, however, new experiments with better markers show that transplanted blastemas can regenerate more proximal tissues. Thes new results suggest that the blastema is NOT pre-specified.

The basal region of the blastema is committed, and transplants will induce duplicated proximal structures.  Apical region of the early blastema does the same thing.  The new model is one of progressive specification of basal cells while apical cells are more plastic — a hybrid of the progress zone model and the pre specification model.

Talk also had pretty picture of lovely stained regenerating limbs. I’m a sucker for nice morphology.

Once upon a time, there was a man who thought rather highly of humanity’s potential. Sure, there were things humans did that were awful — they could be violent, and careless, and short-sighted — but they also did amazing things like science and art that other species didn’t. Overall, he thought that calling someone “human” was a high compliment. And this idea colored his thinking in such a way that it began to shape his expectations of people; maybe we should expect human beings to do more than eat and excrete and reproduce, and maybe we should recognize that the word “human” meant an awful lot more than just a certain flavor of meat or the species of your parents.

He also noticed that every single human being he ever met, without exception, was more than a perambulating set of chromosomes. Some were good at math and others liked to dance and others were kind and yet others liked to argue, and these were the virtues that made them good and interesting, and made them…human, in this best sense of the word. So when he praised being human, it wasn’t for the accident of their birth, it was for the qualities that made being human meaningful.

Unfortunately, not all humans liked having the fact that words carry greater connotations than the most narrow, most literal, most concise, dictionary-style definitions, despite the obvious fact that they all do. They got quite irate.

“I am a human because I am not a squirrel, or a hyena, or a fish, or broccoli,” some said, “and I resent the fact that you think there’s more to me than being a not-squirrel!”

“You expect me to be good at math to qualify as human?” complained some of the slower, less alert people, who failed to notice that the man had made no such specific requirements.

“The only thing that all humans have in common is that they were born to other humans, and can only reproduce with humans,” said other complainers, “therefore, that is all that ‘human’ can imply or mean. How dare you taint my pure and perfect language with complications and nuances and expectations!” 

And the man listened to their arguments for a while, and argued back for a while, and then he came upon a simple solution. He told the not-squirrels and identity-by-rutters and functional illiterates and simple-minded machine-coders to fuck off, and it was good.

“Ad hominem!” they squeaked.

“Who cares what barely human people think, anyway,” he shrugged.

We Gnu Atheists, and atheists of all kinds, are often accused of following “just another religion.”  I’m not particularly fond of the usual riposte — something along the lines of sarcastically pointing out that atheism is a religion like not collecting stamps is a hobby — because I think we sell ourselves short when we pretend atheism is an absence of values rather than a positive and powerful collection of strong modern beliefs, but also because there are distinct differences in the way atheists should think, relative to theists. I say “should” because, often, where I see the starkest contrast is in atheist apologists for religion, who sometimes seem to be unbelievers still trapped in old modes of thought.

Jaques Berlinerbau is one such infidel locked in a medieval mind; he links approvingly to a long-winded, plodding essay by R. Joseph Hoffmann, who reminds me of nothing so much as a pompous clergyman, who has little too say but will puff it up into a good solid tendentious drone ands mercilessly slaughter all of his critics with ennui. They have another old criticism of the Gnu Atheists: we have a shocking deficiency of martyrs.

Say what? We’re supposed to build our movement on corded stacks of dead atheists, preferably ones murdered by torture, or Hoffmann and Berlinerbau will not take us seriously? I can’t think of a better example of the blinkered brains of our critics. Religion, especially Catholicism, loves to dwell on torment and death and finds validation, even, in the agonies of the faithful; why, God must be really, really important if his followers will throw their lives away for him. Hoffmann seems to be impressed with this line of thought, and tries to argue that atheists should grant more credit to the distinguished line of martyrs, often believers, who died to advance the cause of freethought. He thinks we ought to be more appreciative of Bruno and Servetus and Hus and Aikenhead for their deaths in the name of a cause.

Personally, I recoil in disgust at the thought. We should celebrate the lives of good people, not their deaths. Their deaths do not contribute to a cause, they only stand as testimonials to the bloody oppressive nature of our enemies; all would have served humanity better had they lived. We should no more find vindication in the execution of heretics than doctors would revel in the glory of millions of miserable deaths to typhoid and cholera and smallpox and childbed fever — we should want to simply end these horrors. A trail of tears is not a victory parade.

Atheists should not want martyrs, and neither should we desire the deaths of our opponents. Death is an end and a loss and not any kind of virtue, and that Berlinerbau and Hoffmann have these antique fantasies of good godless corpses piling up to lend gravitas to the movement, or that the vocal Gnu Atheists even imagine such a story would be desirable, says quite a bit about their inability to think beyond their obedience to a theological mindset. While they reject the notion of a god, they continue to pay homage at the altar of religious morality.

It’s god to see I’m not alone in rejecting their entire premise. Both  Jerry Coyne and Ophelia Benson express similar sentiments. There really is a coherent and consistent Gnu Atheist consensus that is very different from the horrid old modes of religious thought, and it takes an unimaginative and narrow mind to think otherwise.

I have learned that today is Christopher Hitchens’ birthday. I hope he gets many more.

What is it with all these New Atheist birthdays in the springtime, though?

I have a request to all of you. Some of you hate me, so you’d enjoy this, but it’s more important that those of you who have a mild and distant affection for me take a stand, too. If, sometime in the future, when the billions of dollars role in, if you learn that I’m flying in children for sex, I don’t want you to defend me. Don’t use friendship as an excuse, just come out loud and clear and denounce my behavior, with no qualifiers. Please. There aren’t any justifications or rationalizations possible.

I am not planning to turn into a leering old degenerate, but you never know…I could suffer traumatic brain damage that radically alters my behavior, turning me into either a lecher or a Christian. If such a horrific event occurs, consider me dead and start abusing the bankrupt personality residing in my corpus, OK?

Ditto if I start robbing banks, beating up little old ladies for their social security checks, praising the Templeton Foundation, or become a Mormon. That stuff is just wrong.

Lawrence Krauss has sent me a guest post discussing his debate with William Lane Craig. As he notes, these debates with cranks are always a mistake; debates in general are a format tailored to give the weak side, even the side that has no credibility at all, an equal standing with the stronger side at the beginning, and then the conclusion is resolved by the rhetorical ability of the two opponents, not the evidence. William Lane Craig is an expert debater, but he is otherwise a vacuous moron, but because he has a series of familiar syllogism that he always trots out in these debates, and because his audiences tend to be packed with the kind of people who automatically find any mention of Jesus laudatory, he tends to “win,” i.e., he gets the approval of people who reject the atheist without thinking.

You can watch the whole debate on YouTube. Warning: Craig goes first. You may not be able to stomach it — it’s a confident display of obtuseness. When he isn’t lecturing on Christian ‘physics’ — with Lawrence Krauss right there — he’s throwing out assertions and calling them evidence. For instance, he declares that Jesus’ tomb was found empty…as part of his litany of evidence for Jesus’ divinity. It’s the kind of thing that he can only get away with in front of a friendly audience that will never, ever question the assumptions of their faith.

Craig is much more polished and self-congratulatory than Krauss, and I can see that another irritation here is William Lane Craig’s smug post-mortem and the dishonest distortions of some attendees. For example, the theists claim that Krauss rejected logic in his opening remarks. This is false. What he points out in the beginning is the evidence trumps your preconceived notions, no matter how carefully you’ve worked them out, and that the observations described by physics, such as the rate of falling of two objects of different weights or the results of the two-slit experiment, are not trivially derivable by logic alone, in the absence of evidence demonstrating the phenomenon. The debate was supposed to be all about the evidence, which demands some awareness of the concept of empiricism, and Craig and his acolytes don’t even seem to know what the word means. That the Big Bang occurred 13.7 billion years ago was not determined by a theologian deriving it from his religious principles, or by a physicist standing at a chalkboard and working it all out from pure mathematics — it is a measurement from data.

Also, Craig claims to be using Bayesian logic. No, he is not. Scribbling a few trivial equations on his slides does not substitute for Craig’s painful ignorance of physics.

You can find more thorough, non-religious discussion of Craig’s fallacies at Debunking Christianity.

@JoeCienkowski is a motor-mouthed creationist who hangs out on Twitter. His wife, Brandy Evans Cienkowski, is much less vocal and considers herself one of those ‘liberal Christians’, and she apparently got fed up with Joe (he has also been arrested at least once for battery in January, which is not a good sign) and left him…and then was, presumably, reconciled and rejoined him, at least by Joe Cienkowski’s account. Strangely, Brandy has gone completely silent since this reconciliation, and Joe has has also spluttered to a trickle of tweets, all unresponsive to questions about his wife’s status. This has roused suspicions, and there is a call out for contact. If you know Brandy Evans Cienkowski, let people know here or on Twitter.

The beans have been spilled. I lied. I am not the Digital Cuttlefish, I am not leaving Scienceblogs, I have no talent for poetry, and I am not a nice person.

I am highly untrustworthy, though. I had people asking all day if I was really in Elmhurst and if I was really going to the local pub last night. I’m a little worried that I’ll get home to find the wife has changed the locks on me.