Regions of rapidly evolving genes: evidence of genetic control of the rate of adaptation and disorders of evolution

About four weeks ago I wrote about the possibility that "autism" and "schizophrenia" might be "disorders of evolution". If the genes that code for brain function are experiencing very high variation levels, and thus rapid adaptation and differentiation (evolution), it's plausible that we'd see a range of disorders related to maladaptive variations.

Back then I thought the post was a bit daring, the sort of thing that might cause some in my vast readership to think I was being a bit eccentric.

Nowadays though, that post seems pretty mainstream:

Mouse study finds hotspots of genome instability (John Timmer)

[Nature 10/28/07] ... The data suggest that certain parts of the genomes are "hotspots" that both undergo change frequently, and produce changes that are well-tolerated by the organism. These hotspots undergo changes up to 10,000 times more frequently than quiet areas of the genome, and can undergo multiple, successive changes. The fact that the organism appears to tolerate these changes isn't due to an absence of genes in the CNVs. In the 18 mentioned above, there were a total of 43 genes, including some involved with reproduction, immunity, and brain function.

There's been an idea floating around for a while that suggests that genomes evolve to the point where they work well with evolution. A genome that, by chance, winds up with genes that are sensitive to dose effects in a region that's stable is more likely to be be inherited. In the opposite case, where different doses of a gene might help an organism adapt to different environments, having that gene located in an unstable area might be selected for. The new data doesn't directly address this proposal. But it does find that there unstable areas of the genome that are likely to undergo major changes within the span of less than 100 years, which seems to be a prerequisite for the proposal to be taken seriously.

It turns out Timmer has at least one other post relating these types of gene rearrangements to autism.

I'm ready to be that within six years medical students will consider a wide variety of neuropsychiatric disorders to be "disorders of evolution". You'll have a jump on those whippersnappers ...

How to Hyperlink: advice and some hypertexual history

Coding Horror has done a nice job summarizing the art of the hyperlink -- and he provides historical context:

Coding Horror: Don't Click Here: The Art of Hyperlinking

...I distinctly remember reading this 1995 Wired article on Ted Nelson and Xanadu when it was published. It had a profound impact on me. I've always remembered it, long after that initial read. I know it's novella long, but it's arguably the best single article I've ever read in Wired; I encourage you to read it in its entirety when you have time. It speaks volumes about the souls of computers-- and the software developers who love them.

Xanadu was vaporware long before the term even existed. You might think that Ted Nelson would be pleased that HTML and the world wide web have delivered much of the Xanadu dream, almost 40 years later...

I recommend the article, though every rule should be broken on occasion. Sometimes I do resort to "click here", for example.

The historical context led me to dredge up old links, and in honor of Ted Nelson, I've created a "hypertextual thread" (tag) called "xanadu".

As CH tells us, Nelson was in fact quite unhappy with how the Web developed. In 1988 (yes, that long ago) Ted Nelson delivered the keynote address to the American Medical Informatics Association (AMIA) on "Project Xanadu" -- and it was clear he wanted the web to go away.

That was the most fun and interesting keynote I've ever heard at AMIA, but half the audience thought Nelson had gone off the deep end long ago. AMIA has since been careful not to invite anyone particularly novel to speak.

Nelson wasn't the only hypertext pioneer to be unhappy with the unidirectional hyperlink. Berners-Lee, the "father" of the web, used to be very unhappy with our fragile hyperlinks. I recall he'd wanted a directory service and an indirection layer for the hyperlink, his CERN experiments simply escaped prematurely. Nowadays, of course, Google is beginning to offer suggested redirects when one enters a failed link into the search engine -- an unimaginably brute force solution to the problem. I'm sure there are some interesting lessons in how this has evolved!

For a bit more on the topic over the past few years (I used to write about this pre-blog):

• Computers and thinking (shades of Vannevar Bush)


• Jakob Nielsen on reviving advanced hyperterext - Nielsen wrote a book on hypertext @ 1995 -- it's a great guide to a lot of forgotten innovations


• Hyperscope: a failed experiment by Doug Engelbart, who sometimes calls himself the inventor of hypertext (with some legitimacy)
  


• The NYT Magazine on "the universal library", the post mentions Dickson's hypertext science-fiction classic "The Final Encyclopedia". Dickson pretty much pegged wikipedia.

The scandal that created the army and executive privilege

I can see why this story is generally omitted from this history books:

Making Light: Retreat Along the Wabash

It was the worst defeat under arms ever suffered by the US Army. Out of some 1,100 men who answered muster on the night of November 3rd, 1791, only 27 were unwounded at sunset on the 4th. 90% were dead. The camp followers, the artillery, all were lost.

In just over three hours on that bloody morning St. Clair lost 60% of all the men then under arms in the service of the United States...

...And that, my friends, is why Fort Wayne, Indiana, is called “Fort Wayne” rather than “Fort St. Clair.”

That too is where we got a standing army, and where the doctrine of “Executive Privilege” comes from.

Among other things, we discover Washington was quite human.

Ground zero in Pakistan: Informed Comment blog

Talking Points suggests Informed Comment: Global Affairs: Barnett Rubin as a source for understanding the global crisis of the week (month? year? decade?) -- Pakistan's crisis of governance.

I glanced at the most recent post and it felt good. Consistent with what I'd already understood, plausible details that extend what I've read in known reliable sources, a measured tone.

I'll be tracking it.

This is also an opportunity to thank the gods that Rumsfeld is gone and, though Cheney and Bush remain, the rest of America's military and political governance is in far saner hands than it was a year ago.

Karen Hughes: another Bush loyalist quits

I missed this one: Bush loyalist Karen Hughes has quit. She was on a bizarre mission to improve America's image abroad. That's a bit of a tough job while the President works to make waterboarding a competitive sport.

Surprisingly, from what we all remember of the bizarre debut of her mission, Kaplan tells us she was actually doing a good job resurrecting the corpse of America's cultural outreach. He doesn't really have any good explanation for why she abruptly quit.

Did she finally give up on George Bush Jr?

Wives for China: yet another crisis

Dyer on China's demographics: "...Girls are in such short supply that it is estimated that by 2010 there will be 37 million young Chinese men with no prospect of ever finding a wife."

A Chinese wife, specifically.

The usual solution to an excess of young males is to go to war. That doesn't scale in today's world.

The alternatives are either polyandry, finding a nation with an excess number of females, or an innovative technological solution.

In the meantime China should start cash subsidies and guaranteed free education and healthcare for all female children. China needs to make girls dramatically more attractive to parents.

I like Bob Herbert

Why Is Bob Herbert Boring? is an impressively mean and obnoxious article in the Washington Monthly. I suspect Mr. Herbert is more likely to read that column than to read this blog post, but the essay was so nasty I'm obliged to say that I like Mr. Herbert's columns and I read every one he writes.

Maybe it's my dour Scots nature, but I don't mind that Mr. Herbert belongs to the evidence-based community. Heck, I read Paul Krugman religiously (including his blog) and he's no flaming ball of cheer.

There are snappier writers, but it's all relative. Mr. Herbert writes in an elite field -- it's no shame to be "very good" rather than "great" in that crowd. His special value comes from his clear vision and his dogged determination to talk about people most readers of the NYT may prefer to forget.

So Mr. Herbert -- don't be discouraged. Maureen Down is disposable, you are not. Keep writing.

How long is your to do list?

This Google gadget appears at the top of their iGoogle Gadget Directory: "ToDo Gadget, easily manage and track your daily to-do list. ToDo gadget lets you add up to 7 tasks, the average amount of concurrent tasks the human brain can handle effectively".

Seven.

I clearly do not belong in the same world. I think I'm running at about 300 between home and work ... [1]

[1] I don't manage my work by my inbox. I use tasks.

NYT's new ads: drive me to Adblock Plus

Advertisers are their own worst enemies. The NYT has introduced a new set of obnoxious interstitial ads that float around the screen then settle in place hiding text. They have to be manually dismissed.

Which means I've installed Adblock Plus.

I was ok with old style ads, but the new ones have pushed me over the edge. Now I won't see either.

A stupid move by advertisers - and the NYT.

Williams College: a word of praise

A combination of unearned good fortune and inspiration born of desperation allowed me to spend a half-year at Williams College playing liberal arts student. The academics were much less work than what I was accustomed to, and the teaching was superb. Best of all, my real undergrad institution paid the whole thing -- room, board, travel and tuition. (Actually the best est part was a I got academic credit for having fun. [1])

I have a soft spot for Williams, but it's fantastically expensive for people who have to pay. So I credit them for enabling some students who are very smart, and perhaps only somewhat poor, to go there ...

I am very pleased to announce that, in consultation with the Board of Trustees, the College has decided to eliminate loans from all financial aid packages and replace them with grants....

This move is the latest in a series of steps the College has taken in recent years to ensure that a Williams education is affordable...

Previous steps had reduced the amount of loans we expected financial aid students to take. For students from families with the lowest incomes that expectation has in recent years been zero. But other financial aid students had been expected, depending on income, to borrow cumulatively over their four years $3,800, $7,800, or 13,800.

This move also comes at a time when the College has succeeded in increasing the socio-economic diversity of entering classes. In fact, the Class of 2011 is the first in history to have more than half its members qualify for Williams-based aid. Even more have won scholarships outside the College..

I don't think this would help much kids like mine though -- it's state school for them. (They've got their share of advantages anyway.)

If you're on the edge of middle class or below, however, and a good student, I would encourage a look at Williams. Even back in the day there were enough non-rich students there to offset the weird experience of studying next to the ultra-rich.

[1] Of course for me learning is fun, so it's not like I wasn't goofing off completely.

Perfect commentary on the million terrorist watch list

Last week more stories appeared about the dysfunctional "watch list" maintained by the FBI's unchecked civilian contractors.

I've written about this many times. Anyone who's ever sat through a med school course on positive predictive value knows what this sucker is worth.

The good news is that the list has gotten so large that even the world's dimmest investigative agency must be starting to suspect something has gone wrong.

The bad news is that when we get rid of it, the Bush administration will replace it with something at least equally stupid.

The other good news is that the situation is perfect for Morford's patented "over the top" prose:

Behold! The Bliss Watch List / To hell with the FBI's million-strong Terrorist Watch List. Here is your killer alternative

.... In fact, if my rough estimates are accurate, at the current ridiculous rate of growth, the terrorist watch list will hold roughly 87 billion names by, say, your next birthday. It will soon list every single person on the face of the planet, along with all dead people, the unborn three generations out, and (strangely) many plants. It is just that insidious. It is just that absurd and obscene and just that much of a hint of the nasty surveillance state we are quietly, viciously becoming.

Great read. Humor is good.

Islamofascism; the greatest threat ever

I can't add anything to Krugman's comments here:

Fearing Fear Itself - Krugman New York Times

... "And Mike Huckabee, whom reporters like to portray as a nice, reasonable guy, says that if Hillary Clinton is elected, “I’m not sure we’ll have the courage and the will and the resolve to fight the greatest threat this country’s ever faced in Islamofascism.” Yep, a bunch of lightly armed terrorists and a fourth-rate military power — which aren’t even allies — pose a greater danger than Hitler’s panzers or the Soviet nuclear arsenal ever did...

The Party of Bozo indeed.

iPhone progress: pretty darned slow

My crummy Palm Tungsten T/2 is failing fast -- the power switch has died (a known design flaw) and the LiOn battery is good for about 3 hours (died within a year of purchase). It crashes frequently and is, really, an awful thing. Palm deserves to die.

The Palm world is pretty awful, but I hate my RAZR more.

Wouldn't it be nice if I could replace both of 'em, and not have to carry an iPod around too? What a great idea!

Yeah. The iPhone. Gee, I almost forgot about that #$&^@# thing.

Problem is, the iPhone is making very slow progress on my "most have" and "nice to have" iPhone demands. Let's check the list (updates in bold):

Non-negotiable:

1. Copy, Cut, Paste: No progress
   
2. Search: No progress
3. Tasks at least comparable to the 1994 PalmPilot tasks: No progress. Task sync was supposed to be in 10.5 but was dropped.
   
4. Synchronization with Outlook at least comparable to the modern Palm OS (in other words, flawed, but useable). A 256 character limit on contact comments is not acceptable. No progress.
5. Run FileMaker RemoteL No progress, except a rumor that FileMaker is abandoning FM Remote completely.
   
6. Synchronize notes. : No progress. Dropped from 10.5
   
7. Multi select and process for email. : No progress.
8. Apple needs to fix the "international problem". It's ridiculously easy to run up a $1000 phone bill unintentionally when outside the US. The phone needs to provides a permission-only control over non-US EDGE access. Fixed.
9. Enable iPhone Bluetooth tethering, so a computer can use it to go online. (added in honor of Boingo). No progress.

Wishes, not demands:

1. A real calculator. No progress.
2. Flatten the recessed headphone socket. No progress.
3. Site-selective synchronization - so can sync at both work and home, but not send home data to a work machine. No progress.
4. Support for a bluetooth keyboard and mouse. No progress.
5. Video out - so I can use a larger display. No progress.
6. Encrypted data stores. No progress.
7. Third party app support (signed is ok). There's a promise of some kind of development environment, but it's not clear it's Cocoa based. Apple is adding data storage and more UI power to WebKit, but that doesn't help me much if the app can't work with tasks, calendar items, etc.
   
8. Flash support, but not from Adobe. No progress.
9. GPS No progress.
10. Custom ring and alert tones: Available now.
    
11. Allow file storage on the iPhone. No progress.

Of the nine critical items, only one has been addressed so far and one (FM Mobile) has had a big regression. It's plausible of course that Apple will add the task/note synchronization to 10.5.1 or 10.5.2 by next February.

Of the 11 "nice to have" items there's resolution of one and we might see something on another some day.

The iPhone I am willing to buy probably won't be available before spring 2008.

Deep sigh.

So what about the Blackberry and Windows Mobile?

The geeks I read tell me that Windows Mobile is even worse than the Palm world. Hard to believe, but I trust 'em.

So that leaves Blackberry, but I'm an OS X fan. BB is basically an Outlook extension. I'd prefer not to be tied to Outlook forever.

I think I'm going to have to buy another crappy Palm device. I'll buy exactly what I have now to reduce the pain.

Image of the week: Fallows in Berlin

James Fallows visits a minor Berlin museum.

I definitely want to visit Berlin. Definitely a glass-half-empty and poisoned kind of place, which suits me of course.

Fallows took a photograph from one of the museum exhibits. I won't try to describe it, but it really must be seen. A thousand words indeed.

LinkedIn joins Google's open social networking

The great thing about a closed ecosystem taking the #1 position is that the best option for rivals is to collaborate around an open solution.

That's the best option, but it rarely happens. Usually rivals simply fight it out. Remember Sun and Netscape? In the 90s the two could have collaborated to fight Microsoft on the browser front, instead they fought bitterly. Netscape died, Sun was mortally wounded, and IE ruled (still does).

Google might be smarter with OpenSocial:

BBC NEWS | Technology | Google opens up social networking:

...Google said that around a dozen social network partners had signed up to the system, including business site LinkedIn, Friendster and Google's own social network Orkut...

I bolded LinkedIn because it's the social face for one's corporate self. A unique front with few challengers. I'd expect Google to invest in them if they haven't already.