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Corante Blogs examine, through the eyes of leading observers, analysts, thinkers, and doers, critical themes and memes in technology, business, law, science, and culture.

The Press Will Be Outsourced Before Stopped

Vin Crosbie, on the challenges, financial and otherwise, that newspaper publishers are facing: "The real problem, Mr. Newspaperman, isn't that your content isn't online or isn't online with multimedia. It's your content. Specifically, it's what you report, which stories you publish, and how you publish them to people, who, by the way, have very different individual interests. The problem is the content you're giving them, stupid; not the platform its on."
by Vin Crosbie in Rebuilding Media

Travels In Numerica Deserta

There's a problem in the drug industry that people have recognized for some years, but we're not that much closer to dealing with it than we were then. We keep coming up with these technologies and techniques which seem as if they might be able to help us with some of our nastiest problems - I'm talking about genomics in all its guises, and metabolic profiling, and naturally the various high-throughput screening platforms, and others. But whether these are helping or not (and opinions sure do vary), one thing that they all have in common is that they generate enormous heaps of data.
by Derek Lowe in In the Pipeline

Disrobing the Emperor: The online “user experience” isn't much of one

Now that the Web labor market is saturated and Web design a static profession, it's not surprising that 'user experience' designers and researchers who've spent their careers online are looking for new worlds to conquer. Some are returning to the “old media” as directors and producers. More are now doing offline consulting (service experience design, social policy design, exhibition design, and so on) under the 'user experience' aegis. They argue that the lessons they've learned on the Web can be applied to phenomena in the physical and social worlds. But there are enormous differences...
by Bob Jacobson in Total Experience

Second Life: What are the real numbers?

Clay Shirky, in deconstructing Second Life hype: "Second Life is heading towards two million users. Except it isn’t, really... I suspect Second Life is largely a 'Try Me' virus, where reports of a strange and wonderful new thing draw the masses to log in and try it, but whose ability to retain anything but a fraction of those users is limited. The pattern of a Try Me virus is a rapid spread of first time users, most of whom drop out quickly, with most of the dropouts becoming immune to later use."
by Clay Shirky in Many-to-Many

The democratisation of everything

Over the last few years we've seen old barriers to creativity coming down, one after the other. New technologies and services makes it trivial to publish text, whether by blog or by print-on-demand. Digital photography has democratised a previously expensive hobby. And we're seeing the barriers to movie-making crumble, with affordable high-quality cameras and video hosting provided by YouTube or Google Video and their ilk... Music making has long been easy for anyone to engage in, but technology has made high-quality recording possible without specialised equipment, and the internet has revolutionised distribution, drastically disintermediating the music industry... What's left? Software maybe? Or maybe not."
by Suw Charman in Strange Attractor

RNA Interference: Film at Eleven

Derek Lowe on the news that the Nobel Prize for medicine has gone to Craig Mello and Andrew Fire for their breakthrough work: "RNA interference is probably going to have a long climb before it starts curing many diseases, because many of those problems are even tougher than usual in its case. That doesn't take away from the discovery, though, any more than the complications of off-target effects take away from it when you talk about RNAi's research uses in cell culture. The fact that RNA interference is trickier than it first looked, in vivo or in vitro, is only to be expected. What breakthrough isn't?"
by Derek Lowe in In the Pipeline

PVP and the Honorable Enemy

Andrew Phelps: "Recently my WoW guild has been having a bit of a debate on the merits of Player-vs.-Player (PvP) within Azeroth. My personal opinion on this is that PvP has its merits, and can be incredible fun, but the system within WoW is horridly, horribly broken. It takes into account the concept of the battle, but battle without consequence, without emotive context, and most importantly, without honor..."

From later in the piece: "When I talk about this with people (thus far anyway) I typically get one of two responses, either 'yeah, right on!' or 'hey, it’s war, and war isn’t honorable – grow the hell up'. There is a lot to be said for that argument – but the problem is that war in the real historical world has very different constraints that are utterly absent from fantasized worlds..."
by Andrew Phelps in Got Game

Rats Rule, Right?

Derek Lowe: "So, you're developing a drug candidate. You've settled on what looks like a good compound - it has the activity you want in your mouse model of the disease, it's not too hard to make, and it's not toxic. Everything looks fine. Except. . .one slight problem. Although the compound has good blood levels in the mouse and in the dog, in rats it's terrible. For some reason, it just doesn't get up there. Probably some foul metabolic pathway peculiar to rats (whose innards are adapted, after all, for dealing with every kind of garbage that comes along). So, is this a problem?.."
by Derek Lowe in In the Pipeline

Really BAD customer experience at Albertsons Market

Bob Jacobson, on shopping at his local Albertsons supermarket where he had "one of the worst customer experiences" of his life: "Say what you will about the Safeway chain or the Birkenstock billionaires who charge through the roof for Whole Foods' organic fare, they know how to create shopping environments that create a more pleasurable experience, at its best (as at Whole Foods) quite enjoyable. Even the warehouses like Costco and its smaller counterpart, Smart & Final, do just fine: they have no pretentions, but neither do they dump virtual garbage on the consumer merely to create another trivial revenue stream, all for the sake of promotions in the marketing department..."
by Strange Attractor in Total Experience

The Guardian's "Comment is Free"

Kevin Anderson: "First off, I want to say that I really admire the ambition of the Guardian Unlimited’s Comment is Free. It is one of the boldest statements made by any media company that participation needs to be central to a radical revamp of traditional content strategies... It is, therfore, not hugely surprising to find that Comment is Free is having a few teething troubles..."
by Kevin Anderson in strange
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

The Loom

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December 24, 2003

Mad Cow Memories

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Posted by Carl Zimmer

I can already see the grim look many Americans will have as they chew on their Christmas roast tomorrow. They'll be thinking about yesterday's report that a cow in Washington state tested positive for mad cow disease. There's some comfort in knowing that so far it's just a single cow, and that American cattle are regularly screened for bovine spongiform encephalitis. The grimmest look this Christmas may be on the faces of McDonald's shareholders and cattle ranchers. A single Canadian cow that test positive wreaked havoc on the entire beef industry up north. But this Christmas also brings a fascinating discovery about the bizarre agents that cause disorders such as mad cow disease: they may actually record our memories.

The work comes from the lab of Eric Kandel, the Columbia University neuroscientist who won the 2000 Nobel Prize for medicine. Kandel got the prize for figuring out some of the molecular underpinnings of memories. Each neuron has one set of branches that send outgoing signals and another set that receives incoming ones. These signals can only jump from one neuron to the next if an outgoing branch nuzzles up to an incoming one, creating a junction called a synapse. Kandel studied how the neurons in a sea slug change as memories are laid down. (These are obviously not memories of the Proustian sort--just simple associations, such as the memory of a shock coming after the flash of a light.) He showed that new synapses are created and other ones grow stronger as memories form. Kandel also identified a number of the molecules that seem to be responsible for strengthening these connection. (His Nobel prize lecture makes for good reading.)

Kandel did not rest on his laurels, but immediately tackled some of the big questions about memory that he and other neuroscientists had yet to figure out. A neuron may have tens of thousands of synapses, but only a few of them may change as a memory forms. Yet the instructions to make proteins that cause this change come from a neuron's single bundle of DNA. If the nucleus gets a signal to form new synapse-strengthening proteins, how do the proteins go only to the right synapses. And, even more importantly, how do those synapses stay strong for decades, when proteins themselves live only a short period of time?

Kandel and his coworkers reasoned that a memory-forming synapse must get some sort of "synaptic mark" that tagged it for synapse-strengthening proteins. They then looked for molecules that might be responsible for the mark. As they report in the December 26 issue of Cell, they have discovered what may well be the synaptic mark in a compound called cytoplasmic polyadenylation element binding protein (CPEB for short). CPEB can be found in cells throughout the body, but they found a special form of it in the neurons of sea slugs, and then later found it in fruit flies and mammals. They found that CPEB is synthesized during the earliest stages of memory formation, and probably drives the production of molecules that physically lay down new synapses and tells them where to grow. Evidence suggests that the protein can do this by "waking up" dormant RNA molecules in the synapse. (RNA is the messenger molecule that carries copies of genetic information to the protein-building factories of the gene.)

To understand how CPEB could do all this, the researchers looked closely at its structure. That's when they had a shock: CPEB has much the same structure as the agent that causes mad cow disease.

Mad cow disease is infectious, but it's caused not by a virus or a bacterium. Instead, it's caused by a rogue protein called a prion. The normal version of the protein (called PrP) may do a number of jobs in the body, and seems particularly important in the brain. But sometimes a PrP gets a funny kink in it and folds into a new shape. This new prion then bumps into a normal PrP and forces the normal copy to take on its own strange shape. The prions clump together and force others to join them in Borg-like fashion. Mad cow disease can spread if cows eat feed that has been supplemented with other cows--in particular, if the feed contains prions. Humans eating those sick cows can take in the prions as well and get a fatal brain disease of their own called Creutzfeld-Jacob disease.

Prions were the object of scorn and skepticism for years, in part because they were so different as pathogens from viruses or bacteria. Prions had no genetic material, and yet they spread like genetically-based pathogens. Eventually the evidence became too much to ignore (and also won Stanely Prusiner of the University of California at San Francisco a Nobel of his own). But prions were revolutionary in another way that most people don't know about: they enjoy a unique kind of evolution.

In the early 1990s scientists realized that yeast contain prions. These aren't mutant PrPs, however, but two completely different proteins that just so happen to have the ability to change shape and force other proteins to clump with them. Unlike mad cow prions, yeast prions don't necessarily harm their hosts--in fact, they actually make yeasts thrive better than without them. And since yeasts are single-celled, they can pass down their prions to their offspring. (A prion in your brain won't get down to your sperm or eggs, so you can't infect your kids.)

In other words, a yeast can inherit prions from its parents, despite the fact that it has inherited no prion gene. This non-DNA based inheritance is a lot more like what Lamarck was talking about than Darwin.

Kandel and his Columbia team joined forces with an expert on prions in yeast, Susan Lindquist of MIT. Together, they inserted copies of the gene for the synaptic mark CPEB into yeast so that they could experiment on them and see whether they were in fact prions. They found that indeed, CPEB can exist in two different states. In one, the protein roams the cell alone. In the other, it forces other CPEB to change shape and form clumps with it. They also found that only when it takes on its prion form can CPEB bind to RNA.

The researchers propose a simple but elegant hypothesis for how prions can build memories. They suggest that certain signals entering a synapse can trigger CPEB to become a prion. As a prion, it can wake up sleeping RNA in the synapse, creating proteins for strengthening it. It also keeps grabbing other CPEB molecules and turning them into prions as well, so that even after the original prion has fallen apart, others continue to do the job. The neverending power of prions, in other words, is what keeps our memories alive.

In a commentary in the same issue of Cell, Robert Darnell of Rockefeller University says that if this work holds up to scrutiny (if it's replicated in neurons rather than yeast, for one thing), it will prove "nothing less than extraordinary." It would be extraordinary enough if memory proved to be based on prions, but the finding--along with the earlier work on yeast--raises the possibility that prions actually do a lot of important things in our bodies, and that we cannot understand them unless we are willing to let go of our vision of life as nothing but genes creating proteins. That may not make this Christmas's roast any tastier, but it should help revive the low reputation of prions.

Comments (5) + TrackBacks (0) | Category: Brains


COMMENTS

1. Richard Glen Boire on December 24, 2003 01:04 PM writes...

Stock in McDonalds falls, as Memory Pharmaceuticals (Eric Kandel's co.) files to go public. Initial value = $85 million!

http://www.forbes.com/personalfinance/retirement/newswire/2003/12/23/rtr1190424.html

Permalink to Comment

2. Chevalier on December 28, 2003 11:58 PM writes...

OT: You've posted earlier that 'Soul made flesh' wouldn't be published untill January 6th. I've picked up my copy at a Barner and Noble a few days ago. Fascinating stuff so far.

Permalink to Comment

3. Anthony on January 13, 2004 07:56 PM writes...

I have been reading in the news lately that meat is safe? Hunh????

Meat is safe? That’s a good joke! Meat promotes health? That is an advertisement from industry or from Dr. Atkins (and other quacks) who promoted a terrible diet by selling books and products to the gullible. If you think animal products are safe, consider the following:

What animal products do to people:

Promote--

Cancer

Heart attacks

High blood pressure

High cholesterol

Strokes

Arthritis

Bursitis

Osteoporosis

Flu

Obesity

E-coli

Mad Cow (CJD in humans)

Salmonella

Allergies

Acid Reflux

Cellulite

Chronic Fatigue Syndrome

Diabetes

Headaches

Graves Disease

Cirrhosis

Diarrhea

Anemia

Insomnia

Dementia and other mental problems

Emotional problems

Increase costs related to medical care

Increase taxes to aid poor people who come down with medical problems

What animal products do to the environment:

Use up massive supplies of fresh water. (ex. 5000 gallons to make one pound of beef). Lake Ogallala, an underground reservoir larger than Huron that took millions of years to form shall be dry in 2 to 3 generations in order to irrigate crops to feed to live stock.

Use up massive amounts of land to grow grain. (80% of the grain grown is fed to livestock)

Manure pollutes the land and the water with nitrates and pesticides with other poisons. (livestock in the US outweighs people by 5 to 1)

Pollution from nitrates kills off other wildlife that keeps the Earth in balance.

Clear cutting of rainforests in order to graze cattle.

Stripping away of top soil so that neither grains nor trees can grow in some areas.

Using up energy including fossil fuels in order to transport and refrigerate animal products.

Neither list is by any means complete!

Permalink to Comment

4. M. Simon on March 10, 2004 09:37 PM writes...

B. Lutz at the Max Plank Institute has foud out some interesting things about pain memories in mice:

The decay rate of the memories is genetically controlled.

Permalink to Comment

5. M. Simon on March 10, 2004 09:39 PM writes...

Anthony,

You are forgetting one of the most important properties of meat:

Properly prepared it tastes really great.

People
Eat
Tasty
Animals

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