Friday, January 9, 2009
Recipe: Project Meat Glue
Anyways--back to your regularly scheduled blog post:
Lab protocols are very similar to recipes, but as one of my fellow lab members pointed out, "You don't get to eat anything at the end."
-list of ingredients = cells, proteins, reagents
-cookware = equipment in the lab: all sorts of machines and incubators and such
-directions = protocol for doing the experiment
Much like cooking, if you are making something you have never made before (even if someone else gave you the exact recipe) you might have troubles the first time. Maybe it's the humidity. Or your cells weren't "happy" (industry slang for stressed and low on nutrients). Or maybe you added ingredients in the wrong order unintentionally. Either way, there is a lot you have to do before you can even get started in the lab, hence the fact that my "working in the lab" this week is actually me reading lots of papers, doing lots of internet searches, and preparing an introductory powerpoint presentation for a lab meeting in two weeks. This has to include a background, as well as things like specifics about what you are adding and doing.
For project meat glue, the first step is working out the ingredients, and that requires oodles of database searches, looking for exactly the right flavor of what I need...then deciding which equipment is best and going through with things. All with the help of the other folks in lab - in this case, when you are learning, there are never too many cooks in the kitchen.
Yup...science = recipe.
Boston Restaurant Guide
Below are the restaurants where I have eaten here in Boston, as well as a bit about each of them:
Anna's Taqueria (MIT, various) - filling and cheap.
Au Bon Pain (Kendall, various) - kind of like Panera. Good but gets expensive...
Bartley's Burgers (Harvard Square) - all of their burgers are named after political figures--it's really cramped, so don't go with too many people. Sweet potato fries are yummy.
Bertucci's (Central Square and others) - the rolls are like CRACK. Otherwise, it's like Olive Garden but better food.
Blu (Downtown Crossings) - the meal I had in the cafe wasn't great, but the food in the restuarant is supposed to be superb..it's in the health club of a hotel, so it's not somewhere expected, but it has gotten great reviews
Cabot's (suburbs) - ice cream is better than the food...really elaborate and awesome death by chocolate creations!
Central Kitchen (Central Square) - great local food. Pricey. They used heirloom tomatoes that they had bought at the farmer's market a block away.
Cheers (Faneuil Hall) - overrated - but I'm glad I got to go with my mom and take a picture of her with her Cheers mug :)
Christina's Ice Cream (Inman Square) - bigger portions than Toscannini's, and both their sorbet and ice cream is wonderful. Bostonians are ice cream snobs, so most places here are quite good.
Daedalus (Harvard Square) - lovely rooftop garden. Wonderful salads.
Dim Sum (Chinatown) - go with someone who speaks Mandarin. Otherwise your experience just won't be as good.
East Coast Grill (Inman Square) - LOUD. but fantastic seafood...and the sangria is to die for.
El Pelon Taqueria (Fenway) - cheap and filling.
Emma's Pizza (Kendall) - deliciously quirky pizza. upscale and yummy
Excelsior (Boston Common) - really expensive, but great for Restaurant week - they even brought out a large piece of dark chocolate with "Happy Birthday, Bridget!" on it in delicate white icing, with a small candle molded to the plate with icing. Celebratory without obnoxious singing...loved it! Also, it was louder than most fancy restaurants are, and their wine cellar is awesome (you come through it on the elevator to the second floor where you eat)
Fire and Ice (Harvard Square) - "mongolian bbq-style" - For someone who has had, you know, semi-real Mongolian BBQ (thank you, Khans!), this was terribly bland for me. But the $10 all you can eat Monday night student deal really feeds college guys quite well
Flour Bakery (near South Station) - amazing sticky buns. Call ahead to reserve yours...they sell out quickly!
Four Burgers (Central Square) - sells beef, turkey, salmon, and veggie burgers, and you add toppings...fun but $10 a burger. I met the owner - super nice guy
Herrell's Ice Cream (Harvard Square) - it's in an old bank, so they painted the safe to be aquarium-esque! Very cute!
Kelly's Roast Beef (Revere Beach) - have the beef sandwich or the lobster roll. So good!
Koreana - (Prospect and Broadway in Cambridge) - good lunch specials $9ish
La Famiglia Giorgio (North End) - HUGE portions of pasta. And students get a 20% discount. Leave room for cannolis (basically, stuff yourself on bread, eat a couple bites, and bring the rest home...I had enough for three meals)
La Verdad (Fenway) - opened by a famous chef. Because he wanted to have a taco store. Bring friends and get the chips and guacamole. An order is $7 (as much as your burrito) but totally worth it. Oddly enough, guacamole tastes amazing with parmesean cheese.
Legal Seafood - (Kendall and others) - super expensive, but the seafood here is top shelf. I personally loved the crabcakes, but lobster is also delicious.
Miracle of Science (Central Square) - the menu is on the wall in a periodic table. You can tell you're near MIT when...food really isn't that good. But the name is priceless.
Modern Pastry (North End) - beautiful cannolis. Have three.
Olive Tree - hello $2.85 falafel sandwich with lentil soup! Go early and be served by the owner's 13 year old daughter in plastic looney tunes flatware. Decor is priceless...wait, it all has prices on it. Even the donkey footstop.
Pizzeria Regina (North End) - people who own it can get kind of cranky...there is usually a line outside (they don't take reservations) - realllllly good pizza.
Pourhouse (Boston, near Boylston and Mass Ave) - half-price burgers on Saturdays...so they cost $3. It's usually hard to find a table, and they have no one in charge of seating, so it's kind of a dog eat dog experience. If you're not up for smushed elbows or being pushy, don't go.
Punjabi Dhaba (Inman Square) - cute store with Bollywood playing while you wait. Best bang for your buck, and it's all served on these classy tin cafeteria trays. Make sure to get naan, and a lassi if you're feeling thirsty.
Rialto (Harvard Square) - absolutely amazing. Tuna tartare was beyond delicious - and while food there is pricey, it is doable for the $30 prie fixe meal during restaurant week.
Royal Bengal (Central Square) - good buffet
Sagra (Davis Square) - great Italian for a first date.
Shilimar of India (Central Square) - also a good lunch buffet
Sunset Bar and Grill - the best beer selection in Boston--reasonably priced flights as well. Food is good, too.
Toscannini's (Central Square and others) - mmm. I like ice cream. A lot.
Upper Crust (various) - excellent large slices of takeout pizza. Sometimes they have steak on their pizzas, but it's a lot of unconventional ingredients
Places I want to go:
Hungary Mother (Cambridge)
The Beehive (Boston)
Pho Republique (Boston)
Persephone (Boston)
Toro (Boston)
Plus many many more for restaurant week...you can bet I'm saving money for it now!
Wednesday, January 7, 2009
The Transglutaminase Project - code name "Meat Glue"
-it was discovered in a study of blood clotting factors in 1968
-it is used by food chefs as a bonding agent for proteins
Ajinomoto Food Ingredients
Since this enzyme is a common one, it is isolated using a fermentation process, and you basically sprinkle it on different meats that you want to bond together. It's really popular in the "molecular gastronomy" field - the people that make nitrogen-frozen strawberries for desserts and use blow torches a lot.
-In patients with celiac, gluten comes into contact with transglutaminase and the enzyme modifies the gluten. This reaction causes an elevated immune response that is poorly understood, but the results are the synthesis of far too many antibodies that tell the body transglutaminase is toxic and must be destroyed. Thus, in celiac patients, they are lacking the ability to digest gluten, and the immune response causes inflammation in the digestive system which also hampers digestion as a whole, glutenacious or not.
-use as a surgical glue and tumor treatment is being investigated
So what does this have to do with malaria, you ask? Well...even I really don't know yet. But the really interesting part of this enzyme is that it has a drastic conformational change that occurs with the addition of calcium and a given substrate (think gluten as as example)
So...the best way that I found to think about these two enzymes is using the "Heads, Shoulders Knees and Toes" game. Red is the head, orange is the shoulders, green is the knees, blue is the toes. Thus, when the enzyme is in "closed" position, the head is really close to the toes, but in open conformation, they are really far away. This is about as dramatic a protein change can get.What is even more important is how close the two ends of the protein are to one another. Many proteins are made of many different parts that are bonded together, but this one is basically one long string of amino acids, which in the above picture is represented by the ribbon and stringy things (fittingly, this is called a ribbon model).
The picture below is more 3D - you can see a bit more of how the molecules fit into space. You can also download a special program that will let you rotate this structure around in 3D space to try and better understand how it works.
However, with this picture, you can't where the protein begins and ends...which is why the lab is excited about this enzyme. If you look closely at the ribbon model, you can see that one end of the protein is actually really close to the other end of the protein when the enzyme is in the "closed" position and really far apart when they are in the open position.
There are some really interesting things we could do with this in terms of making it into a molecular tool, but first I have to do some background research into how the folding and unfolding actually works, as well as how to detect how it is working during an experiment, and if that can be done, see if I can control the movement with some small molecule...as in, instead of the enzyme going back and forth between positions due to enzymatic activity, I would add a different non-related substrate and get it to do the same thing.
First, however, I have to map out some experiments to get things started.
The scientific process
The first step is understanding the basics of our lab. Our goal is to build better and more effective molecular tools in order to help scientists understand organisms that don't follow the expected course. Generally, scientists use a suite of organisms from "least complex" to "most complex" in order to test hypotheses: e. coli, yeast, cells from mammals, C. elegans (a worm-like nematode), fruit flies, mice, rats, and humans. Yet, there are many organisms that don't act exactly like these systems that have been rigorously hacked: we have to engineer new ways to use what we know to come up with a way to solve what we don't know.
One of these organisms is Plasmodium falciparum, better known as the parasite that causes malaria (the red things above are red blood cells, and the crescent-looking shapes are the parasite). I'm going to be posting much more about malaria in the future, but for now it's most important to realize that malaria is a disease caused by a parasite we truly don't understand. They are a black box, and in the last thirty years of research, we've poked holes in this box, but due to the nature of the parasite, we haven't learned nearly enough to affect drug development or disease control of malaria.
Thus, the lab is focusing on engineering biological tools to help study malaria and other nonconventional organisms...which brings you to my project. Due to intellectual property concerns, I am going to have to be a bit vague, but if you ever have more specific questions, don't hesitate to ask.
Wednesday, December 31, 2008
Portion Sizes. Or, how what we learn from our parents follows us for a looooong time...
This happens every night. And this sort of habit is why I have such a horrendous problem with portion sizes. I had no idea that this was far more ice cream than you should ever consume until college. I kid you not. I'm not trying to place blame here...but it is a reality that children will notice what parents do and mimic these habits.
Today I discovered a website that shows 300 calorie portion sizes as they really are ---

It's amazing what browsing through these pictures will do for your sense of awareness of the size of things. They include the dollar bill and credit card to provide a sense of scale, something really important to think about when you are learning to control portion sizes.Slightly unrelated but still relevant are the differences between the costs of these different servings. And we wonder why there is such a correlation between poverty and obesity?
Monday, December 22, 2008
Champagne and Sushi Tasting
Courses:
Grilled blue point oysters with green onion vinaigrette
Paul Cheneau Reserve Cava Brut Blanc de Blanc
Hamachi sashimi with spiced strawberry cinegar
Lucien Albrecht Cremant d'Alsace Brut Rosé
Braised stuff daikon (shrimp) with Japanese mushrooms and creamy miso dressing
Lucien Albrect Blanc de Blancs
Sake glazed salmon with green peppercorn-grapefruit vinaigrette
Nicolas Feuillatte Rosé Brut
Broiled eel with apple, pear, and sansho pepper
Nicolas Feuillatte Blue Label
After some deliberation, we decided on the Blue Label and the Cava, together worth about $65 at their prices (I got kind of sad looking at the online prices being much cheaper...but that's Boston for you!)
The gentleman who presented the wines was quite nice as well, and not pretentious in the face of how little we knew about champagne (we were easily the youngest people in the room by about 5-10 years). Also, instead of drinking from champagne flutes, we drank from white wine glasses, apparently because it's easier to taste the flavors, and as you are drinking the champagne immediately, you don't need the same bubble conservation that the flute provides. He also laughed at my use of tin foil to preserve bubbles in unfinished bottles of champagne.
All in all - it was quite a lovely night, and maybe something we'll do again. But for now, we'll be enjoying our two bottles of champagne...
Adventure #1 of Winter 2008 - getting home.
edit: Nope. But keep reading...
I suppose the other part of this story is that I stayed up all night keeping a certain someone entertained and full of apple cider and brie while he was finishing his final exam for discrete math (something with euler circuits and cacti. Nothing I truly understand…). Anyway, his flight out of Logan was at 9 am, so I have been at the airport since about 8 am – I’m glad I am decked out with banana chips, cheerios, fruit leather, hard-boiled eggs, and chocolate chips. Although, it is quite odd to have nothing to do (no schoolwork, that is). Thus, I vacillate between reading old random papers and organizing folders and old documents on my computer (hello report on oysters from age 11) or drifting off in an uncomfortable sleep listening to rather awful holiday music.
Then, in my semi-asleep stupor, I spied a gentleman named Alex in a spiffy winter coat and scarf. Alex is currently a student at Carleton studying biochemistry and theater, and I met him a few summers ago when I worked as a musician in the pit orchestra for Joseph and the Amazing Technicolor Dreamcoat.
He had talked to me earlier about spending some time in Boston this December, but then it came to pass that I would be leaving and he would be arriving on the same day…oops. I called out his name, and he positively jumped out of his shoes. And then we ate at the Wok and Roll (no joke) and talked for awhile as my plane was pushed back even later into the night.
Weather picture one (around 12:30 pm Friday afternoon)
So, I went back to the gate and waited for my 1:25 pm departure time...and the plane was indeterminately delayed. Bad weather in Michigan had stopped our plane from arriving at the gate. However --- hallelujah --- the plane arrived at 5:30 pm. Okay - this is progress. We boarded at 6:15, and got ready to go, the pilots and flight attendants being super generous and staying past their time to get us home. And two hours later, after problems finding a crew to de-ice our plane, the pilots announced that the airport had been shut down. And so...back off the plane.
Weather picture 2 (around 8:30 pm Friday night):
After half an hour waiting in line to get my plane rebooked (and running down my cell phone battery calling the hotline), they announced that the plane was not canceled but rescheduled for the next day at 11:30 am. Good thing, too, because the people that finally got through on the hotline were aggravatingly shouting, "What?! There are no openings until December 23rd? That is absolutely unacceptable!" Our luggage finally returned on the carousel (well, most people's luggage...mine was MIA and there was no one out there to look for it, so I got myself a toothbrush from the luggage office and tried to find food that wasn't Dunkin' Donuts). I had to go over to Terminal C, walk through all of the weird office-y corridors, until wandering enough to find a food court. That closed at 8 pm. Sweet. Okay, so onto the next plan...a bar! I really just needed food, and given my four hard-boiled eggs and cereal menu for the day, I just wanted some vegetables. And boy did they oblige...with rubbery eggplant, nasty tomato, slice of mozzerela, all wrapped ever-so-sweetly on a butter-toasted hot dog bun. Beautiful.
I slugged my way back to the terminal, paid $8 for internet, and spent some time reading emails and catching up...actually, mostly trying to stay awake. At this point I had been up about 40 hours, and I was really dragging. After the airport finally quieted down (two international flights kept things hopping until 2 am), I slept awkwardly on those benches with armrests. Let me tell you --- sleeping to nonstop blaring Christmas music is not my cup of tea, that's for sure. I got up at 5 am, wandered around, and finally talked to the luggage people. Apparently my bag had gotten on the 11 am flight the day before - I certainly wish I had gotten on that flight...I got checked in, went through security, and made my way back to the gate.
The next day: weather picture 3:
The plane was on time, but then it was delayed...again, and again. We had a plane this time, but first no pilots...and then by the time we had pilots and were loaded and ready...the storms were so bad in Minnesota we couldn't take off. Finally, at 5 pm, we took off for Minneapolis, and I arrived in one piece at 7:10 pm central time. Phew. My other bag was just fine, and after waiting outside in the bitter cold, my dad picked me up from the airport and I was home to the snow and loveliness of Minnesota. Woo-hoo!
Wednesday, December 17, 2008
Semester 1: a retrospective
-my new lotion, the olive and aloe ultra moisturizer for sensitive skin from Kiss My Face, makes me smell like bread dipped in olive oil for the first few minutes after I put it on...and I love it!
-despite all indications, the absolute value of my learning in 420 was immense (this is the kinetics/programming/math class). I am really proud of myself. I worked my butt off. And I have never quite had the cards stacked against me like that. Now, granted, this doesn't mean that I passed the course (frankly, I probably shouldn't), but regardless...I did something that I didn't think I could do. Also, props to all of the other BE students who helped me out...you know who you are. Thank you.
-I had a dream once where I was running my own TV show on new science developments - the equivalent of Jon Stewart, science edition. Can I do this for a job? Please?
-biochemistry = da bomb. Mitochondrial pathology, metabolomics of cancer..this stuff is cool.
-watching TED talks while I eat breakfast makes me SOOO excited about the world.
-the concoction of yogurt and brownie mix is delicious
-one of the upsides in living in an apartment is that, even without turning the heat on, my room is always toasty. This is first time in years I have not had to wear two pairs of socks when going to bed, and you can bet I'm excited...
- I really really really want to be able to ice skate in my backyard when I get back - but I understand that this may not happen.
-I love making some dumb biology joke or reference during class and everyone getting it and thinking I'm hilarious. This never happens outside of class, but I'm not giving up hope.
-oral finals are really interesting. You feel like you can never prepare enough, for you have no idea what the questions could cover.
-the worst part about being sick for me is not being able to work out in combination with not being able to think, sleep, or do really anything else.
-I will be taking a two hour introductory class to Alexander Technique this January, and I am so pumped. I need help with relaxing while playing French horn, and this might be just what I need!
-I miss having a tree to decorate. A lot.
-I saw a special on re-discovering the Alexandria of Cleopatra on National Geographic while I was working out tonight, and I was reminded of my fourth grad book report in which I dressed up as Cleopatra and brought a rubber snake to school in a bowl and talked about why I killed myself (and then killed myself by sticking the snake at my throat and falling on a pillow). I cannot believe my mother let me leave the house to be a morose and dramatic Egyptian queen for a project. Actually, I'm pretty impressed in my persuasional skills. Or something like that.
-I could sit and watch glass-blowing for hours. And I would still be just as entranced as when I started.
-I want to be Ms. Frizzle one day. Actually, I want to be Ms. Frizzle + Bill Nye + Michael Pollan + Olivia Judson. All at once.
-I am excited for next semester. Life is going to be great.
Wednesday, December 10, 2008
Article from "Nature"
"A long and happy life?"
The suicide note itself wasn't particularly remarkable.
Handwritten, of course. Even the oldest computers would have detected the quiver in the voice, or parsed the strained phraseology, and automatically alerted the authorities. The blue ink scratched its way across the paper, as if hard pressed to recall the individual shapes of letters. At one point the nib had pierced the white sheet. Few people wrote regularly with pens. It was still taught at school, but the odd love letter or shopping list was as far as most people got. And suicide notes, of course. This was no different; the writing was that of the very old, or the very young.
In a way the hand was old, the oldest that had still lived. But just as the sunrise is as old as time and new each dawn, so this hand was new: three months and twelve days, according to the factory's records.
Even the words, the symbols of the man's thoughts, were not worthy of note. They would have won no literary prize; inspired no doomed, romantic quest; enquickened no tired and demoralized army. The very human story was the usual one: of love, of ennui and, ultimately, of heartbreak.
No one, least of all himself, remembered quite when or how he had lost his first hand, more than 300 years ago. The accident was recorded, but if the loose-leaf binder still existed, the cheap ink was long faded into obscurity. Sometimes he claimed it was an explosion in a fume hood; at other times a gas cylinder had fallen from its moorings and crushed him.
What his memory was clear on, and what was attested to in the medical literature, was that he had attached ('single-handedly, haha!' he would joke) an artificial limb to the remains of his own arm. Not a simple prosthetic, but a fully functioning organ of composite fibre, ceramic joints and golden threads carrying two-way nervous traffic. The body's own electrical impulses provided power to the tiny servos that drove the slender titanium flexors and extensors.
No accident, the second prototype: it was tested and retested, planned months in advance. His wife directed the operation, and when he woke, his right arm to the shoulder was fully robotic. A fortnight later, while he was still delirious from antibiotics and analgesic, she was killed by a drunk-driver.
The record shows that he opened a new lab with venture capital, employed three dozen scientists and disappeared into his research. The exclusive clinic followed: he himself was its first patient, walking out on legs of alloyed titanium — and straight back into the lab.
Half a dozen more clinics started up across the nation, opening their doors to anyone whose medical insurance would pay the fees. For ten years the company replaced natural limbs with artificial constructs that were functionally equivalent to the original. More than equivalent: these never wore out, never got cancer, never got tired, never felt weak or cold.
For ten years the clinics operated and the lab researched. No papers were published, no patents applied for, and investors grew nervous. Interest waned. Two clinics closed; a third of the research staff was laid off. Rumours circulated, created by and lost in the noise of the Internet. It was another three years later when, finally, a press conference was called on the lawn of the first clinic, the handful of journalists who bothered to turn up were turned away — — and were called back, to face a man who under crepusculine clouds glistened.
The patents and the papers followed on the morrow: the artificial blood, the fuel cells, the intricate and minuscule fibres and vessels and motors: in short, a body wonderfully and fearfully man-made.
Only his face appeared natural, and over the following years even that was slowly replaced. Having no need of food, depending solely on a defined and especially formulated medium, protected by filters and powered by the elements, no toxins could threaten him. With hard, durable alloys and man-made composites in place of bones and tissues, redundant systems and every organ replaceable, he was all but indestructible.
Alzheimer's had been cured by the time he reached 105, and the last bastion of mortality — the uncontrolled cell division leading to legion neoplasms — tamed a few years after that. And then he was a living brain in a metal and plastic shell, talking, walking and living: never fatigued, immune to all disease, the Tree of Life incarnate.
For 200 years he lived like this, never needing to eat: a weekly cocktail of nutrients and pharmaceuticals keeping the one, irreplaceable fleshly and uniquely human organ alive.
When the end came it was without fanfare or press conference. No papers were written, no patent lawyers notified. With the finest of Torx drivers he opened an access panel, removed a wire, took out a power cell, held it — his life in his own hands.
The suicide note of the world's first immortal ended simply enough:
I cannot live without her.
-rpg (nom de plume of a molecular cell biologist and hopeless romantic at the University of Sydney)
Nature 456, 836 (11 December 2008) | doi:10.1038/456836a; Published online 10 December 2008
Wow.
Monday, December 1, 2008
Wedding Gifts + Holdiay Consumerism
Then, yesterday I came across this posting in Apartment Therapy Los Angeles (which has a long convoluted name for a blog that is basically a home design blog all about improving your surroundings - lots of pretty pictures, lots of interesting ideas, and it's especially good to give you a sense of what is possible in any given living space). It lists some ideas for wedding gifts which the couple will be able to actually use that are particularly amenable to my age bracket...we want to give something that the couple will like, but all we can afford on the registry is napkins.
Weddings are hard - registries are almost a necessary "evil" these days, and people assume that yes, you're going to need something, or celebrating starting a life together requires the gift of a blender or these steak knives or these very specific tablecloths. I think there has got to be a better way.
My first roommate this year, Elaine, and I talked about weddings for almost two hours, and one of the things she described was the nature of gift-giving in China. According to her, it would be completely unacceptable to give one of your cousins less than $2000 for a marriage gift. And if I was very close to said cousin, the gift should be closer to $3000. If you cannot afford that kind of gift, you do not attend the wedding and reception. Period. Elaine said that some young adults her age go into debt because they can't afford to attend all of their friend's weddings.
This shocks me. I cannot understand why in the world celebrating marriage became so dependent on money and consumerism. It distresses me, I guess, that some people give more thought to the gifts they will receive rather than celebrating something so special and full of love.
And this goes for all holidays as well: if you are, for example, an uncle/aunt, the best gift you could give would be of your time. Instead of toys, give your niece/nephew an entire day, just between you and them. (bonus gift for the parents as well). I can't tell you how much more I remember and appreciate a tradition with my aunt to go downtown and look at the Dayton's holiday exhibit compared to a Target gift card.
Anyway, what follows is a list of some ideas for newlyweds (many are also applicable to your friends for other times of the year and not just wedding-exclusive). And I understand that things break down for different couples and the relationship you may have with them: - gifts are not one size fits all. You know your friends - their likes and dislikes, and what they would most appreciate. People are different, and not everyone will appreciate the same thing.
-give them the gift of flowers - give them a gift certificate for flowers in their new home.
-become "part of the wedding" --- make the cake, do the flower arrangements, play music for the ceremony, make some sort of dessert, fold napkins artfully, make name plates on the tables, etc...everyone has some sort of skill that can be utilized in the whole beginning to finish project that is a wedding.
-if they are moving to a new city and don't know anyone who lives there (but you do), give them a map of said city and do some research on restaurants, places to see a concert, etc... so they can start feeling at home in their new city.
-if they love pets but won't be able to keep a pet in their apartment, make a donation to the Humane Society in their name.
-breakfast in bed/tea tray - completely indulgent, but can be really fun. You can find these at home stores like Marshalls for a decent price, or thrift stores (these can be refinished or repainted as well, if you're crafty)
-if you are giving a gift as a couple and live nearby, give the gift of "sitting at home watching the game with the boys" and "going out shopping with the girls" - obviously, this would be tailored to the couple in question. Bring snacks and watch a movie with one, or bring ingredients to make cookies, or go out for drinks with the other, etc...make it a gift of time to spend with the other person.
-give them a tree (rainforest, taiga, park-related - there are lots of online sites to donate flora and fauna). There is also a fun family tradition to begin which involves planting a tree whenever a child is born so you can watch the child grow with the tree.
-my mother clued me in to the idea of buying decorative plates (with snowmen, santas, etc...) and some ornaments or cookie cutters as something that they can share for their first holiday season in their new home. This isn't something "essential," true...but it is something that will be used if it is there. You can also put a greeting on the bottom of the tray with permanent marker, something to the tune of "Congratulations X and X! --Your name, 2008"
-surf the site Etsy.com - it has lots of homemade and beautiful gifts that are often inexpensive. Also, you can go in together on gifts..if there is a group of you (say, for example, you were close to three other people on your high school soccer team) -- you can come up with a gift together.
-my aunt frequently makes quilts (not for the novice sewer, to be sure, but if you can -- it's a gift that will be used)
-plants (if they like plants -- given the harried nature of most weddings, you may want to just give a card and say you'd like to buy them a plant for their new home, and in their first month or so, make a date to go and pick out a plant (and have coffee or something similar - it's a good way to catch up on their lives as well)
-get together with a bunch of college and/or high school friends and put together an album (either old-school with photos or using a program from the web) of pictures from that time in their life - artsy pictures of campus, plays, dances, football games, parties, etc...you can also personalize it and have old teachers and friends put in memories about their time at school.
-one point that the article (and many of the comments) brought up is that some people actually NEED the things on the registry, and getting anything but that is wasteful and rude, basically the cardinal sin you could do at a wedding, and you end up with lots of stuff you don't want because you decided to be more "thoughtful." I'm torn on this one: I guess buying something inexpensive from the registry and then making it more your own works best in that instance: for example, you could buy a cookie sheet and oven mitts and include some of your family's favorite cookie recipes.
-a favorite board game from high school or college
gifts for parents:
-if your parents have a lot of their photos only in "picture" form, consider digitizing them for archival purposes
-same goes for a home inventory - if you're feeling brave, consider photographing and setting up a home inventory for insurance purposes - it's one of those things that everyone knows they should do, but never get around to
-offer yourself up to do whatever they ask with no complaining for a day
-bake cookies for the holiday season - all their favorites. And then put them in the back of the freezer so they have something to snack on in January
-wake up on a snowy morning and shovel the walk/driveway
gifts for siblings:
-shirt.woot.com = gold. $10 a shirt - each is offered only that day, so check back frequently. Some are odd, but they're a great deal.
-do their chores
-take them to matinee movies, and make a contest to see who can smuggle in the most food