For a long time, I looked forward to every conference I went to. I engaged as much as I could and felt like I intellectually bloomed at them. Then I got pregnant. A malaria conference I really enjoyed the previous year was scheduled for May- exactly when I was starting to Really Show and feel awkward. I went and had a miserable time. The Carebear brought up the pregnancy to people to excuse me going for an extra dessert. Which bugged me on many levels. So then we fought about that, creating enormous stress and tension generally. Walking around downtown was exhausting; I never felt more disabled (which, in a way, is a testament to the good health I should be grateful for, but is also a more honest presentation of pregnancy than is usually given). I had something like a panic attack in the surge of bodies pressing toward lunch (like sharks after chum, I tell you. Crazy scientists). I couldn't muster the courage to talk to a neat genomics guy I'd met before. And I'm pretty sure I let my professor down and embarrassed him with the freaking out. So it was pretty awful.
This conference (Scion10) I was sure, would be different. These were diverse, fascinating people, some of whom had assured me online they were interested in actually meeting me. I felt excited, and a bit nervous. However, I was ready to go and be myself, which I'm not usually able to do in scientific contexts, not since all the drama my first year in grad school. Or at least I was ready to go and be one authentic version of myself (if not my least formal and inhibited self, certainly an honest one).

Yet this conference did not feel right. I left feeling incredibly out of place and like I needed to stuff my self back into a broken shell. I did not meet many new people; I mostly spent times with the ones I already knew comparatively well, staying in my comfort zone. Though, eventually, I was pushed out of it abruptly and in a way that startled me. I realized how fragile and tenuous relationships can be. Particularly when they depend on a 'status' of being on someone's inner circle.
The sessions did have quite a few bits of neat info, and some of them may percolate in my subconscious and hopefully I'll have something interesting to say about them at some point. However for now I am am weary and stressed.

It doesn't take a talent to be mean, your words can crush things that are unseen

For amusement:

Blink 182 I won't be home for Christmas
"Outside the carolers start to sing
I can't describe the joy they bring
because joy is something they don't bring me"


SouthPark version of the Dreidel song
"Cortney Cox, I love you, you're so hot, on that show"

The Muppets sing 12 days of Christmas
"Five gold RIINNNGS (ba dum dum dum dum!)"

Hugh Leonard Christmas Countdown
(cannot find link! Alas!)
"11 partridges accompanied by 12 pear trees"

Adam Sandler Hanukkah Song
"eight crazy nights...
OJ Simpson- NOT A JEW"
(I think this one got played every year on Loveline)

They Might be Giants Santa's beard


To satisfy my inner hippie:

Peter Paul and Mary Light one candle
"Don't let the light go out
Let it shine through our love and our tears"

Dar Williams The Christians and the Pagens
"finding faith and common ground as best as they were able"

John McCutcheon Christmas in the trenches


Joni Mitchell River
"I'm so hard to handle
I'm selfish and I'm sad"

I have no idea why:

Dan Folgelberg Same Old Lang Syne
"Just for a moment I was back at school
I felt that old familiar pain"

Gayla Peevey I want a hippopotomus for Christmas
"Mom says a hippo would eat me up but then
teacher says that hippo is a vegetarian"

The Vandals Oi! to the world

Faith Hill Where are you Christmas?

And not holiday so much but so appropriate this time of year:

Linkin Park My December
"I'd give it all away to have someone to come home to"

Counting Crows Long December
"and there's reason to believe maybe this year will be better than the last"

They Might Be GiantsNew York City
"It's snowing, it's snowing, god I hate this weather
Now I walk through blizzards just to get us back together"

So I was not on the agenda for Toastmasters this week, alas! Actually, it was good, because that just meant I got to do a good Tabletopic, and since we had an 'extra' speech I even got to fill in as evaluator. I am gearing up to participate in the evaluation competition this spring, and the more evaluations I can get in the better. Last year I deeked myself by going 5 seconds overtime. I think it was subconscious self-sabotage of not wanting to compete with my awesome Toastmaster mentor. Yes, that's it. Couldn't be because I'm long-winded, oh no. Perish the thought! Anyway, I love doing evaluations. I'm not completely sure why, but I have some (not mutually exclusive) hypotheses as to why:
1) They are the only form of extemp speaking in Toastmasters, and that is simply something that my mind is particularly good at. Any speech in which I had a basic default structure, a topic, and 5 minutes to prepare would be enjoyable for me. I even liked extemp way back in 4-H competitions as a kid. Extemp is wonderful because I don't have the same oppressive expectations I can build up around a prepared speech- a bit of lack of polish is completely acceptable. Yet, it's better than true impromptu (like Tabletopics), because I actually do have a moment or two to think and organize my thoughts.
2) I just like telling people what to do- in that '"ooo I have authoritah!" slightly power-hunger way. If I ever develop any people skills maybe I would enjoy being a manager (I've previously lamented that it seems like most PhD's career trajectories end up management. Perhaps that's only if you want 'career advancement', but it seems common in both academia and industry. I don't know if management per se is bad, but the PhD process is horribly backasswards training for it and it wasn't where I thought I was headed for by going this route).
3) I just like telling people what to do- in a really good way. An evaluation that is any good leaves someone with both specific aspects to improve upon, and the motivation for doing it. Generically, people like doing what they are good at. So finding the best parts of a speech to highlight is both a positive upbeat thing, and an intrinsically important part of motivating people to improve. The evaluator as motivator is also why delivery/attitude is important in the Toastmaster's context, a very good thing for me to practice. I apparently come across as perky at Toastmasters. On one level, I am highly distressed by this, although "upbeat" and "energetic" sound good. (but... perky? Really? Maybe it's just my ideiolect, but that is not an appropriate description of Sciencelizard).

In addition to the evaluation, we had TableTopics with an appropriately motley assortment of questions. The question I got was what my crystal ball shows for 1000 years in the future. I decided to go for the future I hoped to see, which looks something like this:

• Nation-state identity (read: patriotism) will be obsolete. I'm thinking about the idea of group identity affiliations being basically all voluntary, and mostly intentional. I've long ago accepted people will always want to "otherize" someone- I just hope to see it limited to the content of one's character. Defining identities -your own and other's- via nationality, or any other attribute you are basically born into, is fraught with perils. On the other hand, judging people's identities (like "doucheweasle") for people based on voluntary groups (like "Yankees fans") is probably never going to go away, and is comparatively more reasonable to work with.
• The notion of corporation will go the way of the dodo. Intentional economic structures and intentional communities, FTW!
• Technology is always fun to speculate on, what I'd most 'look forward to' would be what amounts to a Google brain implant. I want to be able to look at something, or hear music, or an accent, or even a taste, and be able to look up what it's called or who wrote it, or where it's from, or what the ingredients are. We're getting shockingly close in some ways, just not directly (e.g. we're building ways that data-input, like audio input in the microphones built into the iPhone, that more or less replicate our sensory input- I just want to skip the extra step).

Random side note about the conversation in lab going on right now: "Ni ge CD8 T-cells" sounds really weird.

Google search: "Blogs are..."
Google suggestion box "blogs are like sharks"

“Exotic medicines and spices could be obtained. Knowledge could be traded. Jews were even available.”

"Bra burning activists and other unicorn-like creatures."

Dearest Invitrogen:
19 rounds of experimentation. 19 rounds of inconsistent, marginal, fickle knockdown of MFG in macrophages.
But this time...these cells may not have been happy; they did not respond well to the old reagent. I did not have high hopes.
I was lost.
But now I am found. Because I have RNAiMAX, and it knocked down MFG, to levels I could not even detect. Instant KO !!! ZOWIE!
Not only that but I obtained these results the very first time I tried RNAiMAX. And I somehow had the wisdom to knock down enough cells and stimulate them to test cytokines. So I have samples to collect data from; data that I should be able to trust. Oh sweet, benevolant Invitrogen, my most sincere thanks. You are my savior and my very most favorite company, ever.
Love,
ScienceLizard

P.S. Thank you for helping me have data for lab meeting so as to not look like a complete F-up (for once).

I'm the jokemaster today. I hate being the jokemaster. I'm awful at being funny on purpose.
Anyway, here is the joke for today (shamelessly stolen [albeit modified] from some site with annoying popups that I nonetheless link to out of a misguided sense of honesty):
A woman brings a 2 and a half month old baby in the doctor's office.
After arriving, she is taken to the examining room and waits for the doctor.
The doctor comes in and asks "How are things going?"
The woman says "Well, we're a little worried. He doesn't seem to be gaining much weight"
The doctor says "Well, take off his clothes and let's check". The doctor gently and thoroughly examines the baby, tickling him and making him smile. Finally, he puts him on the baby scale, and the doctor checks the growth charts. "Yes, he's only in the 10% percentile. That is a bit concerning. Is he breastfed or bottlefed?"
The woman replies "Oh, breastfed!"
The doctor says "Well, strip down to the waist"
The woman removes her blouse and bra and sits on the examining table.
The doctor starts gently and thoroughly examining her breasts, kneading and pressing them for quite a while. He finally looks up at the woman and says "No wonder he's not gaining weight, you don't have any milk!"
The woman grins and replies "Of course I don't. I'm his aunt!"

Today's seminar was on the correlation between genomic regions of low copy repeats and autistic spectrum disorders. It was given by a classical genetics guy, who was working with good patient population DNA samples.
He started off by framing these low copy repeat (LCRs) regions as "the dark matter of the genome"- drawing some parallels about the difficulty in detecting them and their importance in evolution (as dark matter does not emit radiation/is difficult to detect, and is important to the evolution of the universe). It's not a bad metaphor, but not overly illuminating (yes, I just said a dark matter analogy wasn't illuminating- sue me).
These LCRs are most likely a pretty important source of inter-individual heritable variation. Where they rank in comparison to single nucleotide polymorphisms (SNPs) and epigenetic factors is currently a matter of debate, but humans have quite a lot of these (relative to mice, at least). A better analogy put forth is that- if SNPs are changes in letters in the book of life (i.e. the genome) then LCRs are changes of whole sentences or paragraphs (potentially duplicated, deleted, inverted, or even moved around from one page to another [inter-chromosomal translocations]).
Autistic spectrum disorders seem to have a respectably large genetic component (e.g. for monozygotic twins, autism appears in both at a rate of 60-80%), but it's not like there's yet a single gene to explain things. However, they have now linked regions with LCRs to autism (and schizophrenia). There are numerous candidate genes in these regions, some of which affect known neurological pathways (like glutamate metabolism, or cholinergic pathways). Overall, it looks like there is an increased length of duplication in certain LCR regions in schizophrenics and autistics.
Yet the situation is not as simple as "inherent weird LCRs, get disease". It seems that it's usually the case that related individuals do not have the same LCR differences that autistic individuals do. One possibility is that there is an underlying mutation that makes one generally susceptible to LCR variation (a gene that increases replication fork stalling would be a good candidate; since it's possible lower throughput through LCR regions [where DNA replication tends to get tripped up] would result in hotspots for slippage-based mutations).
To anyone with a cancer research background, this thinking has a certain reasonableness to it. It's known that you need to get multiple mutations to get cancer (I seem to remember that in mice you require at least four separate pathways get altered, and more in humans). Given cellular protections against cancer such as redundancies in cell-cycle checkpoint pathways, robust DNA repair and apoptosis, and the known rate at which mutations occur, it should be relatively hard to accumulate sufficient mutations through random DNA hits (at least on the timescale of a normal human life). Instead, what may be happening is that there are some key genes that you can hit that subsequently make more mutations much more likely (this is called the mutator hypothesis). So the notion that some genes could be 'mutators' for autism, by producing higher frequencies of LCR variation, is an appealing way to explain the seemingly contradicting facts of high heritability with no specific gene linkage.
As to why getting weird bits of your genome with more or less copies might produce neurological conditions in particular... well this gets back to the fact that humans have a lot of these highly variable regions. It's highly speculative, but it could be that relatively rapid cognitive/social neurological evolution in higher primates (which have high LCR variability) is a result of a relative density of genes that influence cognition and social capacities in our LCRs.

This professor had a rather engaging speaking style, but was a touch overly-colorful. His repetition worked well for emphasis, but he kept asking himself questions and answering them in really exaggerated tones ("I'm a fly guy. Do I believe in model systems? UhhhHUH!! You bet I do!"). Much better than the kind of speaker that puts me to sleep, but slightly comical.

I talked to him after the seminar and he mentioned some cool things he had done with flies. Apparently, the tubular sclerosis pathway is well mapped, and conserved from flies. It connects to the TOR pathway; there's some promising use of rapamycin in treatment*. He told me they had made a mutant that recapitulates the cellular/neuronal aspects of the disease and found that they could completely rescue it by decreasing calorie consumption by 75%.
I immediately responded "So what's the plan? Screen kids at birth for autism genes and starve the ones that have it?"
He looked really alarmed. "I didn't say that!"
I need to work on my sarcasm projection.


*And we all know what that means, right? Say it with me now! Activation of autophagy will prevent autism!! /pet autophagy obsession

So one of the reasons I set this account up was to have a place to put the random stuff that I feel I need to write up following a conversation that occurs elsewhere on the intertubes. May I present, food tidbits, random snipets of yummy knowledge I've got rattling around my brain.

(For when “eat food, not too much, mostly plants” is not quite enough detail to tell you what to do with your cuboard…)
A few notes on foods and processing:

• Kidney beans are actually the same species (Phaseolus vulgaris) as many other beans identified as distinct culinary items (pinto beans, black beans, navy beans). All can contain phytohemagglutinin (a lectin glycoprotein!), but kidney beans can have them at especially high concentrations. To make sure your kidney beans safe to eat, soak them for a number of hours before cooking (I’ve heard at least 5, but it’s easiest to do overnight in a bowl in the refridgerator) or ensure they reach a sufficiently high temperature (e.g. boiling). If for some reason you want phytohemagglutinin, you can get it through Sigma (catalog number L1668).
• Soybeans have high concentrations of trypsin inhibitors, which will block your digestive enzymes. This can make them very rough on your digestive system if the soy has not been adaquetely processed. There are a large number of ways to make soy digestable, from the practical (e.g. cooking with wet heat) to the esoteric (e.g. using green tea polyphenols). If for some reason you want soybean trypsin inhibitors, you can get it through Pierce (catalog number 20235).
• Broccoli is a cannonically healthy food (right up there with brussel sprouts). Broccoli illustrates a very important nutritional principle- the Goldilocks effect. Mostly, you will hear people extolling the virtues of raw veggies and sometimes talk about how cooking destroys nutrients. On the other hand, as you can see from beans, some processing is not only a good but a necessity. For broccoli, carotenoid antioxidants are increased upon boiling, although the compound sulforaphane (which appears to be a promising chemopreventative agent in) is much more usable in raw broccoli. The best solution is probably to eat both raw and cooked broccoli, but short of that a light steaming- neither too little nor too much, is a reasonable compromise.

And while I'm at it, a few other nutritional factoids from the carcinogeneis and chemoprevention class I took way back when:
Fiber is healthy right? Yet many clinical studies have found ambiguous results when it comes to the use of fiber in preventing colon cancer. My professor thought that what was going on is that fiber helping ‘move things along’ is a good thing for healthy people. However, if you already have polyps, adding too much fiber irritates the digestive track, increasing the inflammatory response and promoting cancer development.

Vitamin A (e.g. betecarotene) is an essential nutrient, and the folkwisdom that you should carrots to see better has some truth to it since the orange pigment of carrots gets metabolized to retinyl, the form of vitamin A needed by the retina. That said, it's definitely a Goldilocks thing: too little leads to blindness, but vitamin A is fat soluble and so too much leads to all kinds of nasty symptoms, including liver failure. Furthermore, carotene provides an important lesson about "antioxidants". The thinking was that carotene would be a useful chemopreventive agent (cancer preventing dietary supplement), until the epidemiological test data came in. It turns out that, at least for smokers (who have altered oxidant/antioxidant metabolism), adding betacarotene increased the risk of lung cancer and death (see publications about the "CARET" trial). The unfortunate truth is, we don't fully understand how compounds can act as pro or antioxidants in various tissues. Which is one reason to regard 'anti-inflammatory' ratings of foods with some skepticism. Particularly when they would tell you to avoid blueberries.*


*In the interests of full disclosure, it should be noted that I LOVE BLUEBERRIES and will simply not accept any 'science' that indicates they might not be good for you.

Something about when the bit toward the end where the lab coat is discarded in favor of whatever-it-is with feathers reminds me of someone.

A Toastmasters meeting synopsis, in bullets.

• Asking the Google for Tabletopics tips = win
• Contretemps is a cool word.
• Being Tabletopics mistress rules, because then you don't have to worry about being picked!
• People will write down very strange things if you ask them to write a secret about themselves.
• The last people you would ever expect spend time dancing on bars.
• Making people laugh is awesome. Going to the grocery store at 1am to get raspberries is sufficiently aberrant behavior to make people laugh.
• Rainbow lizards follow the leader.
• "distressed, depressed, distraught" is a fantastic alliteration.
• It will require eleventy million dollars for me to ever retire.
• Giving evaluations can be hard.
• We've had an average of 8.7 members per meeting. Bob said he didn't know how the .7 of a person snuck in there. I patted my belly knowingly. Did I mention making people laugh is awesome?
• Supposedly, I look like I know what I'm doing up there. WIN. It's a mess from in here. I hope my science is more like that than I realize.