Views of Strasbourg

Scaffolding! Another for my collection.

Sunday morning brought new snow after Saturday's rain washed it all away. At 9 am not much of anyone was out. The botanical garden was closed due to the weather.
Why? The plants are still there.

Not many people were biking around town, either.

This statue seemed quite pleased with the snow.

This other one rather less so.

Some architectural details.
This sort of thing really lends a good look to a city.

These gulls were waiting for something.

This young swan reminds me of Natalie,

seeing an intruder in her territory and giving a good nip.

The passing beaver did escape to the safety of the bank.
There was snow on Thursday, too, and school trips went on as usual.
A few inches of the fluffy stuff didn't seem to bother anyone.

More stories tomorrow!

.

Les Assises, late Saturday

Well, actually I'm behind in my blogging and the meeting is completely over. The poster is back in its tube. My USB stick is gone, forgotten in the meeting's computer after a quick download of rabbit pictures before the morning session. And my camera's memory card didn't record a single one of the photos I took on my walk around Saturday afternoon in the last of the light. You'll never see the sunset over the Rhine. Er, not my photo of the sunset over the Rhine. Possibly I just didn't put the card all the way in its slot or something. Possibly there will be nice pictures of Strasbourg Sunday morning, but it just depends. My train is at half past 11, so if the card behaves there's hope.
.
All that is not the point of this blogpost. It's just the usual messing around convincing you of the painfulness of my life when it's really nothing much. My hotel might be cheap, but it's clean and the mattress is comfortable and I have no loud neighbors.
.
Back to a bit of science.
I mentioned on Friday's post some of what you can do now that you can look at hundreds of thousands of markers in tens of thousands of people. This sort of massive genetic search is being used to work out the genetic contribution of very complex diseases, such as Type 2 diabetes and heart disease and hypertension, which have multiple environmental factors and yet a clear genetic influence.
.
Type 2 diabetes genes are big treasure these days, and many huge international consortia are searching them out. One of these studies was presented to us on Friday, where they took a good many people (I didn't write down all the details, but they're in the paper) with T2D or with a particular insulin & glucose level response 2 hours after eating a meal. They looked at markers over the entire genome to find those associated with an abnormal response. And they found some.
Frankly, if you look at many thousands of markers, you're always going to find something more or less correlated with the anomaly you're testing. If the odds of getting a result at a marker are 10,000 to 1 against (absolutely Fabulous in the world of genes!), for every ten thousand markers it's an even bet you run across a hot one just by chance. So we take the markers that pass the statistical tests with a grain of salt.
.
(I just realised that I've eaten in this restaurant before. I was in Strasbourg 3 or 4 years ago, and we landed in a tiny little place at random, the very day before they were closing up shop to leave on vacation and they were emptying the fridges. What a meal! It was wonderful then and it is now. I was actually thinking about it yesterday, hoping to run across something similar, and here I am - at the restaurant literally next door to my hotel! What threw me off is last time we entered through the door at the other end of the long narrow room, off the parallel street. Just 8 tables. They can seat 25 and that's it. It's Jean-Paul! Every table has a pair of salt-shakers that are unique, like you'd find at the flea market. My table has chipped chickens. Across the way it's cats, and next door it's cows in chef's hats.)
.
(The mousse au chocolat that I've just ordered is known as the Small Dog. A sort of Doberman cross. Mmm. I don't really get it either but apparently it's a treat.)
.
Weren't we talking about genes for diabetes?
Ah yes.
Well, some of the candidates involved in glucose metabolism have already been fingered, but they account together for maybe 10 % of the genetic contribution. And those are the best candidates, so you see that now we're looking for little bits.
So fine. The genome-wide screen pointed up a new handful of loci possibly involved.
That means that a marker came up hot; but then they decided, kind of just like that, that whatever gene was closest to the marker must be the important one.
Ummmmm.....
It doesn't always work out that way. Especially now that we know that DNA sequences that aren't genes in the traditional sense can have enormous effects. But the top marker was somehow related to glucose metabolism, so it's easy to be seduced by that connection. They may well be right, but that kind of jump can take you off on a wild-goose chase, and when you eventually throw out the result as spurious, you're so sick of it that you're not likely to go back and look for a different explanation for the initial result.
.
(As yes. The dog connection for the chocolate mousse. It's served on a plate... Three large spoonfuls... sort of spread out....It's just as well he makes the joke in advance.)(It is really good, though.)
.
What really bugged me about the study, though, was their strategy for continuing. They decided that a gene really involved in diabetes must increase in RNA expression in response to a meal.
Well that's just silly. It's well known that the level of RNA made for a given gene can have relatively little correlation with the level of protein that is made, and still less with how active that protein is. (DNA codes for genes, which are copied into an RNA intermediate, and the RNA is translated into the protein, which does the actual work the gene is known for. But each RNA molecule can be read many times, and the protein itself can be more or less stable depending on conditions. Proteins also move in or out of cells, or change their compartments, or acquire a phosphate group, or etc etc in response to a stimulus.) So the researchers had this a priori idea that a role in diabetes had to necessarily pass through an increase in RNA in order to have anything to do with it. And when the RNA level didn't budge two hours after a meal, they decided that meant it was just another red herring.
Hey!
I wasn't enamored of your skip in the chain of evidence above, but if it really is a logical candidate, there's no need to be so hasty about tossing it in the dustbin!
.
The point here is: just be careful about what you're doing. Mind those fixed ideas about how your new gene "should" behave. You're there to discover how it behaves, not to document your preconceived ideas. Mind the chain of evidence as well. If a clue leads you to the middle of a street, you can't just pick the prettiest house as the right address, even if there is a sign in the window saying Please Come In.
.
Um. Strike the loud neighbors thing. Just for tonight, there is somebody playing the piano on the other side of the wall. Not part of the hotel, so it’s harder to yell at them. It’s decent playing, but it just goes on and on.
.
Pictures tomorrow.
Really!
Though if you just can’t wait, there are already a few over at Pink Rabbit Abroad.
.

Strasbourg, the Hotel.

Registering rather late for this meeting, I didn't even bother to lok up the hotels suggested by the organizers. Those are always full and they're never the most economical. The CJP has a pretty stingy ceiling for housing costs; they barely pay for the cheapest box along the highway; you can expect to pay a good chunk of the bill yourself, in spite of having to work all day away from your cats and comforts of home. So I look online for something affordable and walkable in Strasbourg. A trick combination, because 'affordable' in the center of the city often means a tiny, elderly building with minimal insulation and dubious plumbing. The photos on the websites are like figures in scientific journals - prettied up and carefully cropped to present only the best. Don't you believe for a second that it really looks like that every day.

Anyway.

I spun the wheel and came up with Hotel 21st.

It's the least expensive to offer free wifi (that is, really, wifi already figured in the bill) and also have a room for four nights. A lot of decent-looking places were just full.

Also, it's walking distance from the station and two blocks off the historic pedestrian district. My room is on the 5th floor (American counting), conveniently offering me a modicum of daily exercise.

First order of business, this wifi thing. Their system requires a password. Fine, but my computer refuses to connect. Something about an IP address not being recognized. The computer in the lobby won't connect me to my email either, with the same error. I'd look into it, but the meeting I'm going to is providing connected computers so I take the easy route and just wait for it to start. I'm so darned lazy sometimes it's unbelievable.

Second order: a shower.

Eh... one of those bathrooms where the shower corner is meerly curtained off. The floor slopes uncomfortably toward the drain, which, ALAS, has a huge plastic thing around it, curling up at the edges, smack under the shower head. It's an art to avoid stepping on it.

This is not such a surprise. Any cheap hotel near an airport has just such a bathroom.

What's totally new is the soap. Not that it's liquid soap in individual plastic envelopes absolutely impossible to open with wet fingers. But that it's scented soap with a unique flavor: green beans.

Yes.

I swear.

Green bean soap. Big stringy woody overcooked green bean-smelling soap.

This is precisely why I have odds and ends of diverse hotel soaps floating around in the depths of my toiletries bag. Just In Case.

On to sleeping. I have two pillows. A foam brick so thick it gives me a sore neck, not to mention crushed ears. Then a limp sack of granular material that is just icky. What works is covering the sack with a double layer of towel, which gives it some needed thickness and evens out the bumps, and a layer of t-shirt for smoothness against the face.

While the interior has been redone, this is indeed an old building and they didn't splurge on insulation. The little heater in front of the window might think it's 21°C in here, but that must be a very local measurement. More than a meter away it's downright cold. Turned way way up, it gets livable.

The view out the window is nothing much, just the facing row of buildings. Most of the windows have their shutters closed, in that incomprehensible French thing for closing up tight and Dark. One window I can look into. It's directly across from me, one floor down. Hard against the window and facing it is a large bed covered with fluffy comforters, in which a woman sits and reads or types on her computer. If she looked up she'd see me watching her. The three days I'm here so far, she's always there, propped up in bed, no matter what hour I pass by and give a look.

.

So that's my hotel. Tomorrow: back to the meeting.

.

The Assises de Génétique!

It's a fun little meeting, held every year in a different city, where French geneticists of all persuasions (meaning, I suppose, that cytogeneticists and somatic geneticists and epigeneticists are just as welcome as the usual one-gene-one-illness kind) gather to present and discuss the latest.

I haven't gone to all of them, but I did get to see Angers and Montpellier and now Stasbourg this way, and for a smallish meeting that covers a lot of scientific territory there's a lot of interesting science around.

.

This year one of the things in style is the deciphering of the genetic components of complex disorders. As a cancer researcher myself I was particularly interested in one of the talks in the opening plenary session, on the genetics of lung cancer.

.

(OMG that is one astounding onion soup! And an interesting beer to go with it.This is not a high-class restaurant I've chosen to dine and write in, with its plastic menu and paper placemats, but the first course is great. It's not your usual dark brown beefstock onion soup with a layer of bread and cheese on top, but something lighter with white wine, no cheese, and bread on the side.)

(Why am I dining alone? Well, I meant to meet up with friends at the Welcome Cocktail, but for some reason they planned that in a space meant for 300 people. After letting in 450, they started turning us away, and I wasn't among the lucky ones, having arrived independently just a bit late. Like 20 minutes after it started. How 'late' is that for a cocktail party?)

.

Getting back to science. Cancer is many things, and can be divvied up in many ways. One of the main ways is genetic vs environmental, with breast cancer being the poster child for hereditary risk (though less than 10 % of cases are strongly hereditary), and lung cancer sitting on the other end of the seesaw as the classic environmental disease (stop smoking! Now! All of you!). In fact, it has long been suspected that there are genetic factors that contribute to lung cancer. The effect of smoking is just so strong that they've been hard to identify.

Modern molecular biology to the rescue: Now that we can screen many thousands of markers in many thousands of people, gathering up 50,000 lung cancer cases and looking at markers across the entire genome is doable in a reasonable amount of time.

And they found stuff.

'Natch.

In Europeans, three loci (literally 'places in the genome', which usually correspond to genes, but don't always) are significantly associated with the risk of developing lung cancer. One of these was already known. Two are new, one at the tip of chromosome 5 and the other on chromosome 15. On chromosome 15 there's a cluster of genes around the marker that turned up hot, all of them components of the nicotine receptor in the brain. And it turns out that the hottest marker is a little change in one of these that makes it bind nicotine just a little bit better than the usual version.

Makes perfect darned sense!

People with this variant version experience greater dependence on nicotine than people without it. If they take up smoking, they're much less likely to be able to kick the habit. Doesn't mean they can't, but it's a significant handicap. Gives all the meaning to antismoking campaigns that lean on Don't Start.

So these people with the variant smoke more and for longer and expose themselves to more tobacco carcinogens. It's a gene that works _with_ the environmental factor. Not one or the other, but both together. (Just to be fair, having the variant does increase lung cancer risk for people who don't smoke, but its big clinical importance is in smokers.)

This only goes for Europeans. The variant is quite common in Europe (34 % of chromosomes there have it), but is not seen at all in Asians or Africans. Something else must be going on with them.

.

This is just the tip of the iceberg of gene-environment interactions. It's been several years now that the Nature vs Nurture arguement has been shown to be a false dichotomy in almost every domain. High-throughput gene screens on huge cohorts are beginning to give us the details.

.

Going to Strasbourg

It's always nice to get on the train and go. Especially a nice new comfy train that's not too crowded. Some of the trains they have serving Clermont-Lyon are real relics, should be taken to Culoz for graffiti and breaking. This one's a good new one.

Our first destination I've been to many a time: Lyon.

I'll have an hour and twenty minutes and the Part-Dieu station. It's the nicer one, with decent shops and coffee & pastry, a major shopping mall across the street and a dozen restaurants all close by. Just perfect since I'll be there right at lunchtime, ready for a hot meal rather than a cold sandwich.

From Lyon it's off to Strasbourg, where I've also been but only once. And it didn't count fully because I saw it with Iris, which meant we saw the insides of the museums and never got a chance to walk just everywhere and see it all in person.

In Clermont, waiting to go. The train is waiting at the quay; no need to get cold outside. I pick the best window, facing forward. People are spilling out of the train across the quay, just in from somewhere. They hurry off to the tunnel and then to work, school, appointments.

Here we go. Gently, without warning but for the clock ticking over to 8:58, we head slowly north.

It's a grey, grey morning. Did the sun come up? It must have by now.

It's cold enough to snow, but hasn't. The crows' nests and mistletoe stand our in the naked trees. Interesting - none of the mistletoe trees have nests, and the trees with nests don't have mistletoe infestations. I wonder if there's a reason for that, or if I just don't have time, for a heavily infested tree, to see that each clump is plant, not nest. Could just be chance, too. If 5% of trees are infested, and 2% of trees have crows, then only one in a thousand should have both, just at random.

Past Roanne, fields dusted with snow. Closer to Tarare the patches in the tree-shaded gullies are big enough to gather snowballs. Then back to grey.

Rolling through the stark and shivering countryside there are not many crows about, just a few picking at the leavings in the cornfields. Plenty of hawks instead, sitting fluffed up in the trees and on poles.

Lyon Part-Dieu station is unheated, as far as I can tell. And why should it be, with all the open stairways leading up to the quays, and people constantly going in and out of the big doors to the street. Happy to be out of the wind and weather, but it isn't warm!

I have lunch at the only sit-down restaurant I don't have to go outside to get to. Yes, it is heated, though there has long been no fire in the generous fireplace along one wall. The restroom, in spite of the code to get in, is full of young women begging and warming their gloved hands under the blower. Over the noise I can't tell what language they're begging in, but it isn't French.

The news lately has been doing a series on pickpockets in France. The footage is mostly from the Paris metro. I'm not the sort to take all my baggage with me to the restroom, though one of my Paris friends certainly would. I have my shoulder bag with me, but the beggar girls remind me of the Bulgarian gangs working Paris and other major cities, making me wonder about my duffel, which contains my computer and my knitting, and not only the irreplacable Maurice but the visiting gecko, Warren. Not to worry - all is in place at my table when I return, guarded by my travel-weary poster tube.

This tube, in fact hasn't travelled all that much. It went by car once from Toulouse to Clermont. Its only major journey has been to Denver, where the airline did in fact lose track of it, delivering it to my hotel in extremis the morning of my poster presentation two days later, covered in stickers and barcodes and black gummy areas where stickers had been removed. One of the orange end parts has been lost, so it's closed on one end with an old TSA notice of inspection and some laboratory tape. What bearer of such a ratty-looking poster tube (the contents, I assure you, are first class!) could ever have treasures worth stealing in a small, cheap duffel bag?

Un dessert, madame?

I shouldn't, but by the clock I've got 40 minutes to go. I say I'll look at the menu, meaning to marshal my resolve and order just coffee. But I remember the coffee here is nasty, and see they have crème brulée...

An excellent crème brulée, in fact, surprising considering the dubious quality of my gnocchi gratinée.

The restaurant has quite filled up since my arrival. Everybody else is having roast chicken, steaks & fries with salads, large glasses of beer. The carpaccio at a table nearby, when I finally figure out that that's what it is, is so covered with oil and garnishes that I'm glad I didn't go with that as I almost did. It's a steak place: go with the faux filet next time and you won't be dissappointed.

12:30. Time to go find my train. I hope it's not coming from Perrache, the other Lyon station, and just passing through here. I'd like to be able to get on early, out of the cold, and settle in for the 5 hours to Strasbourg. On the way I pick up some schedules for trains from Lyon. I have a discount pass to travel to this particular region that's good until May. I should take advantage. See some more of the little places.

Well, the train is coming from Perrache, so the crowd waits for it. I tried to reserve a window seat online, but was given an aisle, often a sign that the train is full. But no. They just decided to fill the reservations back to front. There are seven reserved seats in the entire car, which seats more than 50. All elbow to elbow at the back. So once again I pick the cleanest, unobstructed window I can find.

It's a pleasant ride, through the countryside of eastern France. The vineyards of the Jura roll by on their low hillsides. A paddock of shaggy ponies. A huge castle in the distance. Going through towns we have a good view of backyards, strewn with the things of life, swimming pools with ice on their covers. I took this day on the train instead of flying mostly to have this time of relaxation, time to look out the window and think of random things, read a book, just be still for a while.