psique

Someone's been a busy busy bee...

2010-05-21T20:52:00.001+01:00

Yea yea yea, I said I was gonna blog more often again - didn't really happen up to now, I know... But it's not my fault - seriously! Life's been throwing lots of exciting stuff at me recently and I sometimes don't quite know how to deal with it. The latest thing is something I'd love to write about but I'm not sure if I should, given it's very experimental in nature... In a nutshell, I'm going to be involved in some whole exome sequencing soon (and who knows, maybe I'll even land a first-author-Nature-paper like Ng et al)? I don't really have a clue about how it works yet, but am hoping to 'get it' fairly quickly once I actually come in contact with the subject matter. In that sense.. - anyone know of a next gen sequencing course/workshop happening in Europe or the US anytime within the next 4 months?? Alternatively: Anyone willing to travel to London and tell me all about it during a nice meal (paid for by Cardiff University ;)?

Anyway, lots of stuff has been happening lately, collaborations and other fun things, also private travel galore. I've met so many awesome people lately.. and I guess that's a direct consequence of me not spending a lot of my free time glued to the screen anymore like I used to (ie not web2.0ing much). I don't want to be unfair, I've met a whole lot of lovely people online too (like You , and You.. and You) but there's nothing better than a real-life hug or even just a real-life smile. Would you agree? I hope you do.

Scientifically proven...

2010-04-24T09:19:00.002+01:00

... to help reduce bacteria that cause bad breath.

So it says on the pack of gum I bought last night. Am I right in thinking they got it all wrong?

Science - almost by definition - is not about proving anything. It's about prediction, approximation, suggestion, speculation.. Sure, sometimes we discover a causative link between things - but you'd still be hard-pressed to find the word 'proof ' in a (life-)scientist's vocabulary.

Maybe that's a common misconception among non-scientists - that we are trying to prove things. We're not. The aim may be to discover the true nature of something, be it an organism, a mechanism or a particle, but we don't claim to know the truth. Instead we speak in p values, varying degrees of certainty that something works the way we suggest it to do.

There's a line in a recent song called Miracles (well worth checking out, it's fantastic..) by the Insane Clown Posse that says, "And I don't wanna hear from no scientists, all you motherfuckers are lying and getting me pissed". No, I'm not actually taking the song seriously but maybe this kind of attitude stems from the above-mentioned misconception? Because, really, how can someone lie if they're not actually claiming to be telling the truth, only an approximation thereof?

Someone's been a bad bad blogger..

2010-04-15T23:31:00.001+01:00

Anyway, not to dwell on it too much.. I just wanted to give a little update:

a) I'm revamping the look and feel of this space

b) I plan to blog more often (given that the last entry dates back to November, make of 'more often' what you will..)

It's not a lack of interest in writing that has prevented me from doing so, rather a lack of time combined with the firm assumption that the things that go through my head these days (and hence the things I wish to write about) are of no significant interest to anyone else. By 'things that go through my head' I mean the epic journey that will one day hopefully culminate in getting to write 3 letters behind my name / PhD / - which, so I've been told, are required for opening the Sesame of academic success.

In the near future I am hoping to combine both my love of the interwebs and my current mostimportantthinginlife by writing here more frequently, about the nature of my studies (genetics of young-onset Parkinson's disease) and anything potentially remotely associated with my academic future.

Hopefully my PhD-related out-takes will be of interest and/or use to others. If you just happen to be interested in other people's lives, however, there may be the odd nugget of wisdom from a troubled 26 year old progressive female to be found here, also..

In any case - stay tuned! (i.e. subscribe to my RSS feed, if you haven't already done so).

Cheers

PS: The actual appearance of this blog may be a complete mess in the next couple of weeks (months?) while I try out new things. If you've already subscribed to me via Google Reader or the like, please don't visit my actual site until I've reported major style/content updates - it would save a helluva lot of time (in your case) and embarrassment (in mine).

"I've done my damndest to rip a reader's nerves to rags, I don't want him satisfied."

2009-11-07T11:39:00.003Z

... and Steinbeck did an excellent job. 'The Grapes of Wrath' is epic, as you flip through the pages you become more and more engrossed with the migrant workers' lives, their suffering and their courage and strength. The noble Joad family and the people they meet along the way. You see the damage that industrialisation brought with it, but it's not the machines' fault, for machines were invented by people. Not to say that it shouldn't have happened, or that it was wrong, but it's important to be reminded of the sacrifices some people had to make when the industrialised capitalist machine started churning its wheels. Then the intercalary chapters, Steinbeck's staccato-esque writing style that naturally quickens your pace, sentence after sentence of simple despair and strong emotions, hunger and hope, hope and anger, the will to survive. I just finished the book last night and for a moment there I was inclined to start reading it all over again. Here's Chapter 21, one of the strongest chapters imho:

"The moving, questing people were migrants now. Those families which had lived on a little piece of land, who had lived and died on forty acres, had eaten or starved on the produce of forty acres, had now the whole West to rove in. And they scampered about, looking for work; and the highways were streams of people, and the ditch banks were lines of people. Behind them more were coming. The great highways streamed with moving people. There in the Middle- and Southwest had lived a simple agrarian folk who had not changed with industry, who had not formed with machines or known the power and danger of machines in private hands. They had not grown up in the paradoxes of industry. Their senses were still sharp to the ridiculousness of the industrial life.

And then suddenly the machines pushed them out and they swarmed on the highways. The movement changed them; the highways, the camps along the road, the fear of hunger and the hunger itself, changed them. The children without dinner changed them, the endless moving changed them. They were migrants. And the hostility changed them, welded them, united them hostility that made the little towns group and arm as though to repel an invader, squads with pick handles, clerks and storekeepers with shotguns, guarding the world against their own people. In the West there was panic when the migrants multiplied on the highways. Men of property were terrified for their property. Men who had never been hungry saw the eyes of the hungry. Men who had never wanted anything very much saw the flare of want in the eyes of the migrants. And the men of the towns and of the soft suburban country gathered to defend themselves; and they reassured themselves that they were good and the invaders bad, as a man must do before he fights. They said, These goddamned Okies are dirty and ignorant. They're degenerate, sexual maniacs. These goddamned Okies are thieves. They'll steal anything. They've got no sense of property rights.

And the latter was true, for how can a man without property know the ache of ownership? And the defending people said, They bring disease, they're filthy. We can't have them in the schools. They're strangers. How'd you like to have your sister go out with one of 'em?

The local people whipped themselves into a mold of cruelty. Then they formed units, squads, and armed them armed them with clubs, with gas, with guns. We own the country. We can't let these Okies get out of hand. And the men who were armed did not own the land, but they thought they did. And the clerks who drilled at night owned nothing, and the little storekeepers possessed only a drawerful of debts. But even a debt is something, even a job is something. The clerk thought, I get fifteen dollars a week. S'pose a goddamn Okie would work for twelve? And the little storekeeper thought, How could I compete, with a debtless man?

And the migrants streamed in on the highways and their hunger was in their eyes, and their need was in their eyes. They had no argument, no system, nothing but their numbers and their needs. When there was work for a man, ten men fought for it fought with a low wage. If that fella'll work for thirty cents, I'll work for twenty-five.

If he'll take twenty-five, I'll do it for twenty.

No, me, I'm hungry. I'll work for fifteen. I'll work for food. The kids. You ought to see them. Little boils, like, comin' out, an' they can't run aroun'. Give 'em some windfall fruit, an' they bloated up. Me. I'll work for a little piece of meat.

And this was good, for wages went down and prices stayed up. The great owners were glad and they sent out more handbills to bring more people in. And wages went down and prices stayed up. And pretty soon now we'll have serfs again.

And now the great owners and the companies invented a new method. A great owner bought a cannery. And when the peaches and the pears were ripe he cut the price of fruit below the cost of raising it. And as cannery owner he paid himself a low price for the fruit and kept the price of canned goods up and took his profit. And the little farmers who owned no canneries lost their farms, and they were taken by the great owners, the banks, and the companies who also owned the canneries. As time went on, there were fewer farms. The little farmers moved into town for a while and exhausted their credit, exhausted their friends, their relatives. And then they too went on the highways. And the roads were crowded with men ravenous for work, murderous for work.

And the companies, the banks worked at their own doom and they did not know it. The fields were fruitful, and starving men moved on the roads. The granaries were full and the children of the poor grew up rachitic, and the pustules of pellagra swelled on their sides. The great companies did not know that the line between hunger and anger is a thin line. And money that might have gone to wages went for gas, for guns, for agents and spies, for blacklists, for drilling. On the highways the people moved like ants and searched for work, for food. And the anger began to ferment."

the lights are on, but there's no one home

2009-11-04T00:15:00.002Z

standing in front of my house; waiting for the lights to go out.

source

Is human evolution over?

2009-10-20T20:27:00.002+01:00

The Large Chemistry lecture theatre in the main building of Cardiff University is packed with people - even the stairs are full. I luckily managed to acquire one of the last seats, and shortly beforehand one of the last glasses of red wine and a few peanuts, I might add.

On the screen a map of Utopia - as originally coined and pictured by Thomas More in 1516 - I suppose we're in for a pop science ride, but what else to expect in a lecture series called Darwin200? And after all, pop science can be really entertaining if it's done well.

While the speaker who's introducing Professor Steve Jones strikes me as a bit too nervous and generally mediocre (but then again that's usually the case), at least it becomes clear that Jones is not only a population geneticist extraordinaire, currently head of genetics at UCL (if you excuse the self-advertising), but also an established science writer and science communicator. Naturally, I feel sympathetic towards him right from the start, despite him looking rather blassé as the crowd starts clapping ferociously.

Instead of boring you with my account of the lecture, I suggest you take a look yourself. Chris coincidentaly found this video a few days back, of Jones giving the same lecture in Edinburgh, and while I haven't watched it, I suppose the content will be pretty much the same as today's lecture (maybe except for the regional Welsh jokes). I have to warn you though, while it's certainly an enjoyable lecture, I personally don't feel like he's answered his own question all too well. Jones is really a good speaker, but maybe he was trying to be too careful in his arguments, given that he was speaking to a lay audience..

Elect the Dead

2009-06-19T01:16:00.001+01:00

Don't you see their bodies burning?

Desolate and full of yearning
Dying of anticipation
Choking from intoxication

The first time I listened to Serj Tankien's debut solo album "Elect the Dead" I was taking a walk around my neighbourhood last December after a particularly vicious argument at home.

Why do we sit around and
break each other's hearts tonight?
Why do we dance around
the issues'till the morning light?
When we sit and talk
and tear each other's lives apart.
You were the one to tell me go...

I started out rather desperate, but within 5 minutes of listening to the album I began to run instead of walking in sadness, running rather fast for about 10 minutes (which, for me, was a big and unanticipated achievement - I'm anything but fit..) and feeling considerably more empowered afterwards.

Since then, Elect the Dead has been a staple on my mp3 player - every now and then there will be a moment when the music just fits. I'm not sure if the lyrics are political or deep or just pseudo-deep but it doesn't really matter. It's just great music.

She took my hand and I let her go
 She broke her little bones
 On the boulders below,
 Took my hand and she ended it all,
 Broke her little bones on the boulders below,
 And while she fell, I smiled.

If you're familiar with System of a Down, you should most certainly give it a listen. It might be a bit less rock-heavy, a bit less angry, less shouting and such than you'd normally expect - but the voice is at least as intense as on Toxicity. Elect the Dead is somewhat more melodic, and makes for excellent listening if you're oscillating between sadness and rage.

Do you know that life is ending,

As we go, the dots connecting,
We had our chance to save the garden,
As it dies, our souls will harden,
With these words chastising your conscience
Were breaking through and praying for
transcendence.

of wine and men

2009-06-09T17:20:00.004+01:00

"A few weeks after Thanksgiving I went out to dinner with an old drinking pal named Edward, a man in his forties I knew from back in the Elaine days. Edward is well known in book- and magazine-publishing circles and he's arrogant in the name-dropping sense, full of self-conscious bravado. He's also somewhat lecherous, the kind of guy who touches you a little too much, and stares at different body parts - your mouth, your breasts - when he talks to you. This didn't really bother me much in the past. Edward had been one of a series of casual friends I'd targeted as different from my family, representing a more brash and boisterous style, so I'd always liked hanging out with him, or thought I did. We'd go out to dinner a couple of times a year, and he'd always take me to fancy restaurants, and I'd sit and sip my expensive wine and listen to him tell stories and numb away any discomfort his ogling generated with my drink.
This time, with me sober, he took me to Biba, an elegant restaurant in the Back Bay, and he sat right next to me in a banquette, instead of across the table, and every time his leg brushed against me, every time he touched my hair or my arm, I had to resist the urge to take up my fork and plunge it straight into his hand. I didn't have the nerve to move, or to ask him to move, and I certainly didn't have the courage to plunge my fork into his hand, so I just sat there, ate my food, watched him drink his wine, and felt genuinely ill at ease for ninety-three full minutes. I clocked it: Here I am, forty-seven minutes of discomfort; here I am, fifty-three minutes; here I am, ninety-three minutes.
On his fourth glass of wine Edward looked at me and said, "You are an incredible woman." He was staring at my chest and I could smell the wine on his breath and for an instant I had a feeling of concentrated rage, as though every moment I'd ever sat in a restaurant feeling objectified and powerless and leered at had coalesced into that one minute (...) That evening left me with a creepy feeling, as though I'd stepped back into old clothes and found them rubbing against me all wrong. I got home and took a shower. I haven't seen Edward since."

- Caroline Knapp

Dark Nights of the Soul

2009-05-22T00:44:00.002+01:00

Loving this album recently brought out by Sparklehorse (aka Danger Mouse (yea, the Gnarls Barkley dude..)) called Dark Nights of the Soul. I'm currently listening to it for the fourth time in a row and I love love love it. I foresee it being killed by virtue of repeat, but so be it...

Apart from the music, I'd like to draw your attention to the fact that the album is being sold in shape of a 100 page booklet featuring photographs by David Lynch and a blank CD-R. Yep, that's right. The artists that have contributed to the album trust interested listeners to locate a suitable download (torrent) source themselves. Now, it appears to be more PR stunt than altruism or forward-thinking, as there's some copyright issues going on between Danger Mouse and EMI. But still, it's a cool move. I hope there'll be a lot of revenue for the booklet from 'real' fans or people - unlike moi - who can afford to blow 50$ as a sign of gratitude.

Anyway, I'm not a music critic, but lots of the songs are really good. And they really grow on you too (or maybe that's the wine..). Revenge featuring the Flaming Lips is fantastic; Little girl sung by Julius Casablancas, Angel's Harp, and Pain by Iggy Pop, to mention a few. Also (to stay in line with trying to copy a series of blog posts I would highly recommend, namely Lyric's Snippet) there's a song featuring Jason Lytle, whose lyrics may not be the most complex ever - but were the easiest to understand and are hence replicated below:

everytime i'm with you
i am drunk
and you are too
well, what the hell
else are we
supposed to do

yea, everytime you come by
we get so trashed
stay up all night
well, it's all wrong
but it's all right
yea, it's alright

and everytime i'm with you
i'm fucked up
and you are too
well, what the hell
else are we
supposed to do

everytime everytime everytime everytime everytime everytime i'm with you
i guess it's true

"We've got the corners and edges of the puzzle, but that's about it..."

2009-05-20T22:59:00.003+01:00

Phew. Just got back from a mini-conference on PD organised by the Parkinson's disease society in London. gReader greeted me with 433 unread items (why do Nature and J Neurosci have to unleash their new issues on my RSS aggregator on the same day? Hrmm...) but for once, this lil'creature of the night might actually make an early exit instead of giving in to her information addiction.

The conference was alright, but not amazing. You know things can't be that grand if a lowly PhD student already knows 80% of what is being said.. Or maybe that's just PD for ya - always trying to fit in whatever new gene/protein comes around into the existing mesh of mitochondrial dysfunction/oxidative stress/dopamine metabolism/proteasome dysfunction/protein aggregation/intracellular calcium imbalance/glutathione depletion/apoptosis/autophagy/inflammation/etc pp instead of coming up with something new..

Still, it was good to hear some big cheeses of PD research speak for the first time, e.g. Anthony Schapira (actually more of a mitochondria-type of guy), Maria Spillantini (alpha-synuclein, baby!) or Nick Wood (who turned out to be my supervisor's supervisor as we shook hands - how inbred ;). It was also good to see my MSc supervisor Rina again (from what I gathered my DJ-1 project did indeed turn out to be a bit of a dead end road, so maybe it wasn't just my poor pipetting skills...). I suppose five hours of PD recap never hurt nobody. From what I heard, Eric Ahlskog's talk was really good, but I missed that one thanks to drug-seeking behaviour.

What I didn't like too much was a moment towards the end of the conference when the chair (who represented the PD society I suppose, which explicitly wants to help find a cure) said: "Well, I think we've done a pretty good job with Levodopa". I just thought: Really? Are you serious? Sure, L-dopa is effective, but it's been around for half a century and comes with considerable side effects. We had a few people with PD in the audience, and one of them kept on jerking his head sideways, like a massive tic. Another had difficulty biting off of an apple because his head and hand just wouldn't coordinate. It was rather sad. Besides, L-dopa doesn't stop DAergic neurons from dying, but since it's not our own brains that are deteriorating it's easy for us scientists to say (and some did) that we should reach for the low-hanging fruit and work on better control of symptoms instead of trying to develop neuroprotective treatments.. Of course better symptomatic treatments are needed, but what about that promised cure? Oh right, I guess we'd have to know how PD actually really works first.. :P

Anyway, I tried to do my part (for the day) and read a bunch of PhD (albeit not PD) related papers during the trip, including:

Kraft & Hunter (2009) Genetic Risk Prediction - Are we there yet? NEJM 360: 1701 - 3. (allrightish commentary on the 'real' risks conferred by the genetic variants we've uncovered up to now and what's to come)

Abbott (2008) The Brains of the Family. Nature 454: 154 - 7. (very interesting topic: psychiatric genetics; but a news feature and hence quite simplistic)

Moore (2009) From genotypes to genometypes: putting the genome back in genome-wide association studies. EJHM. (short and sweet and about epistasis - just how I like it ;) gonna have to read Emily et al and Pattin et al sometime soon)

Goldstein (2009) Common Genetic Variation and Human Traits. NEJM 360: 1696 - 8. (pessimistic as ever, but maybe rare variants are the silver lining?)

Hardy & Singleton (2009) Genomewide Association Studies and Human Disease. NEJM 360: 1759 - 68. (good, comprehensive overview of what GWAS can and cannot do)

Coming back earlier was weird, maybe it was the residual blood alcohol concentration from the reception at the end of the conference or the fact that I usually don't leave my house at the crack of dawn, but in any case it felt as if I had been away for days, not just 16 hours. An almost dream-like feeling. Speaking of which... I'm off.

Free brain scans for All!

2009-05-19T23:15:00.000+01:00

Earlier today I was attending a talk by Nick Fox from the Institute of Neurology (UCL) on dementia and imaging techniques. I've calmed down now, but at first his talk got me quite upset.
For one, watching those videos of some of his patients were quite sad. You'd get the tragically funny disinhibited lady with frontotemporal dementia; the man who couldn't remember such mundane words as rose bush or thorn, and would continue losing most of his vocabulary thanks to his left temporal lobe resembling a crumpet (half eaten); another man who couldn't whistle, blow out a candle or cough on command anymore - not because there was something wrong with his mouth, but because he just didn't remember how to.

The patient who had the biggest impact on me, however, was a woman, maybe in her late fourties, who was complaining of small glitches in everyday memory. She was subject of Fox' attention because early-onset dementia ran heavily in her family (I've forgotten if they had identified the gene(s) responsible). This woman still seemed pretty normal, and one could forgive her for exaggerating her troubles with memory given her family history. However, she was a prime example for what Fox called 'registration' - the process of performing yearly MRI scans and letting a computer program figure out volumetric changes in brain matter. And sure enough, over the course of about 7 years one could easily see how her hippocampi shriveled up and her ventricles ballooned. First - albeit very mild - symptoms became noticable to her husband about 2-3 years into that process. Someone asked if the woman herself had gained insight into her disorder and loss of memory. "Yes, she did. And then she lost it again." was the answer and at this point I could feel my eyes getting wet. Needless to say said patient is long gone.

You see, Fox is a great speaker and he gets his point across. The point being that various imaging techniques (not just MRI, but also PET and fMRI) could and should be used to facilitate diagnosis, measurement of disease progression and maybe even enable detection of pre-symptomatic changes.

There's Alzheimer's disease, vascular dementia, dementia with Lewy bodies (which I've touched on before), frontotemporal dementia and others, but often enough the real diagnosis is not confirmed until after death and patients get labelled as merely demented. I can imagine that it takes a specialised neurologist to distinguish the symptoms properly, and as long as good reliable biomarkers are lacking, imaging could help to figure out which kind of dementia is eating away at the patient's brain. After all, the 'topography of loss' depends at least partially on the disease at hand, even if we don't fully understand yet why we see selective hippocampal loss and cortical thinning in Alzheimer's, while frontotemporal dementia does what it says on the tin (although it comes in different flavours), and DLB can affect the basal ganglia to varying degrees. (Actually, it would be probably be pretty insightful in terms of molecular mechanisms if we knew what causes certain areas to be selectively affected, what exactly makes some neuronal populations more vulnerable than others, but for that as well, we have to catalogue which areas are hit first in a given disease etc).

And apart from making for good material for sad videos, tracking progression of brain atrophy could also be quite informative. I wouldn't be surprised if familial dementias would be accompanied by accelerated deterioration or maybe different patterns of progression or something similar. Or - in a better world - imaging could allow clinicians to see if a given medication is halting neurodegeneration on the gross structural and not just symptomatic level..

Early detection, though, is what stuck with me the most. In Parkinson's disease, up to 90% of neurons in the substantia nigra are lost before the onset of symptoms. Ninety Percent!!! While this suggests on one hand that the brain is surprisingly plastic and can make do with a substantial amount of damage, it also means that the factors responsible for cell death start quietly wrecking havoc years and years before anyone could notice. I don't know about you, but I find the idea that my parents' brains could be quietly turning to mush right this instant without anyone knowing about it quite distressing. My first reaction was: Why can't we all have MRI scans for all (or PET scans for that matter, which can predict whether people with mild cognitive impairment will progress to Alzheimer's disease based on amyloid binding)? Every 5 years from 30 onwards, and every two years once you turn 50? Is that too much to ask? I guess it is. In most countries even basic healthcare is a luxury, and even those fortunate enough to live in countries like the UK or the USA probably will have to wait quite a bit till they start getting invitations for brains scans the way women are recruited for pap smears these days. All the things Fox talked about didn't seem to be exactly breaking news, yet implementation of routine brain scanning beyond research and severe/suspicious (eg familial) cases seems to be anything but widespread (He did mention that it's more common in the US than in the UK, though). I have no idea how much various imaging techniques cost. I just really hope the cost will come down and the quality will continue to go up. It would be nice to get a prediction of some sort, like - in 20 years time everyone will undergo routine MRI scans - or at least my children will, or at least everyone with basic health care insurance will, or whatever..

Now obviously early detection alone isn't gonna do much. "Uh, sorry Sir, but your hippocampal volume is decreasing at a steady rate of 4% per year". That's not very helpful (apart from it making for a good excuse for why you keep on forgetting that you wife asked you to take out the trash). No, what we ultimately need are new treatments that can effectively prevent or at least slow down brain atrophy. With the stuff that's out there at the moment, L-dopa for Parkinson's, NMDA antagonists or acetylcholinergics for Alzheimer's, we're just retrospectively trying to make up for the lost cells and their original function. How crude. How much better would it be if we could develop neuroprotective drugs and stop these cells from dying in the first place? I know that's exactly what scientists all over the world are trying to do. I just get really impatient sometimes...

PS: Incidentally I couldn't remember for the life of me why Fox' talk seemed so familiar until I googled him and consequently my harddrive - and voilá: it turns out he gave a lecture during my Masters back at UCL. Hrmm. (Just kidding, I know I'm not demented - yet.)

PPS: Probably gonna spice this post up with references and links sometime within the next few days, so if you made it this far, check back again. For now I'm off to bed, got a whole day of mingling with PD researchers in London ahead of me (which by virtue of me living in the Diff means catching a train at stupid o'clock).

Did you wanna say something or is that just your parietal cortex?

2009-05-17T23:15:00.004+01:00

Shamelessly stolen from Science's "This week in Science" summaries, dating back to the 8th of this month.. Why? Because we are shown yet again that 'we' are our brains, not some elusive spiritual substance with deep meaning. All it takes is a couple of electrodes and the right stimulation parameters.. Well, personally, I think that's fine.

"Where in the brain are our intentions formed and how do we becomeaware of these intentions? Desmurget et al. (also see thePerspective by Haggard) investigated the effect of direct corticalstimulation of parietal and premotor regions in patients undergoingbrain surgery for tumor removal. Stimulation of the parietallobe provoked the conscious experience of wanting to move theupper limb, lips, or tongue without any concomitant motor activity.When stimulation intensity was increased, patients believedthat they had actually moved or talked, but again no muscleactivity was detected. When, however, the premotor region ofthe frontal lobes was stimulated, real complex multijoint movementswere induced. However, patients did not experience these movementsas produced by a conscious internal act of will. Indeed, theywere not even aware that they had moved. Increasing stimulationintensity increased the amplitude or complexity of the movementbut never made it reach consciousness."

Refs:
Desmurget, Reilly, Richard, Szathmari, Mottolese, Sirigu (2009) Movement Intention after Parietal Cortex Stimulation in Humans. Science 324: 811 - 3.

Haggard (2009) The Sources of Human Volition. Science 324: 731 -3.

What do you want to do today? (rant)

2009-05-16T16:10:00.001+01:00

The plan for today was to go to the lab at some point, and try to finish off my sequencing. But now it's already 3pm and I really truly can't be asked. The trouble is that I've been meaning to finish this particular project for the past few weeks, it just happens to be a) a fairly uninspiring endeavaour (screening YOPD patients for mutations in PINK1 is not exactly the kind of research that will result in surprising findings, a C/N/S paper or academic recognition) and b) a major pain in the ass because the PCR gods weren't with me in the beginning and I had to do tons of repeats (sometime I start to worry whether I'm just no good at the bench..). Add to that the growing frustration over some organisational issues in our lab as well as my multichannel pipette's inability to suck up 3 microliters into each of the eight tips, not just 5 of them, and an overall sense of inefficiency and you get a rather unhappy lil'scientist.. Once I'll actually be done with the sequencing things should get better again. Checking the variations I've found against dbSNP or writing up the whole thing shouldn't be too bad, but as to the wet lab side of things, I've really had enough for now. Can't wait to get back to playing with PLINK or find some other ways to use our GWAS data. Right, end of rant. As I said, I've been meaning to go to the lab and finish the sequencing this weekend, but all work and no play makes Jack a dull boy indeed..

So, screw the lab; I'm staying home. Today AND tomorrow. I'm certainly not at a lack of things to do either, the trouble is just that the guilt over not doing 'real' work could result in entering a mindless web 2.0 loop or going back to bed in the middle of the day.. It's happened many times before and it's not pretty. In order to prevent this from happening, I should continue listening to upbeat (or at least not depressing) music, keep the coffee coming, and make a list of possible activities for whatever's left of the weekend. This will be boring, so you might wanna direct your cursor to some other link right about now...

book flights for my upcoming trip home and to Choroni in Venezuela.
compress the number of unread gReader items to <200.
compress the number of unread ScienceDirect alerts to <400.
transform my pigsty back into a flat.
go for a walk with some Nature Medicine or In Our Time podcasts.
write a number of long overdue proper emails/messages.
finally read those perspectives on GWAS that appeared in NEJM a few weeks back.
turn one of my recent blogging ideas into a post of actual value (as opposed to this).
start looking for a place to live next autumn.
dye my hair.
look into ALOHOMORA (the linkage analysis tool, not the Harry Potter spell).
update my RSS subscriptions from neuro/psychology-focused blogs to more relevant bioinformatics and genetics blogs.
go to Milgi with a friend for some quiet drinks and a much needed update.
phone the family.
buy or make a wall calendar in A1.
distill the top 30 or so papers I should read out of the list of 100 must-read publications for grad students.
write an outline for my upcoming lab talk (aka the horror).
work out the details of a little dialogue that came to mind recently for my short story.
go see the Serious Brain Power and/or Diane Arbus exhibitions at the National Museum in town.
....?

for larger circumference, add friendfeed

2009-05-16T13:32:00.005+01:00

by Erin Hanson, at The Daily What, via Pierre.

Human Ageing Genomics Resources

2009-05-12T01:35:00.001+01:00

As I was reading a paper earlier about chromosomal region 11.5p and its putative association with aging (Lescai et al, 2009) I came across an interesting sounding url, namely http://genomics.senescence.info. Turns out that the website is home to HAGR, an interdisciplinary project devoted to the genetic study of aging developed by Olivier Touissant, George Church and João Pedro de Magalhães (and probably kept up by lots and lots of sleep-deprived post-docs ;). Their mission statement can be found here, and I shall attempt to provide a brief description of HAGR in the following paragraphs.

GenAge constitutes a major part of the site, and is a manually curated database of genes which could possibly be associated with human aging, largely based on studies done on the usual suspects: Mr. Mouse, Drosophila, C. elegans, and yeast. A query results in the usual info being displayed, such as sequence, gene expression, putative function of the protein product etc. The database holds 261 genes, as of last summer.

The AnAge database on the other hand contains entries for over 4000 animals and some basic life-span-related facts. For example, the maximum life span for lions is 27 years, while atlantic salmon reaches sexual maturity after ~1800 days, and the snowshoe rabbit has a basal metabolic rate of 67080 W. The point of this collection is to understand why different species age at different paces, and the authors have started by comparing the mitochondrial genomes of different species. In addition, the group also seems to have taken a liking to the naked mole-rat, which has a project of its very own.

And then there's the 'Δ Project', the aim of which is to figure out transcriptional differences between young and old organisms. Turns out that the group's efforts to mine 'expression data to identify robust patterns of age-dependent regulation' were described last month at Ouroboros, based on a recent publication by de Magalhães et al. And there I was wondering all evening why the name sounded so familiar... (D'oh).

Anyway, in addition to the information available at HAGR, you can download their databases from the site and under the Software header you can find an SPSS script and a Perl toolkit for playing around with genomic and demographic data (Note to self: must get to grips with Perl). And if all that wasn't enough, there's a long list of other databases and bioinformatics resources centered around gerontology and genomics. I shall try looking into several of those in the near future (and probably go insane in the process).

I have to say I'm a bit sceptical when it comes to how _human_ genetics can inform us about aging (model organisms are a different story, one which I know nothing about). Sure, you get the obvious: genetic contributions to aging-related diseases eg Alzheimer's, late-onset Parkinson's, other dementias, diabetes, cancer, cardiovascular diseases etc, which might then inform us indirectly about environmental contributions, molecular pathways or general aging. Apart from that, I'd like to think that the study of epistatic gene interactions could be very informative, but that field is really only just emerging and better coverage of the genome is needed (which hopefully won't be much of an issue anymore, say, 5 years down the line..). I think it's very unlikely that we'll find single genes which substantially affect the aging process the way they do in species such as C. elegans or yeast (and the paper I mentioned in the beginning seems to support that notion). But I suppose in the coming years our ability to pick up on genes and genetic variation with small effect sizes and lots of interactions will improve substantially. Let's hope so anyway... *wanders off pseudo-philosophising*

----
Reference: de Magalhaes, J. P., Budovsky, A., Lehmann, G., Costa, J., Li, Y., Fraifeld, V., Church, G. M. (2009) "The Human Ageing Genomic Resources: online databases and tools for biogerontologists." Aging Cell 8(1):65-72.

...other relevant publications.

What is rewarding brain stimulation?

2009-05-11T20:34:00.007+01:00

We've probably all heard of deep brain stimulation being used to treat Parkinson's disease and related movement disorders such as dystonia by now. Also recently, clinical trials investigating DBS as an option for treatment-resistant depression as well as obsessive compulsive disorder have gained approval by the FDA.
What might be a bit less well known, despite having been around since the 1950s, is the concept of rewarding brain stimulation. When you really want something, or feel really driven and motivated, it's because certain dopaminergic brain areas are being activated. RBS can induce this feeling artificially and successfully reinforce whatever behaviour is tied to the stimulus. The following is a short (2min) video describing the basics of RBS.

I think RBS is a neat demonstration of just how easily brains and behaviours can be manipulated.. Anyway, for more brainy videos check out the iPlant channel or visit the iPlant site for an extensive collection of references, and ideas on the potential uses of RBS in humans.

of art and science and beyond

2009-04-26T22:45:00.003+01:00

Yesterday I made a little excursion beyond the familiar world of science. A friend of mine, who is finishing her BA degree this summer, was talking me through her third year art project. It was quite fascinating to say the least, so I figured I'd try to share.

Her final piece is not complete yet, in fact it currently only exists as a more-or-less fleshed out idea in her head and in various bits and pieces. Once it all goes live in an exhibition in about five weeks time I might add pictures to this post but until now my meager descriptions will have to do.

What she showed me were samples, little pieces of work she had produced in order to figure out what she wanted to convey with her art, how she could convey it, and what shape the final piece could take. I was never aware of just how much thought goes into the process of creating a work of art, I always kind of assumed that (contemporary/modern) artists worked on the fly, that their ideas just came to them like strokes of insight. Hence, I could never really appreciate modern art ("A red square on a white canvas? Really??") Well, apparently, that's not true at all (well, maybe it still is for some people). The way she described the process reminded me of research and scientific experiments time and again, and it was quite humbling, but maybe it will make more sense if I just try to recapitulate what she did..

Her early pieces were little balls made of paper pulp and human or horse hair (more about those later on). Other early works were stitches made of hair and threads, but as she correctly pointed out, these looked too orderly, like the little table cloths your grandma would put under vases. She then made these stitches a bit messier, with holes in them, looking more like spider webs (made by spiders on acid, mind you), but somehow that direction didn't quite work either. Her latest pieces, which are most likely to be included in her final project, were said stitches of hair and thread, but shaped into pebbles. In fact, she had made them by wrapping her material around pebbles she'd found on the beach, and the hairy concoctions somehow retained that shape after the pebbles were removed. Another piece looked like a snake skin, made of paper pulp, but while it made sense in light of what she wanted to convey, I'm personally not sure how it fit in with the other pieces. It will be interesting to see how she makes the pieces fit together in the end.

She wanted to evoke some emotion with her work, she wanted it to be personal without giving too much away. Topics she explored over the course of her preparations were change, loss, mourning, as well as Freud's concept of heimlich and unheimlich, i.e. the secretive (or family secret, as heim can also mean home) and the uncanny.

One of the hairy paper-balls in particular, instantly reminded me of teratomas (not that I've ever seen one, but this is what I would imagine some of them to look like). It looked like a clump of skin and hair, like the things you hear about sometimes, where a disformed incomplete fetus or parts of it are found in the body of a healthy fetus. Maybe that image (graphic!) wouldn't have come to mind if I hadn't read about something similar a few days back but still. Let me tell you, it was quite uncanny. I told her about the concept of the uncanny valley, which also came to mind when we talked about Freud's concept.

We also talked at length about hair and how us humans think it's fine as long as it's attached to our bodies but get grossed out as soon as it's lying on the floor, sticking to our clothes or swimming in our soup. To think that some people sleep on mattresses filled with horse hair - gross! At home we used to joke that we could make a whole range of jumpers out of our dog's black thick hair, but who would actually wear those things? (Then again, sheep hair seems to be a-okay). In any case, there was no logical explanation for the uncannyness, and her idea to use hair in her work suddenly made much more sense in light of these thoughts. Before it had just seemed a bit like an artistic quirk that a 'scientist' like me would sneer at.

As mentioned earlier, I was quite amazed at the amount of thought and work that had gone into her art.. Other preparations included sketches, going back to artists who had done similar things, and lots of photos of her work, with the beach as a backdrop. She had also considered suspending her work but deemed that too difficult to do, and she was obviously stressing out about only having 5 weeks left. "If I had only started earlier..." Well, procrastinators of the world - don't we all know how that feels? She was also playing with the thought of including feathers in her work (and we discovered that some people have a serious ostrich fetish). I tried to express whatever came to mind when I saw her work, as a sort of feedback from a layperson. But obviously her tutors might view the subject matter very differently, given that they've been into the whole creating-art-process for many many years. For example, it wasn't enough to just have a good idea behind the art, it would also have to be perfectly executed; maybe not unlike a western blot, which might only prove a minor point but would have to be immaculate to be accepted for publication (unlike the shit I produced for my master's thesis).

This brings me back to the parallels I saw between art and science. There's a long process preceeding results in both domains, yet we usually don't get to see that process. In the scientific literature you get neatly written publications: Abstract. Introduction. Results. Discussion. References. Maybe some supplementary material if you're lucky (but who bothers looking at that?) You get a clear hypothesis postulated by the authors, followed by proof that said hypothesis is correct. (Unless you're reading the journal of negative results in biomedicine, that is). All the painstaking trial-and-error that goes into the work is usually not evident at all (and this can seem quite daunting for a young researcher who doesn't yet know how the system works, because you end up wondering why *you* can't come up with neat hypotheses and well-designed experiments on the go but actually make mistakes and have to refine your thoughts all the time..).

In any case, the experience really made me re-think my perception of art and forced me to step off my slightly elitist scientific high chair for a bit (a prelude to this might have taken place a few weeks earlier actually, when I was very briefly introduced to computer science and the - for me very puzzling - issue of encrypting stuff on the web). I used to mourn the lack of like-minded friends who were also in the biological sciences, but now I'm thinking it would actually be better to move around amongst a circle of friends who do all sorts of different things, with the only prerequisite being that they are passionate about what they do, because that way I could learn much more about all the cool things that are happening in this world thanks to our disproportionally large brains, instead of eternally residing in the ivory tower and looking down on everyone who's not into the subjects I happen to entertain an interest in..

Hourglass IX

2009-04-14T21:53:00.000+01:00

Welcome to the ninth edition of Hourglass, a blog carnival devoted to the biology of aging!

I want to begin with the first picture-post submission to Hourglass by Mo Costandi, which you can see (and click through to) on the left. Gama sennin, a figure from japanese mythology, "is said to live forever, able to change himself into a toad. He is one of the immortal sages (...) who are associated with longevity and medicine. He is also the creator and manufacturer of magical pills, and whomsoever manages to secure them is able to extend his lifetime."

~Hara Hachi Bu~

Speaking of Japanese culture, "Hara hachi bu" is how the Okinawa, reknown for their long life-span, call the practice of eating only until you are 80% full. And well, what do you know, one of the few methods which reliably extend healthy life span (at least in model organisms) is calorie restriction. While I'm not sure whether it is really that much easier to eat nothing for 2 days per week as opposed to chronically reducing one's intake by about 30%, Lloyd and Peggy Morris tell us how that particular regime has been working out for them in Out and About. Meanwhile Reason is a bit pissed off at how calorie restriction has recently been portrayed in popular media, namely at Oprah's show, and rightfully so. To quote: "A theory on popular media: the more popular it is, the less the information it provides bears any semblance to accuracy, truth, or scientific fact".

~I have full faith in the future of medicine~

This is the tongue-in-cheek reply people who comment on my smoking usually get. While I’m aware that it’s probably not quite what the authors of the next two posts had in mind, this attitude may just be the next best thing to quitting (albeit by a long margin.. ;).

For one, optimists live longer, and are specifically less likely to die from heart disease, who would have guessed? The reasons for this are unknown, but Ward Plunet at Brain Health Hacks points to a number of possible explanations. For example, optimists are more likely to stick to medical advice and may also benefit from a bigger social circle as compared to their grumpy pessimistic counterparts.

And in another post at Fight Aging!, Reason urges us to abandon our evolutionarily conserved short-sightedness and truly think forward. This is a very valid point imho. While one shouldn’t underscore the impact of a healthy lifestyle on life expectancy, it is just as important to keep in mind that the real changes in terms of extending healthy life span will be due to new advances in technology and medicine, and we need to actively push the appropriate areas of research instead of relying on carrot juice alone.

So how about trying to optimistically and proactively look into the future? As a starting point one might want to take a look back for inspiration, at what has been achieved in aging research to date. Paul House has created a Science of Aging timeline, and encourages people to add referenced entries to it. It still looks like early days, but I am pretty sure this could become a great interactive tool for exploring aging research as soon as some more people contribute to it. So if you can think of a cool milestone in biogerontology, please add it to the timeline.

~Experiences after reproduction don't influence the evolutionary process~

as Martin Wiseman (a big shot in cancer research) said in a lecture I recently attended (the lecture was useless btw). This is a bit of a bummer, as it means that characteristics that would extend life span are not necessarily evolutionarily selected for. This might be the case regarding amyloidosis, a clogging of blood vessels and other body tissues over time with various proteins, which Reason speculates might be the ultimate killer if heart disease, cancer or being eaten by bears 'fail' to do the trick. Our bodies might simply not have had the need to get rid of those protein deposits until quite recently. At Fight Aging!, recent advances in our understanding amyloidosis and CPHPC, a promising drug which clears amyloid deposits by preventing them from being protected by a protein called SAP, are described.

Abnormal protein deposits also pose a real problem in several neurodegenerative diseases by the way, for example in Parkinson's disease (hello alpha-synuclein, I'm looking at you!) or Alzheimer's disease. Another example is Huntington's disease, in which abnormal mutated huntingtin accumulates in brain cells. Recently researchers found that acetylation of huntingtin might impact positively on its clearance, and without a doubt learning how to "convince the body to clear its own biochemical waste" could be helpful in fighting a multitude of aging-related diseases (or even 'normal' protein accumulation associated with aging - see above).

~In effect, aging occurs because (...) genes evolved to treat the body as disposable~

as postulated by Thomas Kirkwood in his review: Understanding ageing from an evolutionary perspective (a great piece!) Alas, biogerontologists essentially have to try and fight our bodies' propensity to die once their use has been fulfilled. Funnily enough, even the 'blueprint of life' itself gets damaged over time.

Several types of DNA damage have been implicated with aging, and mitochondrial DNA seems to be no exception. In his post on mitochondrial DNA replication and premature aging at Ouroboros, Mark Walsh elaborates on a recent paper by Bailey et al (free full access :) who studied mutant mice that had a proofreading-deficient mitochondrial DNA polymerase (POLG). In these mice, linear mtDNA, and point-mutations were more common. Also, DNA replication appeared to stall at specific location in the mitochondrial genome, leading an upregulation of replication and possibly additional stresses on the cell as a whole. Interestingly, the human progeroid disorder Werner's syndrome is caused by mutations in the WRN helicase, which is involved in nuclear DNA replication and repair. If all this made little sense, I urge you to check out the original post, where it's all explained much more coherently.

Aging is also associated with a wide variety of changes in gene expression and a plethora of studies have tried to pinpoint those, up to now largely in vain, due to the vast inter- and intrapersonal variation in gene expression. Kristen Fortney at Ouroboros writes about a recent effort by Magalhães et al to mine 27 existing microarray studies in rodents and humans for gene expression changes associated with aging. A total of 73 genes were found to be differentially expressed in relation to aging, and as Kristen notes: "Genes emerge as significant here only if they demonstrate a strong age-associated profile across a range of very different conditions (...) The advantage is that those genes (...) are likely to be the really interesting ones – components of a common aging program that operates in multiple tissues."

Okay, so this is the end of Hourglass IX; I hope you enjoyed reading! Please make sure to check out previous editions, think about contributing or hosting even - more info can be found here.

I'm going to end with a quote I found on Paul's website, the best part of which is the date, imho:

~These bodies which now we wear belong to the lower animals; our minds have already outgrown them; already we look upon them with contempt. A time will come when Science will transform them by means which we cannot conjecture, and which, even if explained to us, we could not now understand, just as the savage cannot understand electricity, magnetism, steam. Disease will be extirpated; the causes of decay will be removed; immortality will be invented~. -Winwood Reade, 1872, from his book The Martyrdom of Man

storm

2009-04-14T18:43:00.001+01:00

Submissions wanted for Hourglass: Biogerontology Carnival extraordinaire

2009-04-08T10:39:00.003+01:00

Just a little primer... Next tuesday I'll be hosting the 9th edition of Hourglass, which is a blog carnival devoted to the biology of aging and biogerontology.

I really hope you'll contribute, almost anything aging-related goes, as "topics of posts should have something to do with the biology of aging, broadly speaking — including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. Opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. If in doubt, submit anyway."

You can submit your entry to [hourglass.host][at][gmail][dot][com]. We're also looking for someone to host the next editions of Hourglass, so if you're interested please contact Chris.

Previous editions and more info can be found here at Ouroboros.

cheers darlin', revisited

2009-04-08T00:50:00.002+01:00

you know things are bad when you're listening to damien rice, and your bottle is too empty and your ashtray is too full to properly put out your cigarette.

Self-determination for the 21st Century

2009-04-07T00:22:00.003+01:00

Yes, the iPlant is a dangerous idea - but it's also a very appealing one, don't you think? And wouldn't it be better if it was us (neuroscientists, computer scientists, engineers, philosophers..) working on it then, than say DARPA et al? The idea for the iPlant didn't arise in some shady military lab or behind closed doors - instead it is a great example of open-source science, a fact that unfortunately seems to get overlooked by the critics.

This is not a quest for power or world domination. It's a quest for a device that could potentially relieve at least some of the suffering associated with the human condition. Many people want to use their time and intellect for 'good' things or simply want to live 'good' healthy lives, yet they are held back by evolutionary conserved, but now obsolete behaviours and drives (like overeating, or 'lazyness' which is really just an attempt to save energy). We are aware of this, yet change is difficult and as a consequence we feel bad about being sloths and gluttons. Our 'higher' brain structures 'know' we won't die of starvation tomorrow if we don't gorge on pizza today, they 'know' that the long-term benefits of learning a new language exceed the short-term benefits of staying in bed or watching TV. But more often than not our 'lower' structures succeed in directing our actions. It's almost like our brains haven't quite gotten the hang of life in the 21st century yet (at least life in a economically and socially privileged position).

The iPlant could enable us to do what we want to do more often, and become who we want to be. It help us tweak Doya's equation in our favour. By giving us the ability to actively direct our motivation to certain goals it could therefore enable an artificial form of free will (in the popular sense of the word), or at least destruct the out-dated notion of us having any.

Look here Facebook, this is how it's done..

2009-04-06T17:17:00.011+01:00

FriendFeed rolled out its new beta version today, and what do you know - people actually actively engage in discussions about the new interface and features; talking about what they like and don't like, what they're missing and what could be improved. Maybe the developers behind FriendFeed will do what they think is right anyway, but i'm pretty sure they'll take into account at least some of the feedback, especially since they're explicitly asking for it.

And you know what's so great about this? Introducing a new version to anyone who's interested makes the users (or at least me) feel like the site is actually being improved for them. And it is done in such a way that feels quite democratic, as opposed to Facebook's: "We know what's best for you"-attitude and just rolling out new features and assuming that users will adapt. Yes, Facebook is massive and a lot of people will rather get to grips with some new design/feature they don't like instead of leaving the site because they've come to rely on Facebook for communicating with their friends and family. One could argue that FriendFeed is being considerate of its users input just because it can't yet afford not to be, but it seems to me that the democratic approach is rather due to an inherently different philosophy (which also manifests itself in the fundamental difference that FriendFeed allows for greasemonkey or other scripts that change appearance/functionality. But that's a story for another day - and someone who actually knows something about it...).

Now I don't know how much technical trouble having a beta site run alongside a fully developed old version entails, but if I remember correctly Facebook had a sort of beta version available for weeks before implementing the new interface during its last large update a year back or so. So it's not like it can't be done or like the whole beta concept is unbeknownst to Facebook..

In any case, it makes FriendFeed seem a whole lot friendlier than Facebook. Instead of dumping a new version onto its users and only changing things in retrospect after lots of complaints, Friendfeed actually seems to 'care' what its users think. And i think that's a very good approach.

So, regardless of whether the new changes are actually any good (which I think they will be once refined), or each site's purpose or scope.. - Friendfeed 1: Facebook 0.

disorders with synuclein pathology and parkinsonism

2009-03-26T18:26:00.003Z

neurodegenerative bits and bobs

2009-03-03T23:59:00.000Z

--incredibly lazy repost--

Parkinson's:

Bick et al (2008): Specific cytokines change protein expression and localisation patterns of alpha-synuclein, ubiquitin and tau in primary glial cells.

Azmitia & Nixon (2008): Serotonergic axons degenerate in PD forebrain.

Costa et al (2008): D2-block and carbamazepine protect striatal neurons from rotenone toxicity (mitochondrial complex I inhibitor) via a GABA-mediated mechanism.

Wisman et al (2008): Messing with convergent dopaminergic and cholinergic neurotransmission relevant to hippocampal working memory might be responsible for cognitive dysfunction observed in PD.

Blanchet et al (2008): Resveratrol attenuates MPTP-induced depletion of striatal dopamine.

Alzheimer's:

A decrease in connectivity of the hippocampus and posterior cingulate cortex is found in patients suffering from Alzheimer's disease (AD) and mild cognitive impairment (MCI), and visualising these abnormal fiber connections could facilitate early detection of AD. Zhou et al (2008) Alzheimer's & Dementia.

Profiling of neuronal changes in gene expression could provide a mechanism of identifying people with pre-clinical AD, as seen through analysis of gene expression in non-demented individuals with intermediate AD neuropathology. Liang et al (2008) Neurobiol Aging.

Two different transgenic mouse strains (C57BL/6J & DBA2/J) display different levels in beta-amyloid, despite amyloid precursor protein (APP) levels being the same. This could be due to genetic variations in three different loci, which have also been implicated with AD in humans. Ryman et al (2008) Neurobiol Aging.

Administration of grape-seed derived polyphenolics to Tg2576 mice (a model of AD) decreased levels of soluble oligomeric amyloid-beta and attenuated cognitive deterioration. Wang et al (2008) J Neurosci.

some friendly advice..

2009-03-03T22:33:00.000Z

dear anonymous surfer from kalamazoo, michigan,

if you were searching for "free adult ass" and somehow ended up on this blog, may i suggest trying a different search engine? how about this one, for example?

my thoughts exactly

2009-02-25T23:22:00.002Z

an incredibly deep post about parenting, gender and cereal..

2009-02-20T11:24:00.008Z

Dear Cereal People at Nestlé Germany,

Yesterday I came across a box of your cereal. I'm one of those people who read cereal boxes you see (then again, who doesn't?), and what I saw on this particular box while munching on a handful of your most exquisite CiniMinis almost made me spit them out again. So what was it? A little box with nutrition*-related information, entitled: "Advice for Mothers" (translated, the box is actually in German). "Advice"? Nothing wrong with that. But "for Mothers"?? I mean, really?? Maybe your cereal-box designers live in a cave behind the moon or something, but I would have thought that in the 21st century it's not just mothers who feed their children cereal anymore. I guess writing "Advice for Parents" would have been too egalitarian and would have triggered an outrage among all the house wives and mothers you are trying to reach out to...

Is it just too difficult for you to imagine that there may actually be fathers out there who purchase and administer cereal? But maybe you don't want to take the opinion of an annoyed young female who is in despair and disagreement with the role she is supposed to play in society one day into account. That's fine. We can look at this issue from another perspective:

Consider a young emancipated dad who's trying to find some food in the hunting grounds that are supermarkets.. or who's just sitting at the kitchen table with his child(ren), glancing at the cereal box in question. Not only does he have to deal with funny looks from his collegues because he only works part-time, and getting mocked by his friends for having to 'baby-sit' his own children (the horror), hence being unable to watch the footie with them in the pub around the corner.. nooooo... he doesn't even get addressed on a fucking cereal box!! I mean, really, that's not exactly encouraging young men to take on more responsibility for child care, innit?

But seriously, how difficult could it be? The change from "Mothers" to "Parents" would not impact on the price of printing. And, as I saw on your website in retrospect, you do have a picture of a whole family including a dad**, doing the breakfast thing, so it's not like you're totally unfamiliar with the concept... Just a little something to think about next time you re-design your cereal boxes, maybe?

Sincerely yours,
Angry Pedantic Bitch with no Life

*no, I am not going to comment on the joke that is trying to sell your sugary crack-laced cereal as healthy..

**it being a German website means the whole family is obviously blonde but that's an issue for another time..

hungry city

2009-02-18T01:12:00.002Z

he roams the neighbourhood, always restless, always staring at the wrappers on the ground. always hungry, longing for something he can't define. but it smells like spring, so that's something. and for a moment right there he feels okay. these streets are a landfill. it's getting dark, and this grey phase is the worst. he stands in front of her house for ten minutes, yet he doesn't knock and choses the usual routine instead. he remembers his cracked lip and the way it burned the night before. but it's too late now. he tells himself that there is some purpose to his plan, a disconnect from relentless introspection. or if not that, then at least temporary saturation and mental anaesthesia. he is angry, always fuming. he is a cloud of smoke and spit, and sometimes he turns into a hurricane. a run would be good maybe, but would he want to express the anger, he would have to sprint an entire marathon. and with this sleep deficit and that aching body even a short trip to the gym is very unlikely. his body becomes his punching bag instead. at least he's still walking faster than anyone else out there, all these people who seem content just strolling along. he wonders why he never felt like them but there are no answers. where his chronic distress originates from, he doesn't know. any reason will do as an excuse, but the root cause remains occluded.

the next day, he was back at the door. because no matter how wide the river of snot was going to be, it was better than the night before. better than being alone.

A short Intro to Dementia with Lewy bodies

2009-02-09T23:29:00.003Z

Introduction

Until the mid 80s Dementia with Lewy bodies (DLB) was thought to be rare, but it is now recognized to be the most common type of dementia following Alzheimer’s disease (AD), accounting for up to 20% of all cases of dementia. DLB appears to be slightly more common in men than in women. Lewy bodies, the hallmark of DLB, are small cytoplasmic protein inclusions infamous for their prominence in Parkinson’s disease (PD). In fact, DLB displays clinical and pathological overlap with PD and Parkinson’s disease dementia (PDD).

Overlap with Parkinson’s disease and Alzheimer’s disease

By convention, DLB is usually diagnosed if cognitive disturbances surface within one year of the onset of parkinsonian symptoms or even before onset of parkinsonism. In contrast, the term PDD is used if parkinsonian symptoms predominate. The idea that PD, PDD and DLB are not truly distinct disorders but all fall within the spectrum of Lewy body disease has been gaining support. In fact, PDD and DLB were thought to be separate conditions but it now seems clear that they are clinically, pathologically and psychologically identical.
Furthermore, patients with DLB often additionally present with varying degrees of AD pathology and vice versa (then called LB variant of Alzheimer’s disease). Despite differences in the brain areas predominantly affected and the genes implicated with DLB and AD, the frequency of co-occurrence of these disorders far exceeds chance. On one hand, the major culprits in DLB and AD, e.g. alpha-synuclein, beta-amyloid or tau appear to facilitate one another’s aggregation; on the other hand the increased co-occurrence could possibly be explained by a non-specific defect in dealing with e.g. oxidative stress as compared to age-matched controls.

Symptoms and Pathophysiology

DLB leads to cognitive impairment affecting memory, attention and visuo-spatial deficits, which is somewhat different from cognitive dysfunction encountered in AD. For example, DLB is clinically characterized by well-formed visual hallucinations, agitation and fluctuations in attention and alertness, thought to result from loss of cholinergic neurons (e.g. in the basal nucleus of Meynert), and identifiable through daytime drowsiness or staring into space for extended periods of time. Fluctuations in cognitive ability and attention are a relatively specific feature of DLB.
Memory impairments are also of a different nature, with patients suffering from DLB suffering less anterograde memory loss. In contrast, executive function deficits and extrapyramidal symptoms generally occur sooner in DLB than in AD.
As mentioned, parkinsonism is usually also observed to varying degrees, caused by depigmentation and neurodegeneration of the substantia nigra and disruption of nigrostriatal dopaminergic neurotransmission, as well as cerebral atrophy. Depending on disease subtype, progressive accumulation of alpha-synuclein- and ubiquitin-positive Lewy bodies can be seen in the brainstem, the limbic system or cortical and subcortical regions.

Genetic Risk Factors

The causes for neurodegeneration and accumulation of a-synuclein in DLB are not well understood. Oxidative stress, impairment of the ubiquitin proteasome system and mitochondrial dysfunction are all thought to contribute to neurodegeneration. Posttranslational modifications of a-synuclein such as phosphorylation, sumoylation and oxidation are thought to contribute to the conformational changes that lead to a-synuclein accumulation in LBs, but the reasons why these cellular changes occur remain largely unknown.
Rare cases of familial DLB have been reported and a number of genetic mutations have been identified that increase the risk of being affected by this type of dementia. These might eventually inform us on the underlying causes of neurodeneration. DLB is not only characterized by clinical variability but might also display genetic heterogeneity comparable to that of PD. Some family members in the kindreds harboring a-synuclein locus triplications also displayed DLB phenotypes. In addition, Zarranz et al (2004) investigated the high rate of DLB occurrence in a Spanish family and found the missense mutation E46K (Glu46Lys) in alpha-synuclein to segregate with the disease.
Mutations of leucine-rich repeat kinase 2 (LRRK2) have also been implicated in familial DLB, in addition to a novel locus on chromosome 2q35-q36 (PARK11). Recently, mutations in the glucocerebrosidase (GBA) gene, which are normally oddly enough causative for Gaucher disease, have been found to be associated with DLB (and PD). Additionally, the e4 allele of apolipoprotein E, the major genetic risk factor for AD, has been found to be positively associated with DLB.

Treatment and Prognosis

The symptoms associated with DLB can be treated with a variety of medications. Acetylcholinesterase inhibitors, for example, are the first line of treatment regarding hallucinations and agitation. Failing that, atypical neuroleptics may be administered, while typical neuroleptics should not be used. Contrary to patients with PD, most DLB patients do not respond well to dopamine supplementation (L-dopa, carbidopa), but in some motor function may be improved. Depression, which is quite common in DLB patients may be treated with SSRIs.
However, DLB is a progressive neurodegenerative disorder which leads to earlier mortality, and progression may be faster than that of Alzheimer’s disease. Ultimately, patients die from complications of immobility, poor nutrition, or asphyxiation due to swallowing difficulties.

Cure

None. Yet..

:P

References

Beyer K (2006) α-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers. Acta Neuropathol 112: 237 - 51.

Bonifati V (2008) Recent advances in the genetics of dementia with lewy bodies. Curr Neurol Neurosci Rep 8: 187-9.

Farrer M et al, (2004) Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol 55: 174 - 9.

Gan-Or Z et al (2008) Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurol 70: 2277-83.

Heidebrink JL (2002) Is dementia with Lewy bodies the second most common cause of dementia? J Geriatr Psychiatry Neurol 15: 182 - 7.

Jellinger KA (2003) Neuropathological spectrum of synucleinopathies. Mov Disord 18, Suppl 6: S2 – S12.

Lippa CF et al, for the DLB/PDD Working Group (2007) DLB and PDD boundary issues – diagnosis, treatment, molecular pathology, and biomarkers. Neurol 68: 812 – 9.

McGeer PL & EG McGeer (2008) The α-synuclein burden hypothesis of Parkinson disease and its relationship to Alzheimer disease. Exp Neurol 212: 235-8.

McKeith IG et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies: report of the consortium on DLB international workshop. Neurol 47: 1113-24.

Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophysiology of Parkinson's disease. Annual Review of Neuroscience 28: 57 – 87.

Singleton AB et al (2003) α-synuclein locus triplication causes Parkinson's disease. Science 302: 841.

Tsuang DW et al (2002) Familial dementia with Lewy bodies - A clinical and neuropathological study of 2 families. Arch Neurol 59: 1622 – 30.

Zarranz JJ et al (2004) The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55: 164 – 73.

...and, admittedly, one eMedicine article :/

...red links courtesy of Wikipedia.

blatant self-advertising

2009-02-09T10:32:00.005Z

i've recently installed the 'follower' gadget but look at how sad and small it is...

so, if you want to make a blogger happy today, just scroll down a little, take a look at my sidebar and click 'follow..'

thanks!

blogger's block

2009-02-07T23:52:00.004Z

i don't like my blog anymore. i don't like the way it looks (boring), don't like my posting frequency (f -> 0), don't like the quality of my posts (poor).

the trouble is that over the past couple of months i've found myself having less time to sit down and write a carefully crafted blog post while at the same time aiming to write better, more interesting posts. so i outsourced my sharing needs to friendfeed, in order to prevent the accumulation of linkdumps that no one reads. i also told myself i would stop writing about anything unscientific, which just lead to increased dissatisfaction with my blog whenever i didn't stick to that rule (and of course all of a sudden all i could think about were unscientific ideas for posts :p). the result is that the average number of posts per month has dropped from ~13 to ~5 since last july - and with a few rare exceptions my posts have been pretty mundane and not very original.

for a while i was considering giving up blogging alltogether, but there are still a bunch of underdeveloped ideas infiltrating some of my neural networks, and it's generally been nice to have some sort of personal space on the web, too...

i'm not sure what i was trying to achieve by writing this down or how i can change things. maybe i'm hoping for some understanding by the few poor souls who are still subscribed to my blog or pop in every now and then. maybe i should let myself write whatever i like for a while, without judging the relative read-worthiness of my posts, in order to get back into the flow. maybe i should just start off by making changes to the layout or finally updating my horribly outdated blogroll.

in any case i don't want to give up on the whole blogging experience just yet, even if it frustrates me at the moment. well, we'll see what happens. hope you'll stay tuned..

(just jack - writers block)

on toothbrushes (and oxytocin..)

2009-01-20T23:42:00.007Z

There's a new toothbrush in my cup by the sink. It makes me a bit uneasy, this toothbrush, and I'm not sure I can say why. It might have been the speed with which it appeared, after six weeks it was suddenly there, not asking for permission.

No, this toothbrush doesn't make apologies for its presence. It seems to feel right at home, next to mine, and I suppose that's a good thing..

An hour or so after the toothbrush had already taken up residence in my cup, he asks me if I minded. No, I don't mind, I say. How do you tell someone that their toothbrush isn't welcome, anyway? Answer: You don't.

I tell myself the toothbrush is a good thing. No one wants to be alone, after all, toothbrushes being no exception. I should be happy instead of eyeing it up like an intruder every time I'm in the bathroom.

Anyway, it's too late to speak my mind now. "Can you please take your toothbrush home with you again? I don't even know yet how many cavities you've had as a kid." - You can't say that..

edit 02.02.09: ...or maybe you do. :(

how science can benefit humanity...

2009-01-16T18:19:00.001Z

twelve months of psique

2008-12-25T19:44:00.002Z

i'm feeling stupid yet want to blog something - time for a meme. i came across this one @ drugmonkey and a blog around the clock a few weeks back and liked the idea. hence here you have it, the first sentence of each month's first post for 2008:

january: interesting review about the different mechanisms of alternative splicing and how alternative splicing is employed to influence development of the nervous system as well as synaptic plasticity eg in LTP.

february: in other news, check out the newest nature issue - i only have access to the correspondence section but damn - cognitive enhancement, modafinil, and "humans have always tried to improve their condition" among others.

march: yang et al: ciliary neurotrophic factor mediated dopamine D2 receptor-induced CNS neurogenesis in adult mice.

april: usually i try to group interesting abstracts according to a general theme, say neurodegeneration, depression, addiction, pharmaceutical developments and the like... these are just a bunch of cool abstracts that didn't really fit in anywhere.

may: just wanted to let you know that i've been lazy and decided against summarizing the rest of the review.

june: α-synuclein, a small highly conserved 19kD protein that has been implicated in a number of neurodegenerative diseases, belongs to a protein family including β- and γ-synuclein, first identified in the electric organ of Torpedo californica, as well as in bovine and songbird brains.

july: the ouroboros blog turned two recently (belated happy birthday!!) and chris just started a new blog carnival, called hourglass, with topics ranging from caloric restriction over tissue engineering up to brain health.

august: it's funny how sometimes you feel welcome in this place and the next moment you're all alone.

september: now just keep your word on these issues like all the good politicians do (*snicker*), and i might actually start to like you.

october: dear solitaire, there's something i need to tell you...

november: as blasé as i have been for the past months regarding the presidential election, mainly because: hey, it's not my country, is it? why should i care just because we're talking about the almighty US of A here? i can't help but feel a bit excited now, a bit anxious too.

december: so world AIDS day draws to a close, at least in this time zone.

submissions wanted for hourglass VI

2008-12-05T09:44:00.003Z

next tuesday chris at ouroboros will be hosting the 6th edition of hourglass. hourglass is a monthly blog carnival devoted to the biology of aging.

submissions are being collected right now, so if you would like to contribute and your post(s) loosely follows the description below, write to [hourglass.host][at][gmail][dot][com]:

"topics of posts should have something to do with the biology of aging, broadly speaking — including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. if in doubt, submit anyway."

all prior editions and the hourglass "mission" statement can be found here.

ways out of the energy crisis - part I

2008-12-03T10:48:00.001Z

Worried about fossil fuels running out? Don't be! Here's how to make coal in ten easy steps:

1. Get drunk.*
2. Return home hungy.
3. Preheat oven to 220°C.
4. Remove a pizza from its packaging.
5. Place pizza in oven.
6. Set a timer for when the pizza is supposed to be cooked.
7. Fall asleep on the couch.
8. Sleep through the timer beeping.
9. Wake up to the sound of the fire alarm and neighbours frantically ringing your doorbell.
10. Et voilá: You should now have a nice round coal briquette waiting for you in the oven.

*You'll see why this is necessary in steps 6 -8.

...

world AIDS day

2008-12-01T21:29:00.004Z

so world AIDS day draws to a close, at least in this time zone. i hope you all wore your little red ribbons.. seriously though, what's the point of world AIDS day, if not to ease our pretentious little minds, so we can forget about the 8000 people dying of AIDS each day, every day - mostly because they can't get the education and medication they need.

also... still no cure? come on.

where are we going?

2008-11-23T22:33:00.005Z

what is going on? there's no sudden metamorphosis to be seen here but things are changing.. about time too.. i don't know what's going on. you'd think that once you're past puperty, self doesn't change that much. well, seems like the brain actually is plastic longer than you'd think - is that a universal phenomenon or does it come with the will to change (or the ongoing realisation that the current status quo is inacceptable?) people develop... (why is it not called personal mental evolution?) it's great to see in younger siblings, it's at the very least interesting to see in oneself. does any of it matter in light of the greater scheme? what is the greater scheme anyway? there are certain people in this world, whose every move gets monitored and evaluated.. i am not one of them, never will be. yet.. it's difficult to believe that personal development doesn't account for anything. is humanity growing old (and wise)? seriously, do we know where we're going? or do we continue to rely on world leaders on telling us where people are going? people be dumb; i know that. but people evolve. about time we all evolved; somehow.

hourglass V

2008-11-11T17:15:00.001Z

Welcome to the fifth edition of Hourglass, a blog carnival about the biology of aging :)

Let's get started right away with a post entitled „On Risk and Acting Appropriately“ on Fight Aging!, which appeals to our rational side, making a case for aging research. While this may seem like preaching to the converted, given the nature of this carnival, the points are nontheless worth (re-)considering to remind ourselves why aging research is important. When trying to think rationally about potential harm, it is useful to keep the following four points in mind (orginally postulated by the bioethicist):

1. The certainty of the harm (e.g. 0.1% vs 70% chance)
2. The severity of the harm (e.g. broken leg vs death)
3. The likelihood of mitigating the harm (e.g. 0.1% vs 70%)
4. The cost of mitigating the harm ($1 billion vs $1 trillion)

Needless to say, aging scores pretty high on points #1 and 2 (100% and most severe harm possible, respectively). So why are aging or the postponement/elimination (for the optimistic types) thereof not bigger priorities in our society? As pointed out by Reason, part of the answer may lie in the widespread belief that there is not much to be done about aging. Ongoing studies with animals and treatments such as caloric restriction, some of which I will come back to later, show however that this is not the case. In addition, the apparently high cost of aging research needs to be put into perspective. SENS for example, wishes to spend 1 billion dollars within the next 10 years on longevity research. Sure, that's a lot of money, but what about the 148 billion dollars Alzheimer's disease alone is thought to cost the States each year...? In light of these points, it becomes clear that the lack of support for aging research is just a tad bit irrational.

One particular issue that needs to be addressed in gerontology, which is very dear to my heart, is the continual cognitive decline as we get older. As more people are reaching an older age, and society and our way of life are becoming increasingly cognitively demanding, we are in dire need of ways to keep our brains fit and healthy. Alvaro at SharpBrains brings forward a interesting proposal to create a „Global Consortium for Neurocognitive Fitness Innovation“, an initiative which would provide a bridge between cognitive neuroscience (but I would assume other neuroscientific subdisciplines would play a vital role as well), gerontology, and general preventive healthcare. More specifically, Alvaro envisions the long term collaboration of a „100 universities, policy-makers, healthcare/insurance providers and developers of technology-based neurocognitive assessments and training tools“. Goals would include raising public and professional awareness of the considerable malleability of our cognitive capacities; defining standards on how to assess cognition and the validity of interventions, as well as publicizing ways of increasing brain fitness and preventing neurodegeneration tailored to individual needs, and proposing new avenues for research.

Speaking of research... no biogerontology carnival would be complete without mentioning mitochondria, the free radical theory of aging, or calorie restriction ;-) The mitochondrial electron transport chain is thought to be the major generator of reactive oxygen species (ROS), which are implicated in general aging-related tissue damage as well as in specific disorders such as Parkinson's disease. Calorie restriction (CR) appears to significantly reduce the level of ROS generation, and apparently so does mitochondrial uncoupling (the bad excuse for a picture below is supposed to exemplify uncoupling by natural uncoupling proteins e.g. UCP1 and drugs like 2,4-dinitrophenol (DNP)..).

At Fight Aging!, Reason put together a summary dealing with mitochondrial uncoupling, CR and life extension. In one study, mice overexpressing UCP1 didn’t show an increase in maximum life span, although they were more likely to reach said maximum, possibly because these mice were generally not as affected by common aging-related diseases as control mice. In another study, CR increased expression of UCP2 and 3; transgenic overexpression of UCP2 & 3 slightly increased survival, but lack of either didn’t have any overt consequences. Hence, it remains to be seen what differences there are between natural uncoupling proteins and DNP, which does extend life span according to a recent study described by Mikeisnt, a new contributor to Ouroboros. While DNP was deemed too dangerous for human use due to risk of overheating, the mice in the study showed no change in body temperature. These mice did, however, show several characteristics of CR mice, such as lower levels of free radicals, lower blood glucose, triglycerides and insulin, and an extended lifespan, all while eating just as much as the control mice did – suggesting that mitochondrial uncouplers mimic the effects of calorie restriction.

Another way of mimicking CR might be achieved by rather unusual means, namely forgoing the ability to smell. In “Stop smelling the roses – and live longer?”, Ward Plunet of brainhealthhacks.com describes recent efforts to understand the connection between CR, olfaction and life span. It seems that prohibiting olfaction pharmacologically, by ablation of olfactory regions or genetic manipulation can result in an extension of life span, at least in C. elegans and Drosophila. Interestingly, CR and blocking olfaction appear to act in synergy, increasing life span most effectively when applied together, while exposure to food odours is capable of reducing the positive effects of CR to some extent. The obvious question is whether losing the sense of smell could also extend life span in humans. Failing the possibility of clogging up people’s noses, Plunet proposes a straightforward test – one could compare the life span of anosmics, who are people that have chronically lost their ability to smell for a variety of reasons, to carefully matched controls. Whether the inability to stop and smell the roses is a sacrifice people would be willing to make for a slightly longer life is obviously a different story, but personally I wouldn’t mind too much...

Alas, this is the end of Hourglass V, which has hopefully turned out to be an interesting, albeit maybe slightly too long, read.. Anyway, thank you very much for reading! I’m looking forward to the next installation; the only trouble with that is the current lack of a host – so if you’re interested in hosting Hourglass VI in December, please contact Chris Patil.

hourglass V is coming up

2008-11-07T07:06:00.004Z

in a mere 5 days i'll be hosting the fifth edition of hourglass here at psique. hourglass is a monthly blog carnival devoted to the biology of aging, biogerontology and the likes, that was set up by chris patil of ouroboros.

we're still looking for submissions, so if you've recently written (or would like to write) a post loosely fitting the below mentioned scheme, write to [hourglass.host][at][gmail][dot][com]:

"topics of posts should have something to do with the biology of aging, broadly speaking — including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. if in doubt, submit anyway."

former editions can be found h. e. r. e. :)

we're also looking for someone to host the next edition of hourglass, coming up on the 9th of december i believe, so if you're interested please contact chris.

i've never hosted a blog carnival before, so i'm pretty excited about the upcoming installment and i hope you'll come back next week to check it out !

so tomorrow is the big day, eh?

2008-11-03T21:29:00.002Z

as blasé as i have been for the past months regarding the presidential election, mainly because: hey, it's not my country, is it? why should i care just because we're talking about the almighty US of A here? i can't help but feel a bit excited now, a bit anxious too. i've never been a huge fan of obama, and mourned clinton's failure to win the primaries (go ahead, call me sexist..), but i cannot for the life of me picture mccain doing the country or the world any good. as has been said all over, we'd just end up with a third term of bush. and then he brought palin up on the plan, the show was over. i don't think i need to explain to anyone what about her makes me cringe (so there, not sexist after all..), hell - if you're educated enough to read this and haven't fallen on your head too often as a kid you are bound to realise how thoroughly unsuitable this woman is for becoming vice president.. as to obama being labelled an intellectual elitist, i can't help but wonder why you wouldn't want someone way smarter than you to run your country? since when is it good to be thick as moose skin?

but i digress... all i wanted to say is that i would really look forward to obama's presidency if the american people so will, i'm curious about what he would/could do, if after talking the (change) talk, he can walk the walk. it feels like he could bring fresh exciting times, usher in a new long-overdue era, whereas mccain would be bound to make me yawn at best, and puke at worst. and just imagine him dying.. (on second thoughts, don't. it's worse than imagining being trapped in a butcher's walk-in freezer). seriously, what the US and the world need right now is a young-minded, modern, intelligent and sensible president. it's the 21st century, for crying out loud.

so i just hope the people of the states will make the only right decision there is to make tomorrow. i would if i could, most of the world's citizens would if they could (even the daft british lad on radio 1 today who didn't get that despite being 19 he cannot actually vote in this election even though it probably got more media coverage than the last 3 british PM elections combined). go out and vote for senator barack obama. pretty pretty pretty please.

kampavata

2008-10-29T07:09:00.004Z

'kampavata' is the name under which parkinson's disease was described in ancient indian ayurvedic medicine (manyam, 1990). i find it quite cool that even hundreds of years ago, when nothing was known about the pathological and molecular mechanisms behind parkinson's, 'kampavata' was treated with a plant, mucuna pruriens, which was in retrospect shown to be a source of L-dopa (katzenschlager et al, 2004), a dopamine precursor that remains to be the main-line of treatment to this day.

on fear and aging

2008-10-13T23:47:00.000+01:00

i was never afraid of death per se; i know some people are but it was never really an issue for me. maybe i've just never gotten the hang of life, or maybe it's due to my admittedly simplistic belief that the moment you die, you don't actually remember ever having existed in the first place. it would certainly be nice to be able to choose when to snuff it (and i would be interested in seeing if, should life extension ever become a serious business, euthanasia for healthy elderly's could be legalised and at what age people would choose to die). but living 'forever'? life isn't actually that great, so thanks, but no thanks.

one thing that i do find myself being increasingly afraid of is aging. of course, you say, all the diseases associated with getting old.. cancer, strokes, heart attacks and diabetes, alzheimer's disease, rheumatoid arthritis and osteoporosis sure don't sound like fun. but it's not even that. of course i am weary of the pain and suffering associated with these illnesses (and i am afraid of the physical pain that may precede death..). but i am also fairly optimistic that medicine will have advanced enough in the next 30 years or so to keep these diseases at bay or at least delay their onset substantially. i am also, albeit naively perhaps, counting on having good health insurance in later life, which will make access to - by then hopefully also more affordable - effective treatments more likely. in addition, there seems to be a kind of blissfully ignorant attitude towards disease when you're still a teen/tween.

but maybe it's exactly this ignorance that has been slowly starting to fade away in the last year or so. there is one thing that i am increasingly afraid of, and that is aging. i don't mind the wrinkles on my forehead progressing (and they are!), but rather i get really scared about the prospect of not being able to move as quickly as i would like to one day, or not learning as fast as i used to. it's difficult to explain what exactly scares me, but i can certainly feel the fear getting stronger. it manifests itself in curious ways.

i have, for example, developed a great dislike for old people. i feel bad about it, because obviously it's not their fault for being old, but at the same time the aversion is so strong that i can't cognitively curb it. it's not a fault of my character i hope, it's just that old people remind me of my fear. when i see an old person walking, bent over, shuffling, slowly maybe even limping a little; when i hear them talk, slowly again, disjointed like a radio with bad reception, raspy or coarse; when i see their frail, small, wrinkled, dry or big, swollen, sluggish bodies.. i cringe a little, and quickly try to walk away from the feeling of disgust that overflows me inside.

unfortunately this doesn't just happen with strangers i see on the street. my own grandmother, a hard little woman in her early eighties, who was always a very active person (she went on numerous holidays with my family and worked in her own flower shop until her mid seventies), has deteriorated in recent years in a way that makes me very uncomfortable when i'm around her (which i am very very seldomly..). there is nothing obviously wrong with her, at least not when judging from physical check-ups and MRI/CT scans. yet she did developed some mild, apparently age-related form of dementia and also had to be treated with psychopharmaceuticals for about a year because she was getting very malicious and aggressive. now she's become eeringly quiet (she's no longer on any psychoactive meds), likes to watch tv more than ever, avoids company and has generally become a fraction of herself. she was always very proud of her morning gymnastics routine, now she barely leaves the house, has become frail and shrunk at least an inch. she is now what my mother may become in 30 years, and i may in 60 - and this nightmarish image of the future scares me so much it mutes whatever compassion i may have for my grandmother, makes me avoid even thinking about her.

likewise, i am starting to worry about my mum - are the small moments of confusion, for example when she's in a new city or supermarket or roundabout, signs of mild cognitive impairment? or is she just getting old? as above, i get agitated and impatient when she has one of her moments; in a way it would almost be better if there was some known clear-cut reason why she's not as mentally agile as she's always been (my mum, as well, has always been a very active, smart and independent woman). just two years ago, one could have trusted mum blindly to be able to navigate her way around a new city with no hesitation - now, i wouldn't be that sure. and she complains herself sometimes, that things are getting overwhelming and too much. given her current lifestyle that is not surprising per se, and it would be good if she cut down a little; but it's a discomforting thing to hear from someone who always needed to have 10 active projects going on at once, who always looked for new challenges and never complained of being tired. what is it that's making her tired now, if not aging?

it is precisely this that i am so afraid of. not death, not disease; but being forced to slow down because the body and the brain are getting old. sure there are exceptions, but these remain rare. and i feel this issue is not addressed enough in general. it's always about a cure for this or that, but aging in and of itself is considered a normal part of life. and i don't know, maybe it is, maybe it has to be.. - but isn't it scary as hell?

i ♥ blue brain

2008-10-12T16:27:00.003+01:00

h/t: mind hacks

an open letter to solitaire

2008-10-10T21:59:00.003+01:00

dear solitaire,

there's something i need to tell you... we had a lot of good times together these last three months (and before that too, a long time ago) and you know i love you very much, but... i just deleted you from my computer (or at least whatever traces of you i could find). i'm sorry, but i just have to move on, you know? there's a PhD to be done, which is demanding more and more of my attention; there's friendfeed and google reader complaining about backlogs, there's countless journal articles to be read, new people to be met, exercise to be done, there's all sorts of stuff..

you've always been very good to me, and i appreciate that. you were always there for me whenever i was tired, sad, bored, or lonely. but you know very well that you're also an enabler, making me stay in a situation i am not happy with, precisely by offering comfort in the way you do. and since my scores are never going to surpass the global champions, it's unlikely i could ever make a living out of my passion for you.

i'm sure i'll try to get you back somehow sooner or later. failing that i might temporarily settle for some cheap online substitute that won't in any way compare to your vista goodness.. i just hope you don't take this personally, because really this isn't about you at all - it's about me and my own shortcomings (although, to be honest, before we started using the external mouse i was getting a bit frustrated with you since you wouldn't let me surpass my high score..).

anyway, i just wanted to let you know.. i wish you all the best..

love,
laura

if only our future always looked so bright..

2008-09-22T21:23:00.002+01:00

linkage disequilibrium

2008-09-22T07:39:00.002+01:00

--repost--

After having sat in last week's journal club absolutely clueless, something I found incredibly frustrating and irritating, I decided to drop PINK1 for the time-being, and try to read some of the theoretical stuff around genetics first. I figured a good place to start would be the notion of 'linkage disequilibrium', or rather, that just happened to be the last reference of the McQuillan paper.

While the wiki on LD still made some sense to me, the paper by Vitard et al (2005) did considerable less so. But basically, LD is as measure of how the actual recombination of given alleles A and B differs from the predicted random recombination frequency. This can be influenced by inbreeding (non-random mating), close physical proximity of the alleles on the chromosome, small enclosed populations and other things. For example, extended LD is often observed in areas surrounding alleles that are evolutionary advantageous (e.g. resistance to Malaria). LD tends to decay over generations, but abovementioned factors can slow decay. Vitard showed that LD is more common among rural Scotish populations, especially on islands, and relatively less common in urban populations. This points to LD in the investigated cases being mainly due to external factors (eg population structure) and less due to intrinsic interaction between given alleles (like a genetic advantage for having both or sth).

There were lots of table and calculations that I didn't get, but after all this is pretty much the first LD-paper I've read in my entire life. (Dramatic, no?)

--- This is likely to be updated as I read some more stuff ---

Some random definitions I'm likely to forget:
D = measure of linkage disequilibrium. D = 0 is no LD, D = 1 is the max value
Fis = measure of departure from random mating within a population (Wright)
W = empirical measure of LD between pairs of multiallelic markers (W is apparently less sensitive to factors such as sample size and allele numbers)

spinal cord injury treatment

2008-09-20T22:35:00.002+01:00

Here's a bunch of sites I found regarding spinal cord injury, treatment, rehabilitation and research, which I had to compiled today for semi-personal reasons - and I figured I might as well put them on here; maybe they'll come in handy for someone. I'm anything but an expert in the field, but tried to pick out resources that looked like they have something going for them. Obviously there's many more out there, a real jungle.

Selected Clinics & Rehabilitation Centers:

List of the Top Rehabilitation Centres 2005

List of 'Model Spinal Cord Injury Systems' (Hospitals/Centers devoted to spinal cord injury treatment & rehabilitation)

Mayo Clinic (treatment, rehabilitation, research and clinical trials)

Karolinska Institutet Hospital, Spinal Cord Injury Centre (Stockholm)

Rehabilitation Institute of Michigan

Center for Spinal Cord Injury Recovery

Northwest Regional Spinal Cord Injury System (Washington)

Magee Rehabilitation

Boston Medical Center

Feinberg School of Medicine

Kessler Institute for Rehabilitation

Craig Hospital

Research:

Information from the ICCP about experimental treatments for spinal cord injury (PDF file)

List of Clinical Trials currently recruiting patients with spinal cord injury

Proneuron phase 2 clinical trial seeks participants w SCI less than 14 days old, macrophage-based therapy
Mount Sinai Spinal Cord Injury Model System (NY)

Stem cells:

University of Wisconsin (people who have worked with stem cells in the past)

List of researchers working on transplanting olfactory cells (apparently with quite some success)

University of California, Irvine - research is being done on spinal cord injury and stem cells

Stem Cell Pharma, Inc (Nevada) plans to open a stem cell centre, treating among other things spinal cord injuries

Stem cell research at the University of Michigan

San Diego Consortium for Regenerative Medicine

More Information:

Christopher&Dana Reeve Foundation

National Institute of Neurological Disorders & Stroke (Spinal Cord Injury Info)

National Rehabilitation Information Center

Brain&Spinalcord.org

National Spinal Cord Injury Association

runs of homozygosity in european populations

2008-09-19T07:37:00.000+01:00

--repost--

Elisa talked about a recent paper by McQuillan et al: Runs of Homozygosity in European Populations (2008).

I hadn't read the paper before journal club, and consequently didn't have a fecking clue what she was on about. Need to remember to ask Vicky or whoever else is presenting this week about the paper in advance. But in a nutshell...

McQuillan and colleagues investigated the length and occurance of runs of homozygosity (ROH) in the Scotish Orkney, mixed and main-land Scotish population, as well as in people from Dalmatian islands and Croatia. The interesting thing about the Orcadian population is that there has been very little immigration and lots of consangious marriages, hence the gene pool on the island is not very varied. This was evident from the Orcadians having longer and more frequent ROH (i.e. there were lots of instances where samples shared long (1.5-10MB) stretches of identical sequence. The important thing is that due to the inbreeding, most of these identical sequences are likely to be identical-by-descent. Now normally a term called Fped or Fplink estimates the amount of autozygosity, by pedigree analysis or running the PLINK software, respectively. McQuillan showed that their measure, Froh, is more accurate. More generally, McQuillan showed that shared ROH under 1.5MB in length are quite common, even when comparing the general population to more closed populations. Above 1.5MB the frequency drops more and more, and shared ROH between 5-10MB in length are unlikely to be found in large genetically diverse populations.

The other stuff escapes me at the moment...

NBIA-1

2008-09-17T07:45:00.002+01:00

Neurodegeneration with brain iron accumulation type 1 (NBIA-1; formerly Hallervorden-Spatz disease) is a rare, degenerative early onset movement disorder presenting with dystonia, muscle rigidity, spasms and ataxia, as well as cognitive decline. NBIA-1 is characterized by excessive iron levels in the globus pallidus and substantia nigra, as well as atrophy of the substantia nigra, the striatum and ventral tegmental area (Gregory & Hayflick, 2005).

The inability to regulate iron levels and increased oxidative stress appears to lead to neurodegeneration, demyelination and gliosis in the basal ganglia. In addition, iron pigment deposits, and swollen dystrophic axons, so-called axonal spheroids, which are immunoreactive for α-synuclein can be found in the globus pallidus, the SN, and the cerebral cortex (Galvin et al., 2000).

Abnormal peroxidation of the neuromelanin precursor lipofuscin may be responsible for the accumulation of iron, and malfunctioning of cysteine dioxygenase may lead to accumulation of cysteine in the basal ganglia. Cysteine is rapidly oxidized in the presence of iron, leading to the formation of free radicals and thereby potentially paving the way for cellular stress and cell death (Gregory & Hayflick, 2005).

In the majority of cases, mutations in the PANK2 gene (coding for pantothenate kinase 2) appear to cause defective cysteine metabolism, which may enhance iron accumulation (Jellinger, 2003). The discovery of mutations in the PANK2 gene pointed to the importance of the interaction between cysteine-containing compounds and iron (Zhou et al., 2001). Pantothenate kinase-associated neurodegeneration (PKAN) is inherited in a autosomal recessive fashion and starts early in childhood (Gregory & Hayflick, 2005).

Atypical NBIA-1, on the other hand, has no known genetic causes and occurs slightly later in life. Interestingly, neurofibrillary tangles containing tau and α-synuclein positive LBs as well as GCIs have been identified in cortical and subcortical regions of some adult patients (Saito et al., 2000; Jellinger 2003). It remains unclear what causes the accumulation of α-synuclein in PKAN, although oxidative stress is likely to play a similar role as in other synucleinopathies, and it has been shown that α-synuclein aggregates faster in the presence of iron (Ostrerova-Golts et al., 2000).

References

Galvin JE, Giasson B, Hurtig HI, Lee VMY, Trojanowski JQ (2000) Neurodegeneration with brain iron accumulation, type 1 is characterized by α-, β-, and γ-synuclein neuropathology. American J Pathol 157: 361 – 8.

Gregory A, Hayflick SJ (2005) Neurodegeneration with brain iron accumulation. Folia Neuropath 43: 286 – 96.

Jellinger KA (2003) Neuropathological spectrum of synucleinopathies. Mov Disord 18, Suppl 6: S2 – S12.

Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farrer M, Wolozin B (2000) The A53T α-synuclein mutation increases iron-dependent aggregation and toxicity. J Neurosci 20: 6048 – 54.

Saito Y, Kawai M, Inoue K, Sasaki R, Arai H, Nanba E, Kuzuhara S, Ihara Y, Kanazawa I, Murayama S (2000) Widespread expression of α-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protacted clinical course. J Neurol Sci 177: 48 – 59.

Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ (2001) A novel panthothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 28: 299 – 300.

progranulin, microRNAs and frontotemporal dementia

2008-09-12T07:31:00.000+01:00

--repost--

Huw gave a presentation on a recent paper by Rademakers et al, called "Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia" [open access]. It was really interesting, though I don't have any notes. Here's the abstract:

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR-DNA binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ~10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3’untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared to homozygous C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders.

Last but not least, a few papers which would make for good background reading:

Cairn et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114: 5–22. [open access]

Cruts et al (2006) Null mutations in progranulin cause ubiquitinpositive frontotemporal dementia linked to chromosome 17q21 . Nature 442: 920-4.

Bartel (2004) MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell 116: 281-97. [pdf]

Needless to say I haven't read them yet, although Bartel's review has been chilling in my computer for at least a year now... hey, it's a start! ;)

yeah.

2008-09-09T23:45:00.005+01:00

ht: chris

hourglass III

2008-09-09T21:58:00.005+01:00

soo... the third edition of hourglass, a biogerontology carnival, just came out at sharpbrains, and whatdoyaknow.. my recent, rather serious post about multiply system atrophy got a small mention.

other interesting stuff includes an intrigueing post about gene expression changes associated with premature aging and life-extension through caloric restriction, as well as the effects of exercise on aging. but there's much more, go check it out for yourself..

anne @ existence is wonderful will be hosting the next edition in october; so stay tuned :)

don't you love that feeling?

2008-09-04T07:28:00.002+01:00

a short intro to multiple system atrophy

2008-09-02T22:22:00.010+01:00

Multiple System Atrophy (MSA) is a rare sporadic neurodegenerative disorder with average age of onset at 59 years (+/- 7), and average duration being 7 years. MSA features alpha-synuclein pathology, parkinsonian symptoms as well as autonomic failure.

Depending on which brain areas are predominantly affected and corresponding symptomatology, MSA is categorized into two subtypes: cerebellar-feature predominant MSA (MSA-C) and parkinsonian-feature-predominant MSA (MSA-P), although in the past a Shy-Drager syndrome, a third subtype characterised especially by autonomic failure, due to preganglionic autonomic lesions, was also recognised (Gilman et al, 1999). Patients suffering from MSA-C display motor disturbances associated with deterioration of cerebellar regions e.g. progressive ataxia and poor balance, while MSA-P can be sometimes misdiagnosed as Parkinson's disease (PD), due to parkinsonian symptoms such as tremor and muscle rigidity resulting from degenerating of the nigrostriatal pathway. Imaging studies suggest cortical atrophy in patients with long disease duration, however, cognitive decline is not a major symptom of MSA (Yoshida, 2007).

The histopathological hallmark of MSA are alpha-synuclein-positive protein conglomerates which are predominantly oligodendroglial and commonly called glial cytoplasmic inclusions (GCIs). In addition, alpha-synuclein aggregates can be found in glial nuclei, neuronal nuclei and cytoplasm as well as in dystrophic neurites. Apart from fibrillar alpha-synuclein, GCIs also contain ubiquitin, and less consistently tau, tubulin, cycling-dependent kinase 5, microtubule-associated protein-5 and a number of other proteins (Yoshida, 2007). GCIs are most likely to be found in primary and supplementary motor areas as well as surrounding subcortical white matter. Other affected areas include the globus pallidus, internal and external capsules, pontine transverse fibers, and the cerebellum. In contrast to other synucleinopathies, inclusions also form in the autonomic nervous system. The distribution and density of GCIs depends on clinical subtype, disease severity and duration (Dickson et al, 1999).

The underlying causes for the occurrence of alpha-synuclein inclusions and brain atrophy in MSA remain unclear. Neuronal nuclear inclusions may form well before neurodegeneration becomes apparent, while cytoplasmic inclusions are more evident in later stages. Likewise, oligodendroglia bearing GCIs do not die immediately (Yoshida, 2007). However, the persistent presence of GCIs might be responsible for myelin degeneration, which in turn causes axonal dysfunction and in end effect neurodegeneration. In addition, neuronal death may be accelerated through accumulation of alpha-synuclein in the cytosol, for example as protofibrils, similarly as in PD (Wenning & Jellinger, 2005; Wakabayashi & Takahashi, 2006).

One problem in trying to elucidate the molecular pathology of MSA is that no familial cases which might have provided cues have been found to date. So far no correlation between SNCA polymorphisms and MSA has been found (Ozawa et al, 2006a) and in a recent study, Lincoln and colleagues (2007) failed to show the presence of SNCA gene multiplications in MSA patients. However, comprehensive whole genome association studies may uncover genetic causes for MSA in the future (Ozawa, 2006b).

Patients generally respond poorly to L-dopa, hence new disease-modifying treatments aimed at preventing alpha-synuclein aggregation and/or gliosis are needed.

References

Dickson DW, Lin W, Liu WK, Yen SH (1999) Multiple system atrophy: a sporadic synucleinopathy. Brain Pathology 9: 721 – 32.

Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK (1999) Consensus statement on the diagnosis of multiple system atrophy. Journal of Neurological Sciences 163: 94 – 8.

Lincoln SJ, Ross OA, Milkovic NM, Dickson DW, Rajput A, Robinson CA, Paparetropoulos S, Mash DC, Farrer MJ (2007) Quantitative PCR-based screening of alpha-synuclein multiplication in multiple system atrophy. Parkinsonism & Related Disorders 13: 340 – 2.

Ozawa T, Healy DG, Abou-Sleiman PM, Ahmadi KR, Quinn N, Lees AJ, Shaw K, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Josephs KA, Barone P, Tolosa E, Goldstein DB, Wenning G, Geser F, Holton JL, Gasser T, Revesz T, Wood NW, European MSA study group (2006a) The alpha-synuclein gene in multiple system atrophy. Journal of Neurology, Neurosurgery, and Psychiatry 77: 464 – 7.

Ozawa T (2006b) Pathology and genetics of multiple system atrophy: an approach to determining genetic susceptibility spectrum. Acta Neuropathologica 115: 531 – 8.

Wakabayashi K, Takahashi H (2006) Cellular pathology in multiple system atrophy. Neuropathology 26: 338 – 45.

Wenning GK, Jellinger KA (2005) The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathologica 109: 129 – 40.

Yoshida M (2007) Multiple system atrophy: alpha-synuclein and neuronal degeneration. Neuropathology 27: 484 – 93.

----

multiple system atrophy knol

now.., just keep your word...

2008-09-02T02:13:00.003+01:00

...on these issues like all the good politicians do (*snicker*), and i might actually start to like you.

say it isn't so...

2008-08-20T14:40:00.005+01:00

according to yahoo news (who apparently got their info from the AP) there's been a nice little survey done in germany that asked the question what men and women value most about their partners/look for in a partner (it's not entirely clear which way the question went as people where asked what they look for in partner but they were all in relationships).

here are the stats that got a mention:

45.6% of men want a woman who can cook well.
44.1% look for a woman who is good looking and well groomed.
43.1% of men like it when a woman 'eagerly performs domestic chores'.

fine, so about half of german men are not exactly at the forefront of progressive thinking. i'm not surprised. what about the women?

47.8% of women look for a partner who will care for them and protect them (from what? bears?)
33.8% like men who can take care of them financially.

wtf ladies?

guess feminists can just lean back and stop fighting for women's emancipation, self-sufficience and equal career opportunities because it looks like you're quite happy with being dependent, weak and generally medieval..

the results of the survey seem so outdated to me that i'm inclined to believe it might just be conservative propaganda. either that or something's terribly wrong with this country or something's terribly wrong with me and all the values i hold dear. anyway, good thing i'm getting out of here.

neuro/comp/sci/goodness

2008-08-16T00:16:00.006+01:00

smart and entertaining people talking about the brain, computing and the web - a perfect friday night..

jeff hawkins, personal favourite, on establishing a theory of the brain (ht: neuroanthropology).

kwabena boahen, on modeling better computers after our biological 'counterpart'.

kevin kelly, on the near future of the web and how it might become 'the one', an all-encompassing intelligent, nearly organic entity.

out of breath

2008-08-01T16:51:00.006+01:00

it's funny how sometimes you feel welcome in this place and the next moment you're all alone. the question is how much of yourself you let others see when temporarily abandoning hard-earned self sufficience. i'm leaving the hamptons today, and entering the prelude to a new life if you so will. i wouldn't mind the extremely stressful weeks ahead if it wasn't for my body starting to tell me to chill the fuck out and the fact that i will be on my own, and need to continue practicising being content with it. i'm not used to the 'work hard, play hard' routine yet, and although i appreciate the past weeks as excellent training, i'm afraid of reaching my limit before it'll be okay to do so. on the other hand, sleep deprivation is a beautiful thing, muting affect and making one's return to solitude and discipline easier to endure. certain things cease to matter when you're running on empty, i love that feeling.

warm & fuzzy

2008-07-26T19:32:00.005+01:00

sometimes the best things don't happen until the day is done. it's those rare one-on-one conversations that make life worthwhile, that reward for the pains of being conscious and aware. when a person you thought you knew reveals a new side of her, offers a new perspective and temporarilly lets you suspend the conviction that people are full of shit, when you talk till late on an endogenous high. likewise, it is almost therapeutic to talk about yourself and have your behaviour and 'how you are' understood for once, the pieces of the puzzle falling into place. at last, what better compliment is there than being told: "wow, it's really interesting how your mind works". - ditto, dear.

trippy summer

2008-07-23T03:57:00.003+01:00

i'm in a strange place right now. i spend my days (or rather nights) serving people food, carrying up to 90 dollars in my hands at a time as i try to juggle three plates and still walk somewhat gracefully. i work with around 25 people on a daily basis, not to mention customers. according to my own standards i am being pretty social, i even made some friends (if you consider the american/social networking definition of friendship). i am by no means eager to go to work every day, but i still do it. and it definitely feels very different from spending most of my time in front of the computer...

biogerontology carnival and a birthday

2008-07-10T13:48:00.004+01:00

the ouroboros blog turned two recently (belated happy birthday!!) and chris just started a new blog carnival, called hourglass, with topics ranging from caloric restriction over tissue engineering up to brain health. obviously urging you to go check it out!
hourglass will presumably become a monthly installment, and hopefully i'll manage to submit a post to it next time around.

song of the summer

2008-07-03T20:55:00.001+01:00

friendbot

2008-07-02T11:01:00.000+01:00

Cyanide & Happiness @ Explosm.net

the giant's shoulders

2008-06-30T11:41:00.004+01:00

a new blog carnival is coming up, about classic papers, scientists who did some really important, and big concepts in science, called the giant's shoulders. the first edition is scheduled for july 15th, and i'm already looking forward to it.

thanks to gg and coturnix for coming up with the idea.

news from the loser lounge...

2008-06-29T03:40:00.003+01:00

this is exactly why i put lindabeth's blog in my reader:

entertainment and 'choice'

although the post about women and men and society and me written recently has moved towards one extreme side of things (which i don't mind in the very least), i find it worthwhile to point to this very different kind of aspect of society/entertainment, which i was trying to point to in my post as well (albeit probably unsuccessfully).

so yea, ditto 100%.

(almost) weekend links XI

2008-06-27T07:12:00.010+01:00

when i went outside this morning the air smelled like it used to in hove, good thing the time has come to escape to the hamptons (no, we're not rich, just lucky) today. blogging may be sparse in the next 5 weeks due to frequent visits to the beach, getting huge tips (i hope!) from rich new yorkers, parties with my cousins and shopping sprees facilitated by the great US economy. but before i run away, here's a few links...

reality check: drugmonkey informs us that academic science is "not a care bears fucking tea party". and there i was, thinking that in research i'd be protected from evil elbows and could spend my life eating cream puffs. damn.

the grass is always greener... well, maybe not judging from em's short account (i hope there'll be more to come) of living in thailand.

anti-aging research: dominick has set up a new blog, where he continues to write very informative posts about, well you guessed it - anti-aging research (eg the role of telomers in cell senescence).

TED: loved this talk at TED by robert full, in which he describes how nature can inspire an artificial foot/leg capable of walking on almost any surface and up walls. high up on my to-watch: nicholas negroponte talking about OLPC. what's more, TED compiled a list of their top 10 videos.

the end of theory? wired's editor-in-chief chris anderson claims that thanks to ever-increasing computing and storage powers, the scientific method will need serious revision, and that setting up hypotheses, making models etc will become obsolete as it'll be enough to just observe huge datasets. i was sceptical, but didn't really feel educated enough to justify my opinion - so it's great to see i'm not the only one thinking that anderson is a bit off on this one.

phone sex: phillip toledano took photos of phone sex operators of all shapes and sizes, colour and gender, supplemented by short narratives. very very intriguing even if it makes you feel a bit like a voyeur into someone else's personality (ht: neuroanthropology).

fMRI: deric bownds summarises a nature article about the up- and down-sides of brain imaging here. personally, i'm getting tired of fMRI studies these days, especially when they 'prove' boring common sense stuff, or provide new fodder for straight homophobic sexist men (crappy headlines, anyone?)

primates: spain, usually not that high up on the innovative law-making scale, is granting certain human-like rights to apes. obviously i think that primates are needed in research (sad as it may be), but keeping monkeys in circuses etc is really unneccessary. so yea, way to go!

plants: flowers have feelings too! well, maybe not. but realising that they do communicate with one another (and animals) is still really cool. more at bayblab.

drugs: marc writes about changes in gene expression and drug addiction, prompted by a new study to be published in nature. in a nutshell: exposure to a number of drugs causes DARPP32 to be localised to the nucleus, obviously via dopamine, and leads to histone phosphorylation, thus expression changes - very cool stuff!

meeeeh

2008-06-25T23:44:00.002+01:00

was gonna change the design of my blog (including fancy tabs!) but it all went pearshaped. trying to learn code for 3h without actually consulting anyone can be very frustrating.

so yea. back to the old layout, except the temporary switch ate my widgets (including the sites and blogroll - which means manually putting in around 150 links again... yay!). also, it all looks like shit and i'm too tired to fix things now.

however, if anyone does know how i could add horizontal tabs to the blog without resorting to gecko&fly-like stuff (ie uploading a whole new template, which clearly didn't go too well...) nor the rather primitive looking tabs by hoctro (no offense, i just don't have the knowledge to change the design, hence picky), well... let me know and i shall virtually kiss your feet (if it actually works).

ps: yea, i'm aware of wordpress - but i wouldn't switch just because of some silly urge to have tabs.. (or would i..?)

Isabel Allende at TED

2008-06-25T17:42:00.003+01:00

a great short (18min) talk by the wonderful author isabel allende. it's amusing and it's sad, telling stories of allende's own life, and stories of some of the passionate, strong women she encountered; as well as about the suffering that especially women in poor countries are continueing to experience. she ends on a hopeful note.

digging in archives

2008-06-24T22:12:00.001+01:00

..Beauty in Neuroscience

"The hippocampus and the dentate fascia are adorned by many features with the pure beauty of the cerebellar cortex. The cells, like the plants in a garden – as it were a series of hyacinths – are lined up in hedges which describe graceful curves."

– Santiago Ramon y Cajal

contra physical control of the mind...

2008-06-23T20:52:00.007+01:00

these days i increasingly find myself reading feminist/progressive blogs, i'm not sure why. i guess i'm at a point in life where i'm looking for some (re-)definition of what it means to be a woman, now that i'll soon be turning 25, on the brinck of permamently moving away from home, without a significant other for the first time in nearly 9 years, consequently thinking a lot about relationships past and relationships future, starting to feel like i actually am a grown woman, and no longer a girl. maybe i'm looking for some guidance.

my interest first took off maybe a bit less than a year maybe when i started reading thus spake zuska, a blog that deals a lot with inequality between men and women in academia. now i haven't experienced any maltreatment myself thus far, possibly because the biological sciences are quite populated with females (why? because it is a 'soft' branch of natural science..?). but i've heard ancedotes from my mum, who is a quite high-up anesthesiologst in a quite high-up hospital as well as a very strong woman. it's also not easy to ignore the pay gap and other such things that are well documented. neither is it easy to ignore dipshits like summers, or my own 16y old brother sighing "ah, women and technology.." as soon as i fail to work out some car radio function in less than a split-second.

well, that interest of mine came and went - temporarilly went into hiding maybe. recently, as i've mentioned, i've found myself reading more again. this time it's a lot about women in the media (eg in ads like these), it's also about hillary clinton and the misogynistic tendencies of many that surfaced during her campain. and then it's also about sex, about misogyny in the bedroom, about porn and about rape. the trouble is that while i may get angry about eg unfair situations at work, or sexist ads and the like, and then sort of forget about it again - i can't do the same with shit like this, or this, or this. instead i end up in tears of rage and frustration over the violation of women and their bodies, which is not and cannot be excused by men being the physically 'stronger' sex and hence allowed to forage 'weaker' females like a predator in these seemingly intellectual and enlightened times.. and i am unable to put it aside like the other issues.

the reason for writing this (which may irritate some readers who've come to expect sciencey/geeky content) is this inability to simply start thinking about something else right now, and the lack of someone irl who i could talk to about it. it's all too easy to start resenting and hating all men, all porn - all sexuality even (and it's consequently difficult to inhibit this impulse), but i'm not sure that's the answer. specifically, i don't think that changes anything. and that is what's leaving me feeling very sad instead of angry now, not knowing what to do. what can a single individual with little experience and practically no influence on anything do? yea, guess i'm looking for guidance...

weekend links X

2008-06-21T21:22:00.002+01:00

the birth of the computer: george dyson gave an entertaining TED talk about the first computers (and the first geeks) in 2003.

word play: wordle lets you create and customise cool word clouds (like tag clouds) from any paste-able text. the longer, the better, i think. there's also a gallery of other people's clouds. ht: the great beyond.

parenting 2.0: is it possible to equally share parental and household responsibilities? in the NY times, lisa belkin writes about positive examples from hetero couples, what we can learn from homo couples, and about obstacles faced by parents who want to go 50/50 as well as sickening stats (even if both partners work full time, women still do twice as much housework as men - i mean WTF people?) ht: neuroanthropology (weekly roundup #16 is full of other good articles btw).

post-it notes 2.0: watch the short clip at the filter and be amazed. i'm not even sure this can be for real but me wants!

slide shows galore: at slideshare you can watch, upload and share presentations. there's everything from business over pregnant men to cultural stuff and science. remember when you had to do presentations with projectors and hand written foil slides? ht: wired how-to wiki.

diet, health, and weight: as per usual, there's a great list of articles over at neuroanthropology, this time about all things food & weight related. especially recommended: natural neuroprotection (DANA foundation) and unusual measures to curb obesity in japan (NY times).

california I: yay for homosexual marriage finally being legal. the photo series at dorothy surrenders (sorry for stealing the pic) is really touching. ht: shakesville.

california II: boo for 23andMe et al getting angry letters from up above - really? of course everyone is entitled to get their DNA sequenced. of course most doctors know as little about genetics as their patients, and hence are in no position to decide whether one may get tested or not. what makes me less eager to condemn the health department's action though, is that most people don't know what to make out of the info either, and without proper regulation it's all too easy for sequencing companies to sell approximations and predictions as real 'facts' with a tiny asterisk attached. maybe one could set up guidelines similar to those for pharmaceutical advertising (but better..)? also, the whole idea of sharing your SNPs with other people or 'finding other people like you' that 23andMe (ht: scienceroll) propagates is just silly.

new frontiers: how to go from pharma to venture capital? allan marchington and steven ryser talk about their transition in this nature reviews drug disovery article.

mind uploading, anyone? not anytime soon :p... mike at brainstimulant brought my attention to PetaVision, an attempt to model the human visual system. although this is really cool, just look at how much computing power (not in flops but in real space) they use while our oh-so-errorprone-and-imperfect brain manages to give us a pretty good approximation of how the world looks like with only what? max 150ml volume (wild guess) of visual cortex?

;)

2008-06-21T12:44:00.002+01:00

source: the filter.

the reader

2008-06-18T22:45:00.004+01:00

nicholas carr asks: is google making us stupid?

- this is not about outsourcing our knowledge, as carr merely uses google as a pin up for the internet as a whole, and makes a few very thought provoking observations along the way. so the question is really: is the internet making us all go ADHD?

personally, i don't find that reading long texts, books even, has become more difficult. what i have noticed though, is that jet skying on the surface instead of scuba diving in the sea of words, as carr puts it, has become considerable easier and more natural and seemingly more fulfulling. the trouble (?) is, that while information in print form is fairly linear, information on the internet is embedded in a freaking massive web. you get links in the text, recommendations for other articles/posts and the like, and you end up jumping from link to site, and yes - sometimes you never go back to the original piece because you find something seemingly more interesting on your way. on one hand, it's very useful to be able to look into the background of a given topic with a few clicks, as compared to say tediously searching out relevant articles referenced in a printed review paper. on the other hand, it's all too easy to get sidetracked and end up 'investigating' one small detail while forgetting the bigger picture.

the other problem is that the internet is overflowing with information and interesting things, and although one can try, i bet my eye balls it's impossible to ever read every article one either has to or would like to read, watch every video worth watching and listen to every podcast there is - at least not unless one has limited attention to begin with and a small, fixated area of interest. for anyone interested in a lot of different things, the internet is a both a blessing and a curse. on one hand, now you finally have access to all the info you could ever want (given the right subcriptions/memberships etc). on the other, the internet may create the feeling that you aren't reading enough and don't know enough - just because what you've read and what you know is but a tear drop in the ocean of information. i'm not sure this applies to everyone, since i suppose that reading the whole encyclopedia from A to Z might not have been everyone's childhood dream, and consequently not everyone feels bummed because they never managed to (likewise there may be some people who actually did read the whole damned thing and by virtue of their reading speed/intellect/lack of friends/free time have less of a problem in keeping up to date with all the info the internet provides), but i suspect that there are some people out there who know exactly what i'm on about. i for my part tend to skim tons of stuff, in the (false?) belief that if something should ever require in depth reading, i should be able to retrieve it with the help of a few keywords.

anyway, i only meant to raise awareness of carr's essay instead of ranting (damn you, read/write web!) because he obviously mentions a whole bunch of other important points and is generally much more worth your time. also, i've got a bunch of stuff left unread and it's getting late. thank google for reader :p

from psychology to viruses

2008-06-15T22:19:00.002+01:00

just a few interesting articles/reviews that i want to share but which don't fit neatly into any of my usual categories..

johnson et al: the strong, sensitive type - effects of gender stereotypes and leadership prototypes on the evaluation of male and female leaders. +++

gannon et al: rape - psychopathology, theory and treatment. (review) ++

kozima et al: children-robot interaction - a pilot study in autism therapy. +++

kuniyoshi et al: emergence & development of embodied cognition - a constructivist approach using robots. (i admit to understanding fuckall but this sounds v interesting) +++

natale et al: sensorimotor coordination in a 'baby' robot - learning about objects through grasping. ++

dombeck et al: imaging large-scale neural activity with cellular resolution in awake, mobile mice. +++

saunders et al: barriers in the brain - a rennaissance? (review) +++

feuerstein: presynaptic receptors for dopamine, histamine, and serotonin. (review) +++

salinas et al: molecular landmarks along the axonal route - axonal transport in health and disease. (review) ++

liu & shuai: regulation of the sumoylation system in gene expression. ++

cho: the genetics and immunopathogenesis of inflammatory bowel disease (review, free full access). +

de vries & berkhout: RNAi suppressors encoded by pathogenic human viruses. ++

screw sex & the city...

2008-06-14T20:06:00.006+01:00

..which is invading germany at the moment, as the female panem et circenses counterpart to the UEFA Euro.

Instead: Science & the City podcasts. Lots of them. I listened to about half of the ones currently available and these are the ones I liked best... hope you'll find some you'll like too... (the 'mp3' links prompt automatic downloads)

The rapidly changing climate system: Michael Oppenheimer, "a lead author with the Nobel Prize-winning Intergovernmental Panel on Climate Change gives a global warming overview". mp3 (34min).

The neuroscience of fair play: Donald Pfaff, "the head of the Laboratory of Neurobiology and Behavior at Rockefeller University describes how ethics may be a hardwired function of the human brain". mp3 (42min)

A slippery slope: Facts, ethics, and policy guiding neuroscience today: "Neuroscientist Michael Gazzaniga & lawyer Hank Greely debated the implications of neuroimaging, cognitive enhancers, stem cell research, improved medical diagnostic methods, and more in an animated conversation with journalist William Safire". mp3 (51min)

Ethics in the age of neuroscience: Michael Gazzaniga & bestselling author Tom Wolfe "discussed how knowledge of the brain can shed light on controversial issues and, perhaps surprisingly, bolster moral responsibility. mp3 (58min)

Resolving evolution's greatest paradox (Marc Kirschner): "Darvin's theory of natural selection has never been very good at explaining novelty or complexity in living organisms. The new theory of "facilitated variation", however, promises to fill in the gaps". mp3 (44min)

Is sustainable development feasible? "Director of the Earth Institute Jeffrey Sachs explained in his 2005 bestseller, "The end of poverty," how sustainable development could be feasible. But, he tells S&C, it will only be possible if key actors commit to some significant changes". mp3 (25min)

Sex, Drugs & DNA - Science's taboos confronted: "S&C speaks with scientist-turned-policy wonk Michael Stebbins about his new book, which takes the Bush administration to task for policies that Stebbins says mislead the public and are bad for science and scientists." mp3 (22min)

How to be happy - a geneticist-turned-monk takes a scientific approach to a spritual life: "Matthieu Ricard was a geneticist at Institut Pasteur before becoming a Buddhist monk. He spoke at the New York State Psychiatric Institute about his new book, "Happiness: A Guide to Developing Life's Most Important Skill", and about research published in PNAS in 2004 suggesting that meditation can induce long-term neural changes". mp3 (59min)

Mind vs Soul - a Philoctetes centre roundtable: "Six scholars of psychology, neuroscience, and religion discuss the relationship between the brain, the mind, emotional consciousness, and the possibility of a higher functioning that might be called soul." mp3 (1:31h)

Genomics & minorities: "While many biologists view genomics as an unmitigated boon, social scientists remain wary of its potential for misuse. NYU sociologist Troy Duster discusses how some old concepts of race are quietly creeping back into genetics, with disturbing implications for medicine and forensics." mp3 (19min)

Coming to life: How genes drive development: "S&C speaks with Nobel Laureate Christiane Nüsslein-Volhard about her book "Coming to life", in which she chronicles the astonishing progress scientists have made in understanding how genes drive the development of cells", as well as about some of the problems faced by women in science and how these could be solved. In the end I was just dissappointed to hear that she doesn't have kids of her own, which seems to be part of the women in science problematic. mp3 (21min)

Making of the fittest: "Geneticist Sean Carroll elucidates how DNA can provide a record of evolution by so-called "fossilized genes." In a lecture at the American Museum of Natural History, he explains how DNA can reveal expressed traits that have been lost, gained, and modified throughout time." mp3 (43min)

Paths to recovery in major depression: insights from functional neuroimaging: "Helen Mayberg presents her conceptualization of the functional brain networks underlying depression and discusses how a variety of therapeutic modalities, including meditation and cognitive behavioral therapy, may play a role in treatment and maintaining remission from depression". m4b (54min, enhanced podcast (viewing instructions))

Moral minds: "Harvard professor Marc Hauser says a radical rethinking about our ideas on morality is long overdue. He argues that the human brain evolved an inherent ethical instinct that forms the basis of our moral systems". mp3 (55min)

Shaping the future: "Commemorating the 50th anniversary of New Scientist magazine, E.O. Wilson, Sherry Turkle, and Paul Davies considered our changing relationships with science and technology that will shape the" world of tomorrow. I found Turkle's talk about our (present & future) relationships with technology, especially the internet and increasingly also robots, and how these could change our relationships with people since they provide "the illusion of companionship without the demands of friendship" particularly thoughtprovoking. mp3 (1:15h)

Mystery of the mind - what is consciousness? "Renowned NYU neuroscientist Joseph LeDoux joins a psychologist, a philosopher, an author, and a psychotherapist to debate and define the meaning of consciousness". mp3 (1:27h)

Neanderthal brains: "Bruce Lahn, whose lab in the Human Genetics Department at the Uni of Chicago researches human brain evolution, explains the genetic link he has discovered between homo sapiens and neanderthals". mp3 (20min)

Urban sustainability: Albert Appleton, a senior fellow at the CUNY Institute for Urban Systems and former Director of the NYC Water & Sewer System discusses some principles of sustainability and presents a regional perspective on biodiversity. mp3 (33min)

Medical Apartheid: Harriet Washington, "a NY science journalist, who has written the first full history of the shocking mistreatment that black Americans have suffered as unwilling and unwitting experimental subjects", discusses her research. Very disturbing. mp3 (30min)

I, WOZ: "Steve Wozniak, cofounder and inventor of Apple computers, describes his childhood, his sources of inspiration, and the offbeat thinking that led to the Apple II computer". mp3 (56min)

From animal to person: "Daniel Dennett, philosopher and codirector of the Center for Cognitive Studies at Tufts Uni, describes the evolution of human culture, which he says is a "second information highway," swifter and more reliable than genetic transmission". mp3 (34min)

The science of happiness: The popular spanish science journalist and television host Eduardo Punset offers insights and a formula from his book, "The happiness trip: a scientific journey," a bestseller in Spain and newly released in the USA". mp3 (37min)

The stuff of thought: "Hear what Harvard University psychologist Steven Pinker has to say about language and cognition, what swearing reveals about emotion, and what innuendo says about relationships". mp3 (1:03h)

The mind and music: "Physician, neurologist, and author Oliver Sacks speaks about his book, Musicophilia: Tales of Music and the Mind". mp3 (43min)

Daydreaming and night-dreaming: John Antrobus, Eric Klinger, Malia Mason, Ethel Person, and Jerome Singer discuss "stimulus-independent thought, including review of data from neuroscience imaging and clinical applications of research on human fantasy". mp3 (39min)

Climate change - Coral reefs, glacial lakes, and forest canopies: Oceanographer Richard Feely, geochemist W. Berry Lyons, and biologist Margaret Lowman discuss factors that govern the process of climate change based on their field research. mp3 (55min)

The origin of brain degenerative disorders: Patrick Hof, "a Mt. Sinai School of Medicine neuroscientist explains the morpho-molecular features that render certain neuronal populations of the brain vulnerable to degeneration". mp3 (1:05h)

This collection is far from extensive and subjective to boot, so I suggest you check out the other podcasts for yourself.

(yes, obviously sex & the city has nothing to do with these podcasts - i just wanted an excuse to put up a pic of the four women that propagate stupid female stereotypes and are even proclaimed heroes by their sheepish followers in return, but make me absolutely sick...)

some news on depression

2008-06-13T23:42:00.000+01:00

I tried to make sense of the depression-related abstracts I've accumulated over the past few months by briefly summarising them in little packets according to sub-topic. So here the's result, little tidbits from psychology, neuroimaging and systems neurobiology over biochemical signalling and serotonin transporter polymorphisms up to the immune system and inflammation... Might try to do the same with anti-depressant papers in the near future if time permits.

Risk factors for depression apparently include being female, non-white American, smoking, drinking or doing other drugs, being of lower socioeconomic status, and engaging in delinquent behaviour, while protective factors include 2-parent family structures and a good connection to parents, peers and school as well as high self-esteem. No shit, Sherlock.. (Costello et al, 2008. J Consult & Clin Psych). A family atmosphere characterized by expressed emotion (shouting?) and perceived criticism might be a risk factor in developing depression in later life, however, these factors do not seem to contribute significantly to relapse (Kronmüller et al, 2008. Psychiat Res).

Neuroimaging of depression points to hyperactivity of limbic structures that are involved in experiencing and expressing emotion, which weakens the ability of dorsal cortical structures that normally regulate affect to influence said limbic areas (Gotlib & Hamilton, 2008, Curr Dir Psychol Sci, free full access). Depressed individuals might give biased attention to negative emotional stimuli, and in addition, someone who is depressed might be more likely to perceive neutral stimuli (such as facial expressions) as negative, when compared to healthy invidiuals (Gollan et al, 2008. Psychiat Res).

Amygdala volumes in unmedicated depressed subjects tend to be smaller than controls, while antidepressant medication appears to result in increased amygdala volumes (Hamilton et al, 2008. Mol Psychiat, metastudy). The association of hippocampal volume and different depression subtypes (eg atypical, melancholic) remains uncertain (Greenberg et al, 2008. Psychiat Res).

Different calcium-sensitive adenylyl cyclase isoforms expressed in limbic areas differentially influence pro/anti-depressive behaviour and neurotrophic signalling but not hippocampal cell proliferation in KO mice (Krishnan et al, 2008. Biol Psychiat). In depression (or at least in the brains of clinically depressed individuals who successfully committed suicide), Gs may be localised to lipid rafts where it is less likely to coupleto adenylyl cyclase. Antidepressants may upregulateGs signaling to adenylyl cyclase via changes in membrane composition (Donati et al, 2008. J Neurosci).

Increased plasma levels of vasopressin, a nonapeptide involved in the neural and endocrine response to stress and expressed in the hypothalamus, pituitary and in limbic regions, are linked to affective disorders such as anxiety and depression. In addition, a single nucleotide polymorphism (SNP) of the vasopressin 1b receptor is associated with a decreased risk of depression (Surget & Belzung, 2008. Eur J Pharm, review).

Serotonin transporter gene haplotypes may be associated with the effect of threatening life events on development of a depressive phenotype after all (Lazary et al, 2008. Biol Psychiat). Likewise, SNPs in the serotonin transporter gene may be associated with suicide attempts, which argueable could constitute a symptom of depression (though not all suicide attempters need be clinically depressed) (Bah et al, 2008. Psychiat Res). Transgenic mice, with reduced or lacking serotonin transporter functionality, display a wide variety of phenotypic changes - from an increase in anxious behaviours (and probably also signs of depression) to changes in gut mobility. Although findings in human genetic-association studies and the likes are not as robust, many phenotypic changes observed are similar to those found in rodents (Murphy & Lesch, 2008. Nat Rev Neurosci, review). Serotonin transporter inhibition has differential effects, depending on whether it went missing early in development via knock-out, or inhibited pharmacologically later on in life. While the former increases the risk of depression in adulthood, the latter inhibits it. 30 genes appear to be expressed differentially when comparing KOs to pharmacologically treated animals, and several transcription factors involved in survival, proliferation and migration of serotonergic neurons during development seem to be involved (Ichikawa et al, 2008. Biochem & Biophys Res Comm). Similarly, neonatal exposure of female mice to escitalopram results in those mice showing signsof depression in the form of sleep anomalies, anhedonia, increasedhelplessness etc, while escitalopram did not have these effects in adult mice (Popa et al, 2008. J Neurosci).

The RNA expression of CamKIIa, tyrosine hydroxylase, CART, Homer1, glutamate decarboxylase and a number of other genes is downregulated in the frontal cortex following the exposure of rats to chronic mild stress (which may reflect the (pre-)depressed state in humans). Some of the genes have already been implicated in affective disorders and anhedonia in other studies (Orsetti et al, 2008. Eur J Neurosci).

Depressed female outpatients who suffered physical neglect during childhood display decreased plasma BDNF levels and worse performance in verbal recall tests than depressed and non-depressed individuals (Grassi-Oliveira et al, 2008. Biol Psychiat). 13 variants in the neurotrophin receptor kinase 3 gene may be somewhat associated with early-onset major depressive disorder (Verma et al, 2008. Biol Psychiat).

As if depression, loneliness, stress and grief weren't bad enough on their own, these factors can also increase ones risk of having a heart attack (substracting for smoking, poor sleep and other such things). Proinflammatory cytokines seem to be to blame. Au contraire, laughter, happiness and self-esteem lower the expression of some cytokines (Coombs, 2008. Nat Med, news article). Vice versa, increased immune activity due to (chronic) illness could lead to the development of depression in vulnerable individuals (Dantzer et al, 2008. Nat Rev Neurosci, review). SNPs in several genes critical for T-cell function are significantly associated with major depressive disorder in Mexican Americans, further underscoring the putative interplay of the immune system and depression (Wong et al, 2008. Mol Psychiat). Tumor necrosis factor (TNF) beta and soluble TNF receptor plasma levels are elevated in acutely depressed Bavarians (Himmerich et al, 2008. Eur Psychiat).

free fall

2008-06-12T13:45:00.002+01:00

these days i like to sit next to my friend, the fig tree. it's gotten so big, who would've thought? but i saw the fig leaves grow every day from the point where they were as small as a cent coin up to now when every leaf could easily cover the mightiest of adams. is the fig tree looking at the stars? i'm not. i guess i'm a bit planetist in that respect; besides, my eyes have always been weak, so i can never see all the stars anyway, only the 'bright' ones. no, i sit and look at our house, the lights, the other plants around me. i sit and i smoke. it's one of those rare moments, in which the constant stream of thoughts goes silent. sometimes the wind tries to talk to me, using the fig tree as an interface. but i don't understand the wind anymore, instead i can find meaning in techno tracks. my parents don't understand my affinity for the internet. maybe i won't understand my children's affinity for humanoid robots? maybe they will come to me one day and ask: 'mum, i've been thinking about getting an implant...' i guess if i'll have done things right as a mother they might actually do so. i'm using my siblings as guinea pigs. i try to be open with them in an attempt to get some trust in return... so, do they tell me everything? hell no. will they tell me the important things? i hope so. i'm not big on asking questions. the fig tree isn't big on talking at all, which is fine. we just sit. my friend would have never grown so big in north-west germany if it wasn't for global warming. i'm getting scared of climate change, maybe it's too late for that - well, there's always bill hicks to fall back on. maybe there's someone out there by the stars doing a better job than us down here.

parkinson's disease papers

2008-06-11T22:19:00.001+01:00

crazyness: the guys at neuroinformation.org have compiled lists of reviews from 2004 - 2008 for PD, alzheimer's and multiple sclerosis as well as reviews from 2000 - 2008 on essential acids eg omega-3.

here's a collection of PD papers that i came across lately (most are from 2008), and i tried to cover a broad range of topics. there's so much out there, but i think it could be useful to keep up to date with what's happening around one's subfield of interest, even if it's just by getting a glimpse of the research that's being done...

dopamine (DA)

merims & giladi: DA dysregulation syndrome, addiction and behavioural changes in PD. +++
cropley et al: pre- and post-synaptic DA imaging and its relation to with frontostriatal cognitive function in PD: PET studies with [¹¹C]NNC 112 and [¹⁸F]FDOPA. +
panzacchi et al: a voxel-based PET study of DA transporters in PD - relevance of age at onset. +++
caudle et al: altered vesicular DA storage in PD - a premature demise. (review) +++
mallet et al: disrupted DA transmission and the emergence of exaggaterated beta oscillations in subthalamic nucleus and cerebral cortex. +
mastroeni et al: microglial responses to DA in a cell culture model of PD. ++

non-motor symptoms

kummer et al: frequency of psychiatric disorders in young-onset PD does not differ from typical late-onset PD. ++
bouchard et al: age- and dementia-associated atrophy predominates in the hippocampal head and amygdala in PD. +
parnetti et al: cerebrospinal fluid biomarkers in PD with dementia and dementia with lewy bodies. ++
cheon et al: nonmotor symptoms in PD - prevalence and awareness of patients and families. ++

non-genetic factors contributing to PD

hatcher et al: PD and pesticides - a toxicological perspective. (review) +++
smith et al: stress accelerated neural degeneration and exaggerates motor symptoms in a rat model of PD. +++

treatments: L-dopa etc

fraraccio et al: absence of cognitive deficits following deep brain stimulation of the subthalamic nucleus for the treatment of PD. ++
samadi et al: mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. ++
lee et al: kynurenic acid attenuated MPP+-induced DAergic neuronal cell death via a Bax-mediated mitochondrial pathway. ++
hirano et al: dissociation of metabolic and neurovascular responses to L-dopa in the treatment of PD. +
sebastianelli et al: the L-amino acid carrier inhibitor BCH reduces L-dopa-elicited responses in DAergic neurons of the SNc. ++
locke et al: acetaminophen (paracetamol) attenuates DA neuron degeneration in animal models of PD. ++
wright et al: microglial activation is not prevented by tacrolimus but DA neuron damage is reduced in a rat model of PD progression. ++
armentero et al: dietary restriction does not prevent nigrostriatal degeneration 6-hydroxydopamine model of PD. +

(stem) cell transplants

kordower et al: lewy body-like pathology in long-term embryonic nigral transplants in PD. +++
li et al: lewy-bodies in grafted neurons in subjects with PD suggest host-to-graft disease propagation. +++
mendez et al: DA neurons implanted into people with PD survive without pathology for 14 years. ++
loturco & kriegstein: manipulating midbrain stem cell self-renewal. (preview) ++
svendsden: stem cells and PD - towards a treatment, not a cure. (preview) +

genetics and PD

bergmann et al: PITX3 polymorphism is associated with early-onset PD. ++
tan & skipper: pathogenic mutations in PD. (review) +++
dodson & guo: pink1, parkin, DJ1 and mitochondrial dysfunction in PD. (review) +++
kroemer & blomgren: mitochondrial cell death control in familial PD. (free access primer) +++
sironi et al: parkin analysis in early onset PD. +
bardien et al: molecular analysis of the parkin gene in south african patients diagnosed with PD. ++

alpha-synuclein

gallardo et al: a molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and beta-amyloid peptides. ++
crews et al: alpha-synuclein alters notch-1 expression and neurogenesis in mouse embryonic stem cells and in the hippocampus of transgenic mice. +++
shavali et al: mitochondrial localization of alpha-synuclein overexpressing cells. +++
sandal et al: conformational equilibria in monomeric alpha-synuclein at the single-molecule level. (free access) ++
hoepken et al: parkinson patient fibroblasts show increased alpha-synuclein expression. +++
thirunavukkuarasu et al: multiparametric fluorescence detection of early stages in the amyloid protein aggregation of pyrene-labeled alpha-synuclein. ++

cell bio & electrophysiology

alvira et al: activation of the calpain/cdk5/p25 pathway in the girus cinguli in PD. ++
greffard et al: a stable proportion of lewy body bearing neurons in the substantia nigra suggests a model in which the lewy body causes neuronal death. +
strauss et al: increasing extracellular potassium results in subthalamic neuron activity resembling that seen in a 6-hydroxydopamine lesion. +++

to answer your question...

2008-06-10T22:54:00.005+01:00

on how the floating about of molecules and attachment seen in the clip (ht: scienceroll) works:

- Shulman-Peleg et al (2008) Prediction of Interacting Single-Stranded RNA Bases by Protein-Binding Patterns. J Mol Bio 379: 299-316.

...well, okay - so this actually doesn't answer the question at all. but at least it's not improbable that we do know how the amino acid finds its right spot on the ribosome, if we can predict which proteins will bind to a given RNA fragment, no?

;)

ada byron (1815-1852)

2008-06-05T12:56:00.006+01:00

wired published an article about ada - the countess of lovelace - byron, who 'wrote the first computer program' after having come in contact with charles babbage, who thought up the first computer:

"1833: Ada Byron meets Charles Babbage. He designed an early computer, and she would write the first computer program.

Ada's father was the poet Lord Byron, but her parents separated when she was a month old. Her famous -- and poetically wild -- father went to Greece, and she never knew him.

Ada was 15 when she met the Cambridge mathematics professor Babbage 175 years ago today. Babbage had already received funding from Parliament to build a "difference engine" that could do mathematical calculations. While that project was still unfinished, he conceived in 1834 a new and broader idea: an "analytical engine" that "could not only foresee but could act on that foresight."

In 1835, Ada married William King, who inherited the title Earl of Lovelace in 1838, making her Countess of Lovelace. They had three children, but Ada's family and social responsibilities did not keep her from continuing her study of advanced mathematics.

Babbage, meanwhile, gave a seminar on the analytic engine in Turin, Italy, in 1841. Countess Ada translated the article about the presentation and showed it to Babbage. He was apparently better at conceiving things than explaining them (unheard of in a mathematician, eh?) and suggested that Ada expand the article with her own notes.

When published in 1843, those notes ran three times as long as the original article. Ada predicted that a computing machine could compose music, draw graphics and find application, so to speak, in business and science.

She also wrote a plan for the analytical engine to calculate Bernoulli numbers. It's now considered the first computer program. The countess originated the idea of a loop in a program, which she likened to a "snake biting its tail."

Ada was also a friend to novelist Charles Dickens, scientist Michael Faraday, inventor Charles Wheatstone and David Brewster, creator of the kaleidoscope. She was an opium addict who had numerous affairs and gambled away a lot of her family fortune. She died of cancer in 1852, two weeks shy of her 37th birthday.

The countess of Lovelace has attained recent fame through Betty Toole's 1992 edition of her correspondence, Ada, The Enchantress of Numbers and Lynn Hershman-Leeson's 1997 film Conceiving Ada, starring Tilda Swinton.

The U.S. Department of Defense named a computer language "Ada" in her honor."

very interesting, especially the links - and a great excuse to advertise my recent post about annemarie schwarzenbach.

yay for cool women!

the function of alpha-synuclein

2008-06-04T23:50:00.003+01:00

α-synuclein is expressed in several brain regions with varying intensity. Clayton and George (1998) point out that it is most commonly found in areas involved in some form of learning/adaptation and active synaptic plasticity. Solano et al (2000) showed mRNA expression of SNCA to be highest in the substantia nigra pars compacta (SNc) but other prominent regions include the pars reticulata, ventral tegmental area, deep layers of the neocortex, the hippocampus and entorhinal cortex, the basis pontis, the cerebellar granule cell layer and the locus cereuleus. α-synuclein is enriched in synaptosomes across different species and has been shown to transiently associate with presynaptic vesicles, especially the reserve/resting pool (Kahle et al, 2002; Cabin et al, 2002). Fortin et al (2004) also showed that localisation of alpha-synuclein to the synaptosome is mediated by lipid rafts. In addition, alpha-synuclein has been found to colocalise with the synaptic protein synapsin I (Withers et al, 1997). So what's it do?

Knock out mice lacking α-synuclein develop normally and show no gross morphological abnormalities. Apart from this observation - good for the mice but not so useful for us - the studies of alpha-synuclein KOs have been a bit inconsistent. Abeliovich et al, who performed the first KOs in 2000, observed that the neuronal/synaptic architecture of KO mice as well as synaptic pools looked normal, although there was a reduction of striatal DA by about 18%. In striatal brain slices, DA release and reuptake after single pulses or short trains (10 x 20Hz) wasn't altered. However, cells showed faster recovery of DA release after the 2nd pulse in a paired stimulus depression paradigm. This went in hand with an attenuated locomotor response to amphetamine. Hence Abeliovich et al suggested that alpha-synuclein might be involved in negative regulation of the readily releasable pool of DAergic synaptic vesicles. Fine, one might think. Got that kinda sorted..

Well, not so fast... Cabin et al came along in 2002, and by investigating the synaptic ultrastructure of alpha-synuclein lacking murine embryonic hippocampal cultured neurons, showed a 50% decrease in reserve pool vesicles as well as a 26% reduction in docked vesicles. Hippocampal synapses of 2-month old mice showed a 44% decrease in reserve pool vesicles, but no significant change in the number of readily releasable vesicles. These results went in line with earlier findings by Murphy et al (2000). However, some results failed to be replicated as no change was observed in quantitative immunoblot analysis of synaptosomes of WT and KO mice. There was no change in response to high frequency stimulation (HFS) (40 x 100 Hz) in the CA1 region of the hippocampus, which depletes the readily releasable pool of vesicles but doesn't affect the reserve/resting pool. However, Cabin et al suggest a much faster rate of vesicle depletion in KO mice based on EPSP declines after prolonged repetitive stimulation (PRS) (10Hz), also when the NMDA-component of the EPSP was removed. Higher frequency (30Hz) PRS increases Ca2+ concentration in nerve terminals, and at this frequency no more differences between WT & KO are observed while there is a difference at 14Hz PRS, unless Ca2+ concentration is high (5 mM). In addition, Cabin et al observed that KO mice were still getting high on amphetamine as if nothing ever happened. If anything, they showed a slightly anxious phenotype in certain tests (not while high). In conclusion it was suggested that alpha-synuclein may regulate the refilling of the readily releasable pool by controlling the size of the reserve/resting pool in the hippocampus. Hmm.

Intuitively, it doesn't seem to make much sense for a stand-alone protein to have different (opposite..) functions in different brain areas, unless the function depends on interactions with other proteins which might be differentially expressed. So why does DA reuptake and release in the striatum seem influenced by alpha-synuclein while it has very different effects in the hippocampus? A number of studies suggest a role for α-synuclein in DA biosynthesis, recruitment to vesicles and reuptake (reviewed in: Beyer 2006; Lotharius & Brundin 2002). Hence the effect observed by Abeliovich et al might have been observed due to some effect on DA biosynthesis, turnover etc. See:

Kuhn et al (2007): DA receptor signaling is down-regulated; cellular development, nervous system function, and cell death related genes are up-regulated, similarly altered in SNCA(-/-) and SNCG(-/-) mice. In addition, TGF-beta signaling and apoptosis pathways genes were significantly up-regulated in SNCA(-/-) mice but down-regulated in SNCG(-/-).

Drolet et al (2004): Attenuated loss of striatal DA after chronic MPTP exposure, no loss of vesicular monoamine transporter 2 (VMAT2), no change in DOPAC/DA ratio. Also, in 2006: catalytic activity of tyrosine hydroxylase is regulated by alpha-synuclein via a phosphorylation event.
Sidhu et al (2004): alpha-synuclein expression alters DAT-mediated uptake of synaptic DA.

Yavich et al (2004): alpha-synuclein is directly (that's always nice..) involved in DA recruitment and presynaptic DA compartmentalisation.

However, this not all. alpha-synuclein seems to be really multitalented...

Jenco et al (1997): alpha-synuclein inhibits phospholipase D, which may regulate monoaminergic vesicle content and nerve terminal DA storage.

Ostrerova et al (1999): since it shares structural homology to 14-3-3 proteins, α-synuclein could possibly also act as a molecular chaperone.

Ghee et al (2000): α-synuclein is thought to interact with the proteasome.

George et al (2008): reduced anxiety-like behaviour in A53T transgenic mice compared to WT and KOs.

Austin et al (2006): morphological differences, increased reactivity of microglia including elevated levels of proinflammatory cytokines, TNF-α and IL-6 upon stimulation, but impaired phagocytic ability.

et cetera perge perge..

Which leaves us with the conclusion that "to date, the exact function of alpha-synuclein remains elusive." Thank you.

PS: It goes without saying that the couple of studies cited here are only the tip of the iceberg. Google scholar comes up with 1090 papers with 'alpha-synuclein' in the title (even if not all of them deal with its 'normal' function.. it's still a lot..)

annemarie schwarzenbach (1908 - 1942)

2008-06-03T09:53:00.001+01:00

annemarie schwarzenbach was born into a rich industrial family just outside zürich in 1908. her androgynous style was fostered by her family from early on, perhaps not surprisingly given that her mother renée had openly had a lesbian affair with opera singer emmy krüger. other than that, schwarzenbach's relations with her family didn't seem to be the best, partially due to her strong anti-fascist views which were anything but shared by her family (her grandfather swiss general ulrich wille openly embraced third reich contemporaries). one of annemarie's suicide attempts is thought to have resulted from disagreements with her family, and the schwarzenbach clan, in particular annemarie's grandmother burned a lot of annemarie's diaries and personal correspondence after her death.

schwarzenbach studied in zürich as well as in paris, already publishing several literary works during her studies and earning her doctorate in history at the young age of 23. schwarzenbach went to berlin after her studies, where she got hooked on morphine, and became friends with klaus and erika mann, thomas mann's progeny. annemarie was open about her homosexuality and had many love affairs with intelligent and influental women throughout her lifetime, including a liason with erika.

around 1933, schwarzenbach began to travel a lot; she visited spain with the photographer marianne breslauer, traveled to persia (now iran) and moskau before returning to switzerland in 1934. annemarie returned to persia in '35, and married her friend claude clarac, a french diplomat based in persia (iran). this marriage was purely platonic however, as clarac was gay himself, and produced no offspring other than a diplomatic passport for schwarzenbach. after the wedding, schwarzenbach was struck by a depressive episode, neither the first nor last in her life, which was worsened by a scandal over her affair with a turkish ambassador's daughter. schwarzenbach continued travels after going to rehab in '39, visiting afghanistan and then moving to new york. in the usa, schwarzenbach teamed up with barbara hamilton-wright, traveling across america and writing about race and class relations for the european press. annemarie returned to switzerland after a trip to belgian congo in 1942.

schwarzenbach's journalism was inspired by her travels, while her prose provided insight into her ongoing loneliness and mental crises. she was known to produce excellent literary works in an almost manic fashion whenever she wasn't being held down by her ongoing struggles with depression, morphine addiction and alcohol abuse. schwarzenbach's works are said to be a hybrid of autobiography and fiction, as well as cultural/political commentaries accompanied by photos (eg on the rise of fascism in eastern europe, the hitler youth, or traditional life in central asia. however, most of her works have been translated into french instead of english and weren't published until after her death. particularly in the 1980's, memories of schwarzenbach were revived by a whole host of biographical works and annotated editions of her work mainly by german scholars and feminists, highlighting that she had been one of the most important travel/photojournalists of the 20th century.

it would have been annemarie schwarzenbach's putative 100th birthday about a week ago, had she not died from a head injury, inflicted by a cycling accident at the age of 34. what a banal ending to an intense and inspiring life...

sources/further reading:
wikipedia (german)
swiss institute exhibitions
schwarzenbach @ the GLBTQ
an account of schwarzenbach's life by martin uebelhart (german)

dr. jekyll

2008-06-02T18:57:00.002+01:00

(ayoe angelica)

the structure of 'normal' alpha-synuclein

2008-06-02T07:44:00.005+01:00

α-synuclein, a small highly conserved 19kD protein that has been implicated in a number of neurodegenerative diseases, belongs to a protein family including β- and γ-synuclein, first identified in the electric organ of Torpedo californica, as well as in bovine and songbird brains (Clayton & George 1998).
The α-synuclein gene SNCA has been assigned to chromosome 4q21 and consists of six exons, five of which are transcribed (Spillantini et al, 1995). SNCA is subject to alternative splicing, producing three α-synuclein isoforms, of which the 140 amino acid version is the most prominent. In addition, α-synuclein undergoes extensive posttranslational modifications such as phosphorylation, which are thought partially responsible for aggregation in synucleinopathies (Beyer 2006).

The primary sequence of α-synuclein consists of three regions: the amino-terminal repeat region comprises seven imperfectly conserved 11-residue repeats (Beyer 2006), and is implicated in α-synuclein’s ability to bind to phospholipid membranes (eg synaptic vesicles) upon adopting an amphipathic α-helical structure (Davidson et al, 1998). The non-amyloid component (NAC) domain in the middle of the protein is hydrophobic, and critical to α-synuclein’s propensity to aggregate, while the carboxy-terminal domain is acidic, highly flexible and always remains unstructured (Eliezer et al, 2001). α-synuclein is natively unfolded in the cytosol, and only adopts a secondary structure upon membrane binding or during malicious aggregation into beta-sheet containing oligomers, and (proto)fibrils (as seen in Lewy bodies in Parkinson’s Disease) (Lee & Trojanowski 2006; Spillantini et al, 1997). More on alpha-synuclein's ability to aggregate (and the mutations that seem to foster aggregation) at some other point...

weekend links IX

2008-05-31T08:01:00.005+01:00

electroconvulsive therapy 2.0 has been in the news this week, and sounds rather promising. in a similar vein, i really enjoyed sherwin nuland's TED talk on his experience with depression and old-fashioned ECT back in the 70s.

john horgan wrote a sensible and amusingly snarky piece on "brain chips and other dreams of the cyber-evangelists" in the chronicle of higher education, 2005 (huge ht:neuroanthropology).

also thanks to neuroanthropology: the rockefeller university brings you its recent symposium on evolution "from RNA to humans" in the form of 19 videos. i haven't watched them yet, but expect them to be more educational than your usual 'sciencey' videos at youtube.

andrea gaggioli from positive technology journal points to a series of lectures by alan wallace to take place in june, about psychological/neuroscientific studies of meditation. sure sounds interesting, i hope the lectures will be online.. the lectures will be presented by PERCRO, a perceptional robotics lab based in pisa; their projects look really exciting too.

something not quite as cool is the recent news on wired and cnn about a semi-autonomous armed iRobot. makes me sick to my stomach to the point of not actually wanting to know more about developments in warfare.. but i guess those 1204 billion US dollars (as of 2006) that are being spent by the military each year worldwide have to go somewhere... :(

the vatican wants to excommunicate female priests and bishops who try to ordain them. i can imagine that for someone whose faith is strong enough to want to become a priest, exommunication is a pretty big deal. gotta love the roman catholic church and its sexism..

interesting series of photos from richard ross' new book "architecture of authority". the wired gallery features mostly prisons, but in the book features all sorts of institutional buildings from schools over mosques and churches up to guantanamo bay and the likes.

new findings from the CALERIE study suggest that humans on a caloric restriction diet don't suffer from an increase in depression/anxiety as rodents seem to do. break-down at ouroboros.

well, and then there's obviously the feeding robot/monkey and phoenix (yes, it's a twitter feed - an admittedly very cool use of the big T..) but you already know that..

7th annual hardcore wine tasting

2008-05-29T09:10:00.001+01:00

... fresh interesting alcohol(ism) related abstracts -

acute alcohol consumption

filbey et al: exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry. ++
marple-horvat et al: alcohol badly affects eye movements linked to steering, providing for automatic in-car detection of drink driving. +++
kash et al: alcohol inhibits NR2B-containing NMDA receptors in the ventral bed nucleus of the stria terminalis. +++
fujii et al: acute and chronic ethanol exposure differentially affects induction of hippocampal LTP. ++
barrett et al: the role of dopamine in alcohol self-administration in humans - individual differences. +

alcoholism

nat rev neurosci research highlight: damping down alcohol dependance. +++
makris et al: decreased volume of the brain reward system in alcoholism. +++
hansson et al: neuroplasticity in brain reward circuitry following a history of ethanol dependance. +++
pandey et al: brain chromatin remodeling - a novel mechanism of alcoholism. +++
enoch: the role of GABA-A receptors in the development of alcoholism. (review) +++
walker & koob: pharmacological evidence for a motivational role of kappa-opiod systems in ethanol dependance. ++
wilhem et al: apolipoprotein E polymorphism, homocysteine serum levels and hippocampal volumes in patients with alcoholism - an investigation of a gene-environment interaction. ++

miscellaneous

ziolkowska et al: alpha-synuclein expression in the brain and blood during abstinence from chronic alcohol drinking in mice. ++
greene & grahame: ethanol drinking in rodents - is free-choice drinking related to the reinforcing effects of ethanol? (review) +
lardeux & baunez: alcohol preference influences the subthalamic nucleus control on motivation for alcohol in rats. ++
pan et al: increased leptin permeation across the blood-brain barrier after chronic alcohol ingestion. +++
robles & sabria: effects of moderate chronic ethanol consumption on hippocampal nicotinic receptors and associative learning. +++
roberto et al: cellular and behavioural interactions of gabapentin with alcohol dependance. +++

good ol'abstracts again II

2008-05-27T19:30:00.003+01:00

mooore aging-related articles, bunch of different topics..

mild cognitive impairment (MCI) & alzheimer's disease (AD)

dannhauser et al: an fMRI study of verbal episodic memory encoding in amnestic MCI. (free access) +
grabowski: more to MCI than meets the eye. (free access; review) +++
salat et al: white matter pathology isolates the hippocampal formation in AD. +
taddei et al: novel phage peptides attenuate beta amyloid-42 catalysed H2O2 production and associated neurotoxicity. ++
moloney et al: defects in IGF-1 receptor, insulin receptor and IRS1/2 in AD indicate possible resistance to IGF-1 and insulin signalling. +

neurotoxicity & neurodegeneration

outeiro et al: therapeutic role of sirtuins in neurodegenerative disease. +++
yang et al: mitochondrial DNA damage and repair in neurodegenerative disorders. +++
pérez-de la cruz et al: cytoplasmic calcium mediates oxidative damage in an excitotoxic/energetic deficit synergic model in rats. +
gonzalez et al: CITED2 signals through peroxisome proliferator-activator receptor-gamma to regulate death of cortical neurons after DNA damage. ++

neuroprotection & neurogenesis

fu et al: mecamylamine prevents neuronal apoptosis induced by glutamate and low K+ via differential anticholinergic-independent mechanisms. +
leng et al: synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons - roles of glycogen synthase kinase-3 inhibition. +++
prozorovski et al: Sirt1 contributes critically to the redox-dependent fate of neural progenitors. (corresponding nature research highlight) ++
dirnagl & meisel: endogenous neuroprotection - mitochondria as gateways to cerebral preconditioning? (review) ++

geriatric psychology

mast et al: vascular disease and future risk of depressive symptomatology in older adults - findings from health, aging and body composition. ++
brassen et al: ventromedial prefrontal cortex processing during emotional evaluation in late-life depression - a longitudinal fMRI study. ++
wise, contented, old people @ the thinking meat project. +++

general aging

tavernarakis: aging and the regulation of protein synthesis: a balancing act? ++
norris et al: hippocampal 'zipper' slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca2+ channels with aging. ++
wilson et al: reproductive hormones regulate the selective permeability of the blood-brain barrier. +++

when a woman loves a man.

2008-05-27T09:33:00.004+01:00

"When she says 'Margarita' she means 'Daiquiri'.
When she says 'quixotic' she means 'mercurial'.
And when she says, 'I'll never speak to you again,'
she means, 'Put your arms around me from behind as I stand disconsolate at the window.'

He's supposed to know that.

When a man loves a woman he is in New York and she is in Virginia
or he is in Boston, writing, and she is in New York, reading,
or she is wearing a sweater and sunglasses in Balboa Park and he
is raking leaves in Ithaca
or he is driving to East Hampton and she is standing disconsolate
at the window overlooking the bay
where a regatta of many-colored sails is going on
while he is stuck in traffic on the Long Island Expressway.

When a woman loves a man it is one-ten in the morning,
she is asleep he is watching the ball scores and eating pretzels
drinking lemonade
and two hours later he wakes up and staggers into bed
where she remains asleep and very warm.

When she says tomorrow she means in three or four weeks.
When she says, 'We're talking about me now,'
he stops talking. Her best friend comes over and says,
'Did somebody die ?'

When a woman loves a man, they have gone
to swim naked in the stream
on a glorious July day
with the sound of the waterfall like a chuckle
of water ruching over smooth rocks,
and there is nothing alien in the universe.

Ripe apples fall about them.
What else can they do but eat ?

When he says, 'Ours is a transitional era.'
'That's very original of you,' she replies,
dry as the Martini he is sipping.

They fight all the time
It's fun
What do I owe you ?
Let's start with an apology
Ok, I'm sorry, you dickhead.
A sign is held up saying 'Laughter'.
It's a silent picture.
'I've been fucked without a kiss,' she says,
'and you can quote me on that,'
which sounds great in an English accent.

One year they broke up seven times and threatened to do it
another nine times.

When a woman loves a man, she wants him to meet her at the
airport in a foreign country with a jeep.
When a man loves a woman he's there. He doesn't complain that
she's two hours late
and there's nothing in the refrigerator.

When a woman loves a man, she wants to stay awake.
She's like a child crying
at nightfall because she didn't want the day to end.

When a man loves a woman, he watches her sleep, thinking:
as midnight to the moon is sleep to the beloved.
A thousand fireflies wink at him.
The frogs sound like the string section
of the orchestra warming up.
The stars dangle down like earrings the shape of grapes."

_{- David Lehman

(shamelessly stolen from jumaxotl)}

über consciousness

2008-05-27T00:22:00.005+01:00

just as i think that philosophy should be a mandatory subject at university (and my occassional scorn for it is mostly a sign of envy; and the other part is finding it utterly impractical in terms of the results this discipline produces these days), i think molecular biology/biochemistry should be mandatory as well.

i would lie if i said i enjoyed my biochemistry studies back in the day, but in retrospect i am SO glad i pulled through somehow. especially now with neuroscience added - a focus on molecular/biochemical neuroscience so to speak - i feel that it was one of the best things that happened in my life.

why? simply because the complexity of molecular processes going on in one's body/brain at any given second is more than astonishing. i wish more people would realise the beauty of it, and see how amazing it is that we experience this constant mixing and mingling and phosphorylating and trafficking and synthesising and degenerating on the small scale as 'living', of which consciousness is just the tip of the iceberg. even illness becomes almost understandable, because heck - our organisms are capable of doing so much stuff exactly right, it's like a massive orchestra performing - how can we blame a tiny fraction of our cells or tissues for occassionally playing out of tune?

one does not need a god to stand in awe.

google reader again and again

2008-05-26T23:52:00.003+01:00

meh. i saw a little button last weekend, that you could convert into a bookmark (similar to the citeUlike javascript business) and use it to save any random webpage you came across with a note, therefore effectively adding it to the encephalon external that is google reader. but now i can't find it anymore...

do you know where it is or what it was called?

new blogs

2008-05-26T10:27:00.003+01:00

added a bunch of new blogs to the blogroll this morning:

90% true - now with 12% more truth.

a long way from eden -

brain blogger - topics from multidimensional biopsychosocial perspectives.

brain stimulant - blog covering several topics about the brain, neuroscience, neurotechnology and AI.

illusion sciences - why are we surprised by only some of the things that we see?

meteuphoric -

neuroscientifically challenged - making advances in neuroscience understandable to the beginning neuroscientist.

neurotopia V2.0 - stronger. faster. bloggier. now chock-full of glial goodness.

pharmaconutrition reviewed - putting science first.

physioprof - "step in, sit down, chill the fuck out"...

pink tentacle -

scienceroll - a medical student's journey inside genetics and medicine through web 2.0.

sharp brains - brain fitness, training & exercise guidance for individuals, companies and institutions.

the corpus callosum - is written by a psychiatrist at a small community hospital somewhere in midwestern USA.

the diaries of franz kafka, 1910 - 1923 - in progress (english and german).

the great beyond - the nature blog that rounds up science news from around the world.

understandingsociety - innovative thinking about social agency and structure in a global world.