Unraveling the Bacterial Rope Assembly Mystery

Ferran Garcia-Pichel and Martin Wojciechowski (Arizona State University) propose that the capacity to colonize unstable soil is the evolutionary advantage of bacterial assembly into ropes. This news feature was written on November 18, 2009....

Garcia-Pichel, F., & Wojciechowski, M. F. (2009) The Evolution of a Capacity to Build Supra-Cellular Ropes Enabled Filamentous Cyanobacteria to Colonize Highly Erodible Substrates. PLoS ONE, 4(11). DOI: 10.1371/journal.pone.0007801  The Evolution of a Capacity to Build Supra-Cellular Ropes Enabled Filamentous Cyanobacteria to Colonize Highly Erodible Substrates


See original: Research Blogging - All Topics - English Unraveling the Bacterial Rope Assembly Mystery

Ask a Nobel Laureate, John Mather on YouTube

Have you ever wanted to put your question directly to a Nobel Laureate? Now is your chance! NASA's John Mather, recipient of the 2006 Nobel Prize in Physics for measuring the echoes of the Big Bang, will answer a selection of your video questions on the NobelPrize YouTube channel.

See original: Nobelprize.org Ask a Nobel Laureate, John Mather on YouTube

Paradoxes of efficient market theory

Complex systems scientist Cosma Shalizi reviews economic journalist Justin Fox’s book The Myth of the Rational Market: A History of Risk, Reward, and Delusion on Wall Street for American Scientist magazine in the article Twilight of the Efficient Markets:
The Myth of the Rational Market, by Justin Fox, is an account—popular but thorough—of the roots, rise, [...]

See original: Resilience Science Paradoxes of efficient market theory

Motility of Cancer Cells

Cancer is a disease of multicellular organisms. In order to become multicellular, a certain amount of control needs to be exerted over each individual cell, cells can no longer move around, grow, and divide when they want too. Instead they must obey signals from the surrounding environment (including their fellow cells) which tell them what to do. Cancer, like anarchy, is what happens when the control breaks down, and individual cells start growing and dividing regardless.Uncontrolled growth leads to a neoplasm, a large mass of abnormal tissue. These can be benign, and merely exist in the body without causing too many problems, or they can start to become cancerous, invading surrounding tissues, and sometimes entering the bloodstream and spreading to further locations within the body.(Because of this, cancer is primarily a disease of deterministic multicellular organisms. Plants and other non-determinists can get tumours, but tend not to be so badly affected by them, as they are constantly growing anyway)In order to break away from the neoplasm and spread the disease cancer cells must gain motility. Studying how cancer cells move can be difficult in vivo because the conventional method of immuno-histology (which involves taking slices out of a tumour during development then fixing and staining them) prevent movement all together. Newer work has been done using Intravital imaging (shown diagrammatically on the rather cute little picture on the right) , where a fluorescently-labelled tumour is generated in an animal and then observed while the animal is anaesthetised. This gives a perfect in vivo image of what is actually happening inside the living tumour cell, in these images you can see cells moving in real time, and examine how they act under the effects of internal mutations and changes in external conditions.One of the things that this type of imaging revealed was that most of the cells in a tumour don't move (less than 0.1% tumour cells in vivo/hour). Furthermore, there were two types of movement. Firstly, individual cells, that darted around on their own, fairly quickly and in all directions. Secondly large clumps of cells, that moved relatively slowly, but in the same direction with a more ordered internal microtubular structure.Single celled movementTwo types of movement were first described; mesenchymal and amoeboid. As the main difference between them lies in the speed and number of direction changes it has been suggested that the distinction may be an artifact of different experimental conditions, rather than actual physical difference. The movement (which has been studied extensively in mesenchymal cells as they can be stuck down onto 2D surfaces) is initiated by signals to receptor tyrosine kinases. These turn on the small G-protein, Rac which, among other things, activates Arp2/3 proteins, which control the nucleation of actin subunits. In the diagram above the actin is shown in red, and it is used to generate movement of the cell. As the cell is forcing it's way through a thick external extracellular matrix (EMC) it also secretes proteases and MMPs to break this down, allowing easier forward movement.Collective cell movement(All images are taken from the reference below, and I've included the key for those with an interest in how eukaryote cells hold themselves together)Collective motility is the movement of whole groups of cells, either in clusters or chains. These cells can move between tissues, spreading the tumour (in particular they can get into the lymph system) but they are not normally found in the bloodstream. Interestingly, collective motility is seen when the conditions for single-cell motility have been blocked, suggesting that the rapid-moving single cells are a transient stage in order to get the tumour into the bloodstream. Once it finds a new environment, it reverts back to the less-motile stage, with large clumps of tissue still able to (very slowly) manoeuvre themselves into nearby tissues.---SAHAI, E. (2005). Mechanisms of cancer cell invasion Current Opinion in Genetics & Development, 15 (1), 87-96 DOI: 10.1016/j.gde.2004.12.002...

SAHAI, E. (2005) Mechanisms of cancer cell invasion. Current Opinion in Genetics , 15(1), 87-96. DOI: 10.1016/j.gde.2004.12.002  Mechanisms of cancer cell invasion


See original: Research Blogging - All Topics - English Motility of Cancer Cells

Duplicate publication guidelines from BMC

BioMed Central has developed useful guidelines for authors about exactly what is meant by duplicate (or redundant) publication. They cover not only  overlaps with  other journal articles but  issues such as preprint servers (and they mention the COPE  flowchart!).  You can find them at

http://www.biomedcentral.com/info/about/duplicatepublication

See original: Publication Ethics Blog Duplicate publication guidelines from BMC

One Pill Makes Your Libido Larger

It's every man's dream - a pill to make women want more sex. According to Boehringer Pharmaceuticals, that dream could be a reality in a few years, in the form of the strangely-named flibanserin. But is it the latest wonder-drug or just a glorified sleeping pill? Read on.

Flibanserin was originally developed as an antidepressant, but in clinical trials against depression it reportedly failed to perform better than placebo. The standard for getting approved as an antidepressant is low, so this is quite an achievement.

The BBC today described flibanserin as the "Female Viagra", which is rather confusing, because it's meant to increase sexual desire, which is one thing Viagra (sidenafil) doesn't do. The reason for the Female Viagra headline is that, as Professor John Thorp says:

"It's essentially a Viagra-like drug for women in that diminished desire or libido is the most common feminine sexual problem, like erectile dysfunction is in men"

Yes, one in ten women suffer apparently from "Hypoactive Sexual Desire Disorder" (HSDD) as Boehringer Pharmaceuticals helpfully informs us. And “As many as two out of every 10 women describe some degree of decreased sexual desire" according to Dr Charles de Wet, Boehringer medical director for the UK.

HSDD is a diagnosis in the DSM-IV, the American Psychiatric Association's listing of psychiatric illnesses, and it's been recognised as a disorder since 1980. It is not, however, a very popular diagnosis yet. There are only 60,000 Google hits for it, as opposed to 1,600,000 for "major depression" and, er, 90,000 for "neuroskeptic". Odd for a disorder apparently plaguing at least 10% of women.

Indeed, some people say that it's no more than a label invented by psychiatrists who didn't understand women and then promoted by drug companies in order to sell drugs. This is almost certainly true, but it's also a bit simplistic, because there are people who perceive themselves as suffering from low libido, and if flibanserin really helps them, that's surely a good thing.

How is flibanserin supposed to work? According to a paper on the Pharmacology of Flibanserin, it's a serotonin receptor 5HT1A agonist and a 5HT2A antagonist. This makes it a kind of cross between the antidepressants nefazadone and buspirone. Neither of these are widely used as antidepressants because they're not considered highly effective. Flibanserin is also a weak dopamine D4 receptor partial agonist. This might underlie its aphrodisiac properties, because drugs which increase dopamine levels are known to enhance motivation and libido (or indeed cause problematic hypersexuality.) In rats and mice, flibanserin has sedative effects and enhances the effects of other sedatives. It also has antidepressant-like effects in some tests but not all. Drug geeks can click the image on the left for more details.

*

Now for the big question - does it actually work? Well, there have been no published clinical trials yet. At all. The trials in depression, where it failed to work, have never been published. Hmm. However, four trials in "Hypoactive Sexual Desire Disorder" were recently completed and the results were presented yesterday at a sexual medicine conference in Europe (ESSM) in the form of three posters (1,2,3). The trials were known as - groan - VIOLET, ORCHID, DAISY and DAHLIA. I probably don't have to tell you that they were all funded by Boehringer Pharmaceuticals.

The main poster is Efficacy of flibanserin 100 mg qhs as a potential treatment for Hypoactive Sexual Desire Disorder in premenopausal women which pools the data from three trials with a total of about 1,400 women. They found that taking flibanserin 100 mg every night had small beneficial effects. Relative to placebo, it increased the number of "satisfying sexual encounters" by 0.7 per month. It also improved scores on questionnaire measures of sexual function, a bit.

In any trial like this you have to ask whether there is result cherry-picking going on. Maybe they asked dozens of questions about the women's sex lives, and they're only telling us about the minority where the drug seemed to work? People often do that but in this case, the Clinical Trials Register suggests there was no funny business of that kind. It also shows that there have been no trials using 100mg which weren't included in the poster, so the trials themselves weren't cherry picked either. That's reassuring. But it looks like the effects were only significant when all three trials were pooled - one poster shows the results of the ORCHID trial alone, and most were non-significant. 

What about the side effects? There's a whole poster about them. 100 mg nightly caused 14% of patients to drop out due to side effects, vs 7% of placebo - so 7% of people decided it wasn't worth it. It caused dizziness, nausea, fatigue, somnolence - and bizarrely, also insomnia. 50mg daily was much worse than 100 mg nightly, which suggests that taking this at night, rather than in the morning, is a good idea. But given what it is meant to treat, you'd want to do that anyway, right?

But this leads onto my biggest problem with this data. It's obvious from the side effects data that this drug is a sedative - it makes you tired and sleepy. The animal data show confirm this. It's much more likely to put you to sleep than it is to make you enjoy sex in any given month. Off the top of my head I suspect it's a sedative because it's a 5HT2A antagonist.

Any sedative can increase sexual desire as anyone who has ever been to a bar will know. So whether this drug actually has an aphrodisiac effect, as opposed to just being a sleeping pill, is anyone's guess. To find out, you'd need to compare it to a sleeping pill, say, Valium. Or a couple of glasses of wine. Until someone does that, we don't know if this drug is destined to be the next big thing or a big disappointment.

ResearchBlogging.org

Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S (2002). Pharmacology of flibanserin. CNS drug reviews, 8 (2), 117-42 PMID:...

Borsini F, Evans K, Jason K, Rohde F, Alexander B, & Pollentier S. (2002) Pharmacology of flibanserin. CNS drug reviews, 8(2), 117-42. PMID: 12177684   Pharmacology of flibanserin.


See original: Research Blogging - All Topics - English One Pill Makes Your Libido Larger

A New Look at Medical Errors in Residency Training

It’s a phenomenon that medical educators have long suspected but haven’t been able to prove: a rise in medical errors when newly-hatched physicians begin their residency training programs in July. This suspected occurrence has been studied several times, but until recently, no conclusive evidence existed that it actually was true. For the first time, a [...]...

Haller, G., Myles, P., Taffe, P., Perneger, T., & Wu, C. (2009) Rate of undesirable events at beginning of academic year: retrospective cohort study. BMJ, 339(oct13 1). DOI: 10.1136/bmj.b3974  Rate of undesirable events at beginning of academic year: retrospective cohort study


See original: Research Blogging - All Topics - English A New Look at Medical Errors in Residency Training

Droit, sciences polititiques, deux conférences d'Aldo Schiavone, EHESS, Paris, 18 et 25 nov 2009

18/11/2009 09:15
Europe/Paris

Aldo Schiavone,
directeur de Istituto Italiano di Scienze Umane,
professeur invité à l'EHESS,
tiendra les séminaires suivants :

L'égalité des anciens et des modernes
Mercredi 18 novembre à 17 h en salle 2 (105, Bd Raspail)

Légitimité et pouvoir : la justification de l'empire chez Cicéron
Mercredi 25 novembre à 17 h en salle 2 (105, Bd Raspail)

------------------------------
Ecole des hautes études en sciences sociales (EHESS)
Centre d'étude des normes juridiques - Yan Thomas

Le calendrier du centre
http://cenj.ehess.fr/

La liste de diffusion
http://cenj.ehess.fr/document.php?identifiant=listsympa

The impacts of wild horses on a desert ecosystem

...

Ostermann-Kelm, S., Atwill, E., Rubin, E., Hendrickson, L., & Boyce, W. (2009) Impacts of feral horses on a desert environment. BMC Ecology, 9(1), 22. DOI: 10.1186/1472-6785-9-22  Impacts of feral horses on a desert environment


See original: Research Blogging - All Topics - English The impacts of wild horses on a desert ecosystem

Internet against government corruption

Can the internet prevent government corruption? You’re probably never going to meet an entirely honest politician, but according to a statistical study by US researchers of 170 countries the internet could provide the tools necessary to reduce corruption significantly.

Martha García-Murillo of the School of Information Studies, at Syracuse University, New York, modeled political, economic and [...]Post from: David Bradley's Sciencetext Tech TalkInternet against government corruption...

Martha García-Murillo. (2010) The effect of internet access on government corruption. Electronic Government, An International Journal, 7(1), 22-40. info:/


See original: Research Blogging - All Topics - English Internet against government corruption

Shirley Wu: A brief analysis of commenting at BMC, PLoS, and BMJ

Shirley Wu
A brief analysis of commenting at BMC, PLoS, and BMJ - http://shirleywho.wordpress.com/2009...
Mr. Gunn, Mickey Kosloff, Greg Tyrelle and 6 other people liked this
Pretty plots. - Neil Saunders
I like the BMJ numbers. There is hope for more uptake of comments on papers. - Martin Fenner
I should note that the data for each publisher are not exactly comparable. For PLoS, I looked at articles with the all-time most comments (data courtesy of Pete Binfield). For BMC, I looked at the most highly accessed articles in the last 30 days (with a brief glance at the all-time list for a sanity check), though I also had a short list of all-time most commented articles (data courtesy of Euan Adie). For BMJ, I looked at all articles that had been commented on in the last 30 days. So for each, the context is different. That was mostly out of necessity - none of the publishers provide the same lists (e.g. a "most highly commented papers" list would have been great). So add that on top of the small sample sizes and it's even harder to draw any definitive conclusions. - Shirley Wu

See original: FriendFeed - search Shirley Wu: A brief analysis of commenting at BMC, PLoS, and BMJ