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  • July 24, 2010
  • 08:30 PM

Antigen presentation in the bloodstream: How invariant NKT cells are activated by Lyme disease spirochetes

by Microbe Fan in Spirochetes Unwound

The spirochete Borrelia burgdorferi is the tick-borne agent of Lyme disease, which affects the joints, nervous system, and heart.  After being deposited into the skin by an infected tick, the spirochete must enter the bloodstream so that it can circulate in the blood to gain access to its target organs.The host doesn't sit idly as B. burgdorferi establishes an infection.  Invariant natural killer (iNKT) cells are one of the tools deployed by the immune system in its battle against the Lyme spirochetes.  Scientists know this because B. burgdorferi-infected mice lacking iNKT cells ended up with more spirochetes in their tissues and greater joint swelling than mice with a complete immune system.2 iNKT cells are an odd type of T cell.  Like other T cells, iNKT cells have a T cell receptor (TCR), yet they also express protein markers used to identify natural killer (NK) cells.  What makes the iNKT cell invariant is its TCR α chain, which comes only in the version dubbed Vα14 in mice and Vα24 in humans.  Even the β chain of the TCR of iNKT cells is restricted to three types in mice and just one in humans.  The lack of variation is unusual because the α and β TCR chains of conventional αβ T cells come in many forms in each individual, resulting in millions of varieties of TCRs.  This enables conventional αβ T cells to recognize a wide range of microbial peptide antigens when displayed by an MHC molecule on the surface of an antigen-presenting cell (see figure below).  In contrast, the TCRs of iNKT cells recognize a limited set of glycolipids displayed by the antigen-presenting cell's CD1d molecule, which structurally resembles MHC.  So far these glycolipids have been found only in Sphingomonas and B. burgdorferi. Antigen recognition by T cells.  The "X" represents variable T cell receptor chains.Figure 1 from ref. 3.The structures of the B. burgdorferi glycolipids recognized by iNKT cells are shown below.  BbGL-IIc is recognized by mouse iNKT cells, and BbGL-IIf reacts with human iNKT cells.4Structures of B. burgdorferi glycolipid antigens recognized by iNKT cells.  Figure 3d from ref. 3.iNKT cells are activated when their TCR binds to BbGL-II complexed with CD1d.4  The activated iNKT cells secrete cytokines that elicit the appropriate immune response against the spirochetes.  How these cytokines promote killing of B. burgdorferi remains unknown.To view the process of iNKT cell activation, scientists have recently obtained video footage of the early stages of the immune response to Borrelia burgdorferi circulating in the bloodstream of mice.1  The study by Lee et al., which appeared in the April issue of Nature Immunology, complements two earlier studies that revealed how the Lyme disease spirochete escapes from the bloodstream of mice to invade the surrounding tissues.5,6The investigators employed fluorescence video microscopy to watch the immune cells in action following injection of an engineered B. burgdorferi strain expressing green fluorescent protein (GFP) into the bloodstream.  Although the spleen is better known for filtering bloodstream pathogens, the liver was selected for observation because iNKT cells make up 30% of the T cells in the liver.  In contrast, iNKT cells represent only 2.5% of T cells in the spleen.  Moreover, mice missing their spleen were able to limit B. burgdorferi infection as well as mice having a spleen, suggesting that the spleen is not critical in fighting bloodstream B. burgdorferi.iNKT cells reside in the liver's sinusoids, which are the specialized capillaries that carry blood through the liver.  Similar to what other investigators have observed, the authors saw iNKT cells creeping along the inner surface of the liver sinusoids in healthy mice (see video below).iNKT cells crawling within the liver sinusoids of a mouse genetically altered to express green fluorescent protein (GFP) in iNKT cells.  The iNKT cells glow bright green.  The elapsed time is shown at the top right.  Video 2 from ref. 1.The investigators wanted to figure out which of the antigen-presenting cells found in the liver presented borrelial glycolipid to iNKT cells.  The answer?  After the spirochetes were injected into the bloodstream, they were quickly captured by Kupffer cells, the specialized blood-filtering macrophages that also reside in the liver sinusoids (see figure below).  Unlike iNKT cells, Kupffer cell remained stationary.Capture of fluorescent B. burgdorferi (thin green bodies) by Kupffer cells (arrowhead).  Kupffer cells are stained red.  B. burgdorferi that avoided capture can be seen bound to the endothelium, trying to escape from the bloodstream into the liver tissue (arrow).  Figure 2e from ref. 1.During the next several hours, the captured spirochetes were engulfed and broken up by the Kupffer cells so that BbGL-II could be loaded onto CD1d and displayed on the cell surface.  At 8 hours post injection, iNKT cells started to cluster and form stable contacts with Kupffer cells.  The iNKT cells were attracted to Kupffer cells churning out the chemokine CXCL9, a potent iNKT cell attractant.  The evidence for this ... Read more »

Lee, W.Y., Moriarty, T.J., Wong, C.H.Y., Zhou, H., Strieter, R.M., van Rooijen, N., Chaconas, G., & Kubes, P. (2010) An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nature Immunology, 11(4), 295-302. DOI: 10.1038/ni.1855  

  • July 24, 2010
  • 02:22 PM

The great golden digger wasp, the Concorde fallacy, and free will

by Ryan Kitko in Cunabulum

Sphex ichneumoneus, the great golden digger wasp, about to enter her burrow.A few weeks ago, I noticed some alarmingly large insects that resembled wasps outside the front entrance of the biology building at Kenyon College. They would fly a few centimeters above the sandy gravel, no doubt surveying the best landing spot. Only a handful of these solitary wasps were here hovering over at least a dozen wasp-diameter holes in the loamy soils under this protected overhang. Suddenly, one landed and disappeared into her burrow. Ah! Digger wasps! I had read about them but never before observed them in the wild. Well, as wild as a well-manicured college campus is in the relative calm of summer. The wasps were a mixture of brilliant orange contrasted with a deep black color. Almost blue iridescent wings fluttered periodically as they danced around the burrows. After consulting available guides and experts in the natural sciences division at Kenyon, it was confirmed these are indeed the great golden digger wasps (Sphex ichneumoneus). These beautiful solitary wasps emerge in the summer and spend about 6 weeks building multiple burrows that they then provision with paralyzed katydids. When the female - the males do not assist in burrow building or provisioning - is satisfied with her stash, she lays a single egg and closes the burrow, commonly completing this process 10 times before her short adult life is over. This species is common to much of the United States, so it's not a surprise to find them here in Ohio.The sheltered gravel/sand area outside Higley Hall at Kenyon College is the perfect burrow building habitat for the great golden digger wasp.My usual curiosity of the natural world doesn't typically extend beyond plants, but my interest was piqued. When searching for information on species I have not encountered before, I am often disappointed. Indeed, the great many species out there have been described in full maybe once - the original description - and mentioned a handful of other times in other publications as simply being an associate of other species. It's unusual to find such a detailed account of the life history of a single species, but I was pleasantly surprised with Sphex ichneumoneus. This species and its relatives have been observed in great detail and their behavior has made our species ponder the nature of philosophical fallacies and free will. What a creature!Investment and returnOver six breeding seasons in the 1970s, H. Jane Brockmann recorded data of wasp behavior from three sites. Typically, each female will work on her own to dig and provision her burrow, but sometimes two females will begin provisioning the same nest in 5-15% of cases. The interloper takes advantage of the other wasp's spent investment and the two will be bringing katydids into the same nest. But because they spend most of their time away from the nest seeking new prey, it is only a coincidence if the two meet and fight over the nest. Fights last between 2 and 16 minutes and often the loser would leave and never return. Because of this one-on-one interaction where both insects have varying degrees of past interest (their future interests would be identical), the data can be thought of in simple game theory mechanics. The founding wasp took the time to dig the burrow and begin provisioning it, while the joiner risked being discovered and the subsequent fight to cheat and not build her own burrow. When faced with a fight, however, each has the same prize and motivation: a well-provisioned nest is worth fighting for, saving the winner days more of additional digging and hunting to lay a single egg.The "sunk cost fallacy," or Concorde fallacy, so named because the British and American governments continued to fund the faster trans-Atlantic Concorde flights even when there was no longer any economic incentive to do so, refers to decisions based on past investment because of loss aversion instead of on the rational potential future gains. Brockmann, along with Richard Dawkins, asked the question, "Do digger wasps commit the Concorde fallacy?" in their 1980 publication. The available evidence suggested that the wasp with the least prior investment in a burrow would give up first in a fight and abandon her effort. This result was not skewed by size advantage, which wasp visited the burrow most recently, or whether the winner was the founder or the joiner. Put plainly, the winner was usually the one who brought the most katydids to the burrow. As Brockmann and Dawkins say, "It is hard to resist the suspicion that the wasps are behaving as if following the Concorde fallacy." But are they?Number of katydids each fight participant brought. Nine fights were over empty burrows. From Dawkins & Brockmann, 1980.Further, the fight length was strongly dependent on how many katydids the loser brought. Falling into the Concorde fallacy, you might conclude that the loser will fight more vigorously because of greater prior investment in the burrow and less vigorously for those she has barely begun to provision. The losing wasp appears to rationalize: "Fight only as long as is proportional to your individual investment in this burrow." This case study informed the ongoing discussion of whether we humans consider such strategies to be "good" in our assessment relative to their evolutionary stability. The Concordian strategy versus the strict economist (fight based on potential future gain) is fully revealed here in this brilliant case study.Free willJust one more quick interesting note about these creatures. In Daniel Dennett's book Elbow Room, he reproduces an account by Woolridge in 1963 about the deterministic behavior of Sphex ichneumoneus. Woolridge watched the wasps return to their burrows with katydids, leaving them just outside while they went inside to inspect. Normally, the wasp is inside for a few seconds, then reemerges and drags the paralyzed katydid backward down into the burrow. He decided to alter the pattern to see if the wasp's behavior changed. When the wasp entered the burrow, Woolridge would subtly move the katydid a few inches from the burrow threshold. The wasp reemerged to find he prey moved, dragged it back to the threshold, then dove back into the burrow alone to inspect again. Woolridge writes, "On one occasion this procedure was repeated forty times, always with the same result." The wasp appears to be an unwilling participant in a free will experiment. She is not a free agent, but instead is driven by environmental cues: once a katydid is near the threshold, I must inspect the burrow and only then can I bring it inside. This property, an apparent lack of free will, was even given the name sphexishness. Dennett notes that publications on free will are rife with fears of sphexishness. Call it genetic determinism or a behavioral loop. Perhaps, though, we're all a little sphexish.And what of the wasps?I know their short adult lives will be over soon, but I've enjoyed viewing them through the window these past few weeks. Apparently, though, their lives were meant to be shorter than usual. I walked out the door the other day and noted the acrid smell of pesticides on the air. It got stronger as I approached the burrows and each hole was wet, as if it had been sprayed. Sphex ichneumoneus is a solitary wasp that is not inclined to sting anything but katydids. If you approach them or their burrows, they fly away, bothering no one. I was told our department administrative assistant tried to fill the holes in one day and I suspect she alerted the maintenance department to their presence, thus leading to their demise. Perhaps if people took the time to find out more about the supposed threat before eradicating it, they might change their minds about the course of action. That at least one good motivation for effective science education.... Read more »

DAWKINS, R., & BROCKMANN, H. (1980) Do digger wasps commit the concorde fallacy?. Animal Behaviour, 28(3), 892-896. DOI: 10.1016/S0003-3472(80)80149-7  

  • July 24, 2010
  • 12:09 PM

Are most experimental subjects in behavioral science WEIRD?

by Michael Meadon in Ionian Enchantment

My supervisor David Spurrett and I have a commentary on an important paper - "The weirdest people in the world?" (pdf) - in the most recent edition of Behavioral & Brain Sciences. The authors, Canadian psychologists Joseph Henrich, Steven Heine and Ara Norenzayan, argues that most experimental subjects in the behavioral sciences are WEIRD - Western, Educated, Industrialized, Rich, and Democratic - and thus weird - not representative of most human beings. And this, if true, is a very serious problem indeed. Behavioral scientists (anthropologists, psychologists, behavioral economists and so on) are often interested in explaining the brains, minds and behavior of Homo sapiens as a species. (Some scientists, of course, are only interested in understanding specific cultures or what makes us different, but one important goal of the behavioral sciences has long been to explain universal human behavior). As evolutionary psychologists John Tooby and Leda Cosmides have put it, they "seek to characterize the universal, species-typical architecture of [the information-processing mechanisms that generate behavior]".

But... Henrich and his colleagues review a large body of literature that seems to show that, across several domains, Western undergraduates - the workhorses of the behavioral sciences - are extreme outliers. In other words, if they are correct, most of the data behavioral scientists have used to test hypothesis and drive theorizing have been derived from subjects who are possibly the least suited for generalizing about the human race. Take as an example the Müller-Lyer illusion. In the diagram below, the lines labeled "a" and "b" are exactly equal in length, but many subjects perceive "b" as longer than "a".

This finding (which goes back all the way to 1889) has been used to make deductions about how the human visual system works. The Wikipedia article on the illusion, for example, states that one possible explanation for the effect is that "the visual system processes that judge depth and distance assume in general that the 'angles in' configuration corresponds to an object which is closer, and the 'angles out' configuration corresponds to an object which is far away". Plausible enough. Except that for some people - San foragers, for example - the illusion does not exist, and in many other non-WEIRD societies the effect size is significantly smaller. Henrich and his colleagues cite the work of Segall et. al. (1996), who worked out the magnitude of the illusion across 16 societies by varying the relative lengths of "a" and "b" and then asking subjects to indicate when they thought the lines were equal. The percentage by which "a" must be longer than "b" before the lines are adjudged equal - what they call the "point of subjective equality" (PSE) - varies substantially between subjects from different cultures - and, importantly, WEIRD-subjects are extreme outliers. The results are summarized in the following graph:

Both WEIRD adults and children (aged 5-11) require "a" to be 18%+ longer than "b" before they're perceived as equal, but for the San and South African miners, the illusion simply does not exist - their PSEs are not statistically distinguishable from 0. Why this difference arises is unknown, but Segall et. al. claim it is due to WEIRD people's visual systems developing differently because modern environments expose them to ("unnatural") shapes like 'carpeted corners', thus calibrating their visual systems in a way that favors the emergence of the illusion. Whatever the true explanation, however, it is clear that it is not permissible to use the existence of the illusion among WEIRD subjects to make inferences about the visual system. This is especially true since the San subjects were hunter-gatherers, just like all people for the vast majority of human evolutionary history. Given that species-typical features of the visual system would have evolved in this period, it is particularly telling that PSE seems to be positively correlated with the 'modernity' of the societies in question. (Warning: this is an "eyeball" observation; I haven't done a proper statistical analysis. Caveat emptor).

This is one example from an extremely long paper, but it conveys a flavor of the kind of evidence the authors present. (For much more, see "We agree it's WEIRD, but is it WEIRD enough?" over at Neuroanthropology). Having read the article very carefully, and despite some concerns, I think Henrich, Heine and Norenzayan are right: the Western undergraduate is often unrepresentative of humanity, and the behavioral science literature needs a lot of fixing as a result. (Most obviously, we need far more large, highly-powered, globally representative, prospectively designed, cross-cultural studies). Serious as this is, unfortunately, it gets worse... Since David and I worked extremely hard to present our argument clearly and concisely in our commentary (pdf - our piece starts on p. 44 of the pdf, paginated by BBS as p. 104), and I doubt I could improve on it, what follows is a slightly edited - simplified and somewhat de-academicized - version of the meat of our argument. (Note: each issue of BBS consists of a "target article" - in this case, Henrich et. al. - and 20 or so short peer-commentaries).

Henrich et al. underplay – to the point of missing – that how the behavioural sciences research community itself is constituted introduces biases. That the subject-pool of behavioural science is so shallow is indeed a serious problem, but so is the fact that the majority of behavioural researchers are themselves deeply WEIRD. People in Western countries have, on average, a remarkably homogeneous set of values compared to the full range of worldwide variability (Inglehart & Welzel 2005), and the data Henrich and his colleagues present suggest similarly population-level homogeneity in cognitive styles. Moreover, academics are more uniform than the populations from which they are drawn, so it is likely behavioral scientists are even WEIRDer than their most common subjects. Henrich and his colleagues review a bunch of studies and experiments that did not strike those who designed and conducted them as focused on outliers. Intelligent scientists acting in good faith conducted, peer-reviewed, and published this research, in many cases honestly believing that it threw light on human nature. This forcefully illustrates the power of the biases on the part of researchers themselves. It also suggests that, besides widening the pool of subjects, there are significant gains to be made by broadening the range of inputs to the scientific process, including in the conception, design, and evaluation of empirical and theoretical work. Given that diverse groups are demonstrably better at some kinds of problem solving, as things stand, the WEIRD-dominated literature is robbed of potentially worthwhile perspectives, critiques, and hypotheses that a truly global research community could provide. Clearly, simply increasing the number of behavioural sciences&nbs... Read more »

Henrich, J., Heine, S., & Norenzayan, A. (2010) The weirdest people in the world?. Behavioral and Brain Sciences, 33(2-3), 61-83. DOI: 10.1017/S0140525X0999152X  

  • July 24, 2010
  • 11:57 AM

Adventures with Citizen Science: perspectives of a shark biologist

by WhySharksMatter in Southern Fried Science

Those of you who follow me on Twitter or are friends with me on facebook may have seen that last month, I asked for volunteers to come catch and tag sharks with me here in Charleston. While I was pleased by how excited respondents were for this opportunity, I would be remiss if I didn’t [...]... Read more »

  • July 24, 2010
  • 10:32 AM

How to maxmize your happiness from a vacation.

by Psychothalamus in Psychothalamus

I am sure that most, if not all of us would agree that going on a vacation makes us happy. But are we really happier than people who are not going for a holiday? And if we are indeed happier, how long do these effects persist and how does the length of our vacation and amount of holiday stress impact our happiness levels? These are some of the questions that Nawijn, Marchand, Veenhoven & Vingerhoets (2010) attempt to answer.Their main findings are listed below.Pre-trip happiness: Vacationers (n=974) displayed significantly higher degrees of happiness than non-vacationers (n-556) Post-trip happiness: Vacationers were generally not significantly happier than non-vacationers. Only vacationers who rated their holidays as very relaxed (as opposed to relaxed, neutral, stressful or very stressful) had significantly higher degrees of happiness for the first 2 weeks after the vacation.Length of vacation was not associated with post-trip happiness.*Note: The vacation began between week 27 and week 35.So what do these findings tell us about how we should plan our vacations?For starters, the planning and anticipation of the upcoming vacation makes us much happier folks than those who are not looking forward to a vacation.The second finding, in line with the set point theory of happiness, indicates that once we are back from a vacation, our happiness returns rapidly back to baseline levels. Only the 'very relaxed' vacationers get an additional 2 weeks boost of happiness. So if you want that extended endorphins kick, make sure that you are really relaxed during the vacation.The last finding, together with the first two findings, suggests that in order to derive the most happiness out of your vacation, it would be better to take multiple short trips rather than a long trip. Since the length of the vacation is not associated with happiness, you'll get the most bang for your buck by enjoying the pre-trip happiness generated from planning and anticipating multiple trips.In sum:Enjoy the planning processDo your best to make your trip very relaxing (a trip that is just 'relaxed' doesn't quite cut it)Multiple short trips are better than one long tripNawijn, J., Marchand, M., Veenhoven, R., & Vingerhoets, A. (2010). Vacationers Happier, but Most not Happier After a Holiday Applied Research in Quality of Life, 5 (1), 35-47 DOI: 10.1007/s11482-009-9091-9... Read more »

Nawijn, J., Marchand, M., Veenhoven, R., & Vingerhoets, A. (2010) Vacationers Happier, but Most not Happier After a Holiday. Applied Research in Quality of Life, 5(1), 35-47. DOI: 10.1007/s11482-009-9091-9  

  • July 24, 2010
  • 08:55 AM

Why moss blows smoke rings

by Thomas Kluyver in Thomas' Plant-Related Blog

Science via Youtube today. Let’s start with some smoke rings.  They go an impressively long way—much further than a simple puff of smoke fired with the same force would: So, why might a moss need to do the same thing? It’s all about spores. Mosses spread by spores, a bit like microscopic seeds. For peat [...]... Read more »

  • July 23, 2010
  • 11:55 PM

MDMA for PTSD: The first peer-reviewed clinical trial report

by DrugMonkey in DrugMonkey

My readers will recall that I have blogged now and again about ongoing efforts to get 3,4-methylenedioxymethamphetamine (MDMA), the psychoactive compound preferentially sought as Ecstasy in recreational users, approved as a medication to be used in psychotherapy. The initial attempts have focused on the treatment of Post-Traumatic Stress Disorder. PTSD is a seriously debilitating condition and we may not have sufficient resources and knowledge to deal with, e.g., an anticipated uptick due to the current wars that the US is prosecuting.

I introduced the MDMA/PTSD Phase I clinical trials here, noting
The short version of the theory is that the subjective properties of MDMA (empathic, inhibition lowering, etc) are consistent with helping people in difficult psychotherapeutic situations (such as for post-traumatic stress disorder (PTSD) and, supposedly, end stage cancer anxiety) make therapeutic breakthroughs during a limited number of treatment sessions of talk therapy. This is not proposed as a chronic medication like a selective serotonin reuptake inhibitor (SSRI). The funny thing is, I approve of the concept of moving forward with clinical trials based on the available evidence.

Why not? I mean PTSD can be a very devastating psychological issue and if there are treatment-resistant cases that can benefit from a limited number of MDMA exposures, great.

I concluded that particular post with this observation.
As is general practice in medicine, sometimes there are going to be risks associated with therapy. Sometimes quite substantial risks can be acceptable if the alternative is bad. However we get ourselves into a world of trouble, sometimes even losing a perfectly helpful medication, if we are not as honest as possible, up front, over the actual risks. My subsequent attentions have been lavished upon what I see as a lack of recognition/admission of potential risk factors associated with intake of MDMA, particularly in context of the trend for pushing the doses ever upward as the clinical trials continue.

I have also been critical of what I saw as rather half-baked mechanistic theorizing for how MDMA might produce a therapeutic effect. After all, if this is neurobiologically real there should be a mechanistic explanation for why this drug is so special. How is it better than an antidepressant or stimulant? Or a traditional hallucinogen for that matter? MDMA shares pharmacological properties will all these drug classes, albeit in its own unique constellation of pharmacocomplexity.

In other posts I've covered issues related to drawing inferences about likely human outcomes from the doses used in animal studies here andhere. These observations follow on from an earlier discussion of how we should view the doses of MDMA being used in the context of the likely range of human subjects-from an average sized adult woman to a large male warfighter.

There was aready an interesting preview of the study to be found in a non-peer reviewed protocol made available by the research team. It is nice, however, to finally see the peer-reviewed article by Mithoefer and colleagues appear in the Journal of Psychopharmacology. This study is described in the Introduction as being a "pilot Phase II" trial. This means we are not merely looking at the safety and useful dose range (as with a Phase I trial) but are interested in efficacy. Does the proposed medication actually work? This is a "pilot" I suppose because traditionally 20-30 subjects would be a Phase I trial and a Phase II really expects more like 100 or more.

The authors do speculate on the potential mechanism of action in the Introduction but it is unsatisfying, as with that prior paper. Yes, the indirect serotonin agonist properties are linked to the subjective properties- properties that seem to include empathy, openness to others, lack of fear, etc. A perfectly reasonable-sounding psychodynamic effect, no doubt, but then what is so special about MDMA? They speculate on the oxytocin enhancement that is a downstream effect of serotonin release and about fear conditioning circuitry of the ventromedial PFC and amygdala. Again, I'm not seeing why MDMA is so special.

The design of this study examined 20 PTSD patients who met SDM-IV-R criteria for crime- or war-related Post-Traumatic Stress Disorder and had a Clinician Administered PTSD Scale (CAPS) score of 50 or greater (moderate to severe symptoms). In addition, patients had to have had a minimum prior course of 6 mo of psychotherapy and 3 mo of treatment with either a Selective Serotonin Reuptake Inhibitor (SSRI; e.g., prozac) or Selective Norepinephrine Reuptake Inhibitor (SNRI) compound. Individuals visited the clinic on at six occasions- a baseline evaluation, two experimental therapy sessions, followup evaluation visits 3-5 days after each therapy session and a final evaluation 2 months later.

Twelve patients (10 F) were assigned to MDMA-treatment (125 mg initial dose; 4 rec'd 62.5 mg supplemental dose 2-2.5 hrs later) and 8 (7 F) to inactive placebo treatment conditions. The average age was about 40 years and all subjects were described as Caucasian. There was only a single individual whose index trauma was combat stress (assigned to MDMA) and the majority were sexual assault and childhood sexual or physical abuse.

Figure3: Time 1: less than 4 weeks
before first experimental session;
Time 2: 3-5 days after first experimental
session; Time 3: 3-5 days after second
experimental session; Time 4: 2 months
after second experimental sessionAs depicted in Figure 3 from the article, the CAPS scores declined in both groups, however to a much greater extent in the MDMA-assigned group. Main effects of Time and Treatment Group, as well as the interaction, were reported in the statistical analysis.

So yes, this study shows efficacy of MDMA treatment in the course of a structured psychotherapeutic session for PTSD.

In terms of major limitations to this study, the first has to do with blinding of the treatment condition. I don't really wish to go into expectancy, confidence in the efficacy of the therapeutic modality (ala E. Fuller Torrey), placebo effects and all that. Suffice it to say that for the highest confidence we would wish for successful blinding. It failed utterly in this study, perhaps unsurprisingly. The therapists identified the treatment condition for all subjects and 19/20 of the patients correctly identified the condition they were in. Not blinded in the least. This does not make the study useless, it just puts an additional consideration into our interpretation.

A second moderate limitation is that the subjects were treatment resistant and had previously been on SSRI medications. Since these chronic treatments induce some degree of plasticity of the serotonergic system, and a major effect of MDMA is on serotonin systems and indeed the Reuptake mechanism for which SSRIs are named, well, there are some things to think about. Throw in the original lack of response to SSRI and one wonders about the pre-therapy state of these patients' serotonergic function relative to those who respond to SSRI therapy. Not a huge knock on this early stage study of course. I mean, if you are going to get a recreational drug with known neurotoxic and acute toxicity risk approved as adjunct it is going to have to beat existing medications in some way. Starting with the population that remains untreated despite the best current therapy is an obvious place to start. Still, from a neuropharmacological standpoint it makes this study le... Read more »

  • July 23, 2010
  • 11:47 PM

Jellyfish: Pretty from a Distance

by Kevin Zelnio in Deep Sea News

Photo from Dan Herschman's Flickr Stream (Click on Image).
A link from one of readers (thanks Ashley!) pointed us to a story on MSNBC about a very large Lion’s Mane jellyfish (Cyanea capillata) that broke apart and stung up to 100 people on a New Hampshire beach last Wednesday. Lion’s Manes can get very big, their . . . → Read More: Jellyfish: Pretty from a Distance... Read more »

Nüchter, T., Benoit, M., Engel, U., Özbek, S., & Holstein, T. (2006) Nanosecond-scale kinetics of nematocyst discharge. Current Biology, 16(9). DOI: 10.1016/j.cub.2006.03.089  

  • July 23, 2010
  • 10:54 PM

Viruses are objectively better than bacteria – DotW throwdown

by thomastu in Disease Prone

I am throwing down the gauntlet. James, you sir, have insulted my and my discipline’s honour for the last time. Time for a good ol’ fashion debate. Here and now, let the readers be the judge. Have at you, sirrah! Viruses are better than bacteria. I really shouldn’t have to say this; it is almost [...]... Read more »

Pearson, H. (2008) 'Virophage' suggests viruses are alive. Nature, 454(7205), 677-677. DOI: 10.1038/454677a  

  • July 23, 2010
  • 10:35 PM

Hippocampal ripples and memory consolidation

by 神経オタク in Cognitive Convolutions

So the vos Savant post got me thinking... I'm kind of comfortable talking about sleep (or at least, comfortable enough to get in trouble, I'm sure), and would love to make a few more posts on it. And, hey, why the hell not? I'm sure some of my friends would like to see what I read, and why not start making occasional research posts out of it? Who knows; if even one or two readers get something... Read more »

  • July 23, 2010
  • 08:19 PM

Major depression associated with impaired processing of emotion in music?

by Maria P. in noustuff

Previous studies have found that the processing of faces and voices is negatively biased in major depression. Naranjo and colleagues were the first to investigate possible effects of major depression on the recognition of emotion in music. According to the authors: as music is not directly linked to interpersonal communication, comparing a musical task with [...]... Read more »

Naranjo, C., Kornreich, C., Campanella, S., Noel, X., Vandriette, Y., Gillain, B., de Longueville, X., Delatte, B., Verbanck, P., & Constant, E. (2010) Major depression is associated with impaired processing of emotion in music as well as in facial and vocal stimuli . Journal of Affective Disorders. info:/10.1016/j.jad.2010.06.039

  • July 23, 2010
  • 03:13 PM

Theme Science

by Erika Cule in Blogging the PhD

Wikipedia tells me that they are know as Construction and Management Simulation games. (Who knew? I didn't!) I used to love playing them, and if the image of an 11-year-old kid engrossed in SimCity seems a little incongruous, perhaps that...... Read more »

  • July 23, 2010
  • 02:40 PM

Autism Spectrum Predicts Poor Outcome in Anorexia Nervosa

by William Yates, M.D. in Brain Posts

Few studies have examined the long-term outcome after the diagnosis of anorexia nervosa.  Fewer still have focused on adolescent-onset anorexia nervosa.Wentz and colleagues from Goteborg Sweden conducted a case-control study of 51 girls with anorexia nervosa with an average age of onset of 14 years old.Outcome studies in eating disorders often vary based on the site of recruitment.  Community samples typically have the most favorable prognosis followed by those identified in outpatient samples.  Subjects identified through inpatient hospitalization typically have the poorest outcome.  This is likely due to a severity of illness confounding effect.  More severe illness typically predicts a poorer outcome.The Swedish study used a community sample and so it was not surprising they found a relatively favorable outcome.  The outcome data in this study included:12% still had an active eating disorder 18 years later39% met criteria for at least one psychiatric disorder 18 years laterDuring the entire follow-up period 67% experienced a major depression, 73% met criteria for an anxiety disorder (obsessive-compulsive disorder and generalized anxiety most common types)25% were unemployed due to a psychiatric disorderPoor outcome was associated with several factors:Younger age of onset of anorexia predicted longer duration of anorexiaLower weight (BMI) Obsessive-compulsive personality disorderChildhood autism-spectrum disorder before anorexiaThis is one of the few studies that identified autism-spectrum disorder as a negative prognostic variable in anorexia nervosa.  Autism and anorexia share some abnormalities in oxytocin markers and brain left hemisphere predominance.  Odent has proposed autism and anorexia may share a common mechanism related to prenatal hormone exposure.There were no deaths in this sample over the 18 years of followup.  Increased mortality has been common in other outcome studies of eating disorders.Anorexia nervosa appears to have a variable outcome with better prognosis in community samples.  However, even in community samples, psychiatric comorbidity is common and influences outcome.  Autism-spectrum disorder is a comorbid condition that deserves further study.Photo of Canadian goose courtesy of Yates Photography.Wentz, E., Gillberg, I., Anckarsater, H., Gillberg, C., & Rastam, M. (2009). Adolescent-onset anorexia nervosa: 18-year outcome The British Journal of Psychiatry, 194 (2), 168-174 DOI: 10.1192/bjp.bp.107.048686Odent M (2010). Autism and anorexia nervosa: Two facets of the same disease? Medical hypotheses, 75 (1), 79-81 PMID: 20176449... Read more »

Wentz, E., Gillberg, I., Anckarsater, H., Gillberg, C., & Rastam, M. (2009) Adolescent-onset anorexia nervosa: 18-year outcome. The British Journal of Psychiatry, 194(2), 168-174. DOI: 10.1192/bjp.bp.107.048686  

  • July 23, 2010
  • 01:16 PM

Sweet sensors

by sciencebase in Sciencebase Science Blog

Nothing new under the sun, as the bard said, and how true it is sometimes. No sooner had I posted a news article on entitled “Sweet sense of GOD” than Santhosh Challa, a Senior Scientist at Merck & Co in New Jersey, USA, got in touch to tell me that his team had also [...]Sweet sensors is a post from: Sciencebase Science Blog
... Read more »

  • July 23, 2010
  • 12:39 PM

Quantum Mechanics Is Square: "Ruling Out Multi-Order Interference in Quantum Mechanics"

by Chad Orzel in Uncertain Principles

This week's big story in physics is this Science paper by a group out of Austria, on a triple-slit interference effect. This has drawn both the usual news stories and also some complaining about badly-worded news stories. So, what's the deal?

What did they do in this paper? The paper reports on an experiment in which they looked at the interference of light sent through a set of three small slits, and verified that the resulting pattern agrees with the predictions of the Born rule for quantum probabilities.

What does Matt Damon have to do with quantum physics? Born, not Bourne. Specifically, Max Born, a German physicist who worked out the connection between quantum wavefunctions and observable probabilities.

Okay, what? Allow me to explain. Actually, there's too much to explain, so let me sum up. Read the rest of this post... | Read the comments on this post...... Read more »

Sinha, U., Couteau, C., Jennewein, T., Laflamme, R., & Weihs, G. (2010) Ruling Out Multi-Order Interference in Quantum Mechanics. Science, 329(5990), 418-421. DOI: 10.1126/science.1190545  

  • July 23, 2010
  • 11:36 AM

When bivalves attack (or: bivalves vs birds, the battle continues)

by Darren Naish in Tetrapod Zoology

Regular readers will, hopefully, have shared my surprise on learning - firstly - that oystercatchers are sometimes 'captured' and killed by bivalves, and - secondly - that someone was clever enough to photograph such an occurrence and publish it (Baldwin 1946). Prior to seeing Baldwin's paper, I might well have imagined that such cases can occur occasionally, but I wasn't aware of anyone recording them.

Today I'm very pleased to report that I'm now aware of numerous additional such occurrences: I owe a huge debt of thanks to Tet Zoo regular Dartian, who went ferreting through the ornithological literature on my behalf. As you'll see, he turned up some real gems. We can now say that sea- and wading birds of many different kinds are known to have been 'captured', disabled or even killed by bivalves on occasion. These occurrences are still comparatively rare, but they're far more numerous than I would previously had thought. Read the rest of this post... | Read the comments on this post...... Read more »

Tsipoura, N., & Burger, J. (1999) Shorebirds and Surf Clams: An Unusual Interaction. Waterbirds: The International Journal of Waterbird Biology, 22(1), 140. DOI: 10.2307/1522003  

  • July 23, 2010
  • 11:32 AM

Protein Function: how do we know that we know what we know?

by Iddo Friedberg in Byte Size Biology

The trouble with genomic sequencing, is that it is too cheap. Anyone that has a bit of extra cash laying around, you can scrape the bugs off your windshield, sequence them, and write a paper. Seriously?

Yes, seriously now: as we sequence more and more genomes, our annotation tools cannot keep up with them. It’s like unearthing thousands of books at some vast archaeological dig of an ancient library, but being able to read only a few pages here and there. Simply put: what do all these genes do? The gap between what we do know and what we do not know is constantly growing. We are unearthing more and more books (genomes) at an ever-increasing pace, but we cannot keep up with the influx of new and strange words (genes) of this ancient language. Many genes are being tested for their function experimentally in laboratories. But the number of genes whose function we are determining using experiments is but a drop in the ocean compared to the number of genes we have sequenced and whose whose function is not known We may be sitting on the next drug target for cancer or Alzheimer’s disease, but those proteins are labeled as “unknown function” in the databases.... Read more »

Godzik, A., Jambon, M., & Friedberg, I. (2007) Computational protein function prediction: Are we making progress?. Cellular and Molecular Life Sciences, 64(19-20), 2505-2511. DOI: 10.1007/s00018-007-7211-y  

  • July 23, 2010
  • 11:13 AM

Methods Fail: Testing the pre-menopausal cougar hypothesis.

by EcoPhysioMichelle in C6-H12-O6 (old)

ScienceDaily has an article from earlier this month, Ticking Biological Clock Increases Women's Libido, New Research Shows, that claims that women who are approaching menopause become "more willing to engage in a variety of sexual activities to capitalize on their remaining childbearing years" and that they are more prone to one night stands and "adventurous bedroom behavior" than their younger counterparts.... Read more »

  • July 23, 2010
  • 10:53 AM

The will and its freedom: biological evidence from invertebrates

by Björn Brembs in

A few weeks ago, Lars Chittka invited me to write an article "about free will in insects" for a Proceedings of the Royal Society B (Biological Sciences) Special Feature on 'Information processing in miniature brains' that he is editing. Given our work on spontaneity in flies and my mentor being Martin Heisenberg, how could I decline?I think I will first give a very brief overview of what people used to call "free will" and why it was such a controversy. I hope to get the gist across in about two paragraphs. Much of this info will be distilled from Bob Doyle's website and his article in William James Studies. Bob also published a letter to Nature in response to Martin Heisenberg's article there. Is it just coincidence that it was Heisenberg's father Werner Heisenberg who discovered the uncertainty principle?Then I plan to go on to argue that today the old, metaphysical free will of course does not exist in the almost 'spiritual' sense and that no prominent scholar has entertained that idea at least since Popper and Eccles' book "The self and its brain" in 1977. Instead, I will try and make the case that the term "free will" should be recast in biological terms, as a trait that evolved and keeps evolving to different degrees in different animals. I plan to use evidence from flies, leeches and other invertebrate animals to emphasize that even so-called 'simple' brains possess the capacity to behave unpredictably, i.e., freely. Any difference in freedom between animals is merely gradual.I probably should also spend a paragraph or so elaborating on the selection pressures leading to spontaneous behaviors and behavioral variability.Once the capacity for freedom has been shown, it will take less work convincing the readers of the capacity to 'will'.All of this should be couched in the notion that the dichotomy between indeterminism and determinism is a false dichotomy, because brains operate in the gray area between the two. This may be the most difficult concept to grasp, that indeterminism and determinism are not mutually exclusive, but delineate a spectrum of what one may call 'probabilism'. I may try and refer to evolution as also using both concepts of mutation (indeterminate) and selection (determinate) in a probabilistic process. I may even try and refer to Bayesian Statistics, although I know little more than the basic idea behind it. The main task of this section will be to argue that what we call freedom is more than just chance. Chance, or randomness is a prerequisite for freedom, a necessary component but it's not sufficient. Let me quote from our press release at the time: [co-author George Sugihara]"This nonlinear signature eliminates the two alternative explanations of spontaneous turning behavior in flies that would run counter to free will, namely complete randomness and pure determinism. These represent opposite and extreme endpoints in discussions of brain functioning which mirror the free will debate." To that, I'd only add that our subjective notion of 'Free Will' is essentially an oxymoron: we would not consider it 'will' if it were completely random and we would not consider it 'free' if it were entirely determined. Nobody would attribute any responsibility to our action if it had happened entirely coincidental. On the other hand, if our action was completely determined by external factors such that there was no alternative, again the person would not be held responsible. So if there is anything remotely close to free will, it must exist somewhere between chance and necessity - which is exactly where fly behavior comes to lie. George again finds the right words: "Our results address the middle ground between simple determinism and randomness that is currently not well understood or characterized. We speculate that if free will exists, it is in this middle ground." This leads me to believe that the question of whether or not we have free will appears to be posed the wrong way. Instead, if we ask 'where between chance and necessity are we located?' one finds that this is precisely where humans and animals differ. Humans may not have free will in the philosophical sense, but even flies have a number of behavioral options they need to decide between. Humans are less determined than flies and possess even more options. With this small reformulation, the topic of free will becomes the new biological research area of studying spontaneous behavior and can thus be discerned from the philosophical question.If after all that there's still room in the article, I'll review some of the data on the human default mode network and what they might contribute to the debate.Let's see, if enough people express interest in the comments, I may put a draft version online for comments and review. All commenters will at least be mentioned in the acknowledgements, of course.Heisenberg, M. (2009). Is free will an illusion? Nature, 459 (7244), 164-165 DOI: 10.1038/459164aDoyle, R. (2009). Free will: it's a normal biological property, not a gift or a mystery Nature, 459 (7250), 1052-1052 DOI: 10.1038/4591052cBriggman, K. (2005). Optical Imaging of Neuronal Populations During Decision-Making Science, 307 (5711), 896-901 DOI: 10.1126/science.1103736... Read more »

  • July 23, 2010
  • 09:36 AM

Acid Test

by Journal Watch Online in Journal Watch Online

Twenty years after the United States moved to take the sting out of acid rain, researchers are getting a clearer picture of how the pollution affected life in sensitive waters. A detailed new survey of lakes in the Adirondack mountains of New York State finds that acidification has caused species losses in every link of […] Read More »... Read more »

Nierzwicki-Bauer, S., Boylen, C., Eichler, L., Harrison, J., Sutherland, J., Shaw, W., Daniels, R., Charles, D., Acker, F., Sullivan, T.... (2010) Acidification in the Adirondacks: Defining the Biota in Trophic Levels of 30 Chemically Diverse Acid-Impacted Lakes. Environmental Science , 2147483647. DOI: 10.1021/es1005626  

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