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  • September 2, 2010
  • 05:58 AM
  • 26 views

Going under and coming to

by admin in Thoughts on thoughts



PLoS One has a paper, A Conserved Behavioral State Barrier Impedes Transitions between Anesthetic-Induced Unconsciousness and Wakefulness: Evidence for Neural Inertia, by Friedman and others here.
The abstract:
One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these [...]... Read more »

  • August 27, 2010
  • 04:40 PM
  • 111 views

Walking sub-optimally is the way forward

by Carl in The motor chauvinist

Today we’re going to do something a little different. I’ve been posting a lot about reaching movements, because that’s what I’m most interested in, but it may surprise you to learn that humans do actually have the capacity to move other parts of their bodies as well. I know, I’m as shocked as you are… so! The paper I’m going to cover is about the regulation of step variability in walking. It’s a little longer and more complex than normal, so strap yourselves in.Walking is a hard problem, and we’re not really sure how we do it. Like reaching, there are many muscles to coordinate in order to make a step forward. Unlike in arm reaching, these coordinated steps need to follow one another cyclically in such a way as to keep the body stable and upright while simultaneously moving it over terrain that might well be rough and uneven. Just think for a moment about how difficult that is, and what different processes might be involved in the control of such movements.One question that remains unanswered is how we control variability in walking. It’s a simple matter to control average position or velocity, but the variation in these parameters between steps is still unexplained. It is pretty well established that over the long-term people tend to try to minimize energy costs while walking – hence the gait we learn to adopt over the first few years of life. But there’s evidence that such a seemingly “optimal” strategy is not the whole story.Consider walking on a treadmill. What’s the primary goal of continuous treadmill walking? Well, it’s to not fall off. The researchers in the article took that idea and reasoned that because the treadmill is moving at a constant speed, the best way not to fall off is to move at a constant speed yourself. That’s not the only strategy of course – you could also do something a little more complicated like make some short, quick steps followed by some long, slow ones in sequence, which would also keep you on the treadmill.To test how the parameters varied, the researchers used five different walking speeds. You can see this in the figure below (Figure 3 in the paper):Human treadmill walking data with speed as percentage of preferred walking speed (PWS)L is stride length, T is stride time and S is stride speed. So A-C in the figure show how these values change with the five different treadmill speeds – length increases, time decreases and speed increases. D-F show the variability (σ) in these different parameters. G-I show something slightly more complex: a value called α that is defined as a measure of persistence, i.e. how much or little the parameters were corrected on subsequent strides. Values of α > ½ mean that there was less correction, whereas values < ½ mean that there was more correction. So panels G-I show that variability in stride length and time were not generally corrected quickly, but that variations in stride speed were.Read that last paragraph through again to make sure you get it. It will be important shortly!So: now we have a measure of human walking parameters. The question is, how are these parameters produced by the motor control system? That is, what does the system care about when it initiates and monitors walking? Well, one thing we can get from the data here is that the system seems to care about stride speed, but doesn’t care about stride time and stride length individually. And if that’s the case, then as long as the coupled length and time lie on a line that defines the speed, the system should be happy. A line a bit like this (figure 2B in the paper):Human stride parameters lie along line of constant speedThe figure shows the GEM (which stands for Goal Equivalent Manifold, essentially the line of constant speed) plotted against stride time and stride length. The red dots show some data. Right away you can see that the dots generally lie along the line. Ignore the green arrows, but do take note of the blue ones – they’re showing a measure of deviations tangent to (δT) and perpendicular to (δP) the line. Why is δT so much bigger than δP? Because perpendicular variations push you off the line and thus interfere with the goal, whereas tangential variations don’t. So the system is either not stepping off the line much in the first place or correcting heavily when it does.Here’s one more figure (Figure 5C and D in the paper) showing the variability (σ) and persistence (α) for δT and δP :Variability and persistence of deviationsYou can see that δT is much more variable than δP, as you might expect from the shape of the data shown in the second figure. You can also see something else, however: the persistence for δP is less than ½, whereas the persistence for δT is greater than ½. Thus, the system cares very much about correcting not just stride speed but the combination of stride time and stride length that take the stride speed away from the goal speed.Great, you may think, a lot of funny numbers to tell us that the system cares about maintaining a constant speed when it’s trying to maintain a constant speed! What do you scientists get paid for anyway? The cool thing about this paper is that the researchers are trying to figure out precisely how the brain produces these numbers. It turns out that if you just use an ‘optimal’ model that corrects for δP while ignoring δT, you don’t get the same numbers. So that can’t be it. How about if you specify in your model that you have to keep at a certain speed – say the same average speed as in the human data? That doesn’t work either. The numbers are better, but they’re not right.The solution that seems to work best is when the deviations off the GEM line (i.e. δP) are overcorrected for. This controller is sub-optimal, so basically efficiency is being sacrificed for tight control over this parameter. Thus, humans don’t appear to simply minimize energy loss – they also perform more complex corrections depending on the task goal.I’ve covered in a previous post the inkling that this might be the case; while we do tend to minimize energy over the long term, in the short term the optimization process is much more centred around the particular goal, and people are very good at exploiting the inherent variability in the motor system to perform the task more easily. This paper does a great job of testing these hypotheses and providing models to explain how this might happen. What I’d be interested to see in the future is an explanation of why the system is set up to overcorrect like that in the first place – is it overall a more efficient way of producing movement than just a standard optimization over all parameters? Time, perhaps, will tell.---Dingwell JB, John J, & Cusumano JP (2010). Do humans optimally exploit redundancy to control step variability in walking? PLoS computational biology, 6 (7) PMID: 20657664Images copyright © 2010 Dingwell, John & Cusumano... Read more »

  • August 26, 2010
  • 05:14 AM
  • 66 views

You Read It Here First

by Neuroskeptic in Neuroskeptic

Remember the paper from 2009 about combining two different drugs in the treatment of depression?It was about a clinical trial in which patients were randomly assigned to get just one antidepressant, fluoxetine, or two - mirtazapine & fluoxetine, mirtazapine & venlafaxine, or mirtazapine & buproprion. The people who got two antidepressants did better.But as I said at the time, in a comment beneath my post about it...All the first 6 weeks shows is that mirtazapine is better than placebo. Everyone in the study got a non-mirtazapine antidepressant, so any improvement in the non-mirtazapine group (i.e. the fluoxetine alone group) could have been placebo, regression to the mean etc. The only placebo-controlled aspect was that some people got placebo mirtazapine and some people got real mirtazapine. Now Dr's El-Mallakh, Kaur and Lippmann have written in a Letter to The Editor of the American Journal of Psychiatry (where the original paper appeared) thatThere was no mirtazapine plus placebo study group. This comparison arm is necessary in order to be confident that the observed effect by the three combined treatments could not have been accomplished by mirtazapine as a single drug. The observation that mirtazapine alone was equivalent to fluoxetine or paroxetine alone in a previous study does not negate the need for a control in the Blier et al. study. Without such a control, one cannot assume that two antidepressant medications are more effective than mirtazapine alone.What I said - on 18th December 2009. The new Letter was "accepted for publication" in May 2010, and it's only just appeared.Am I just blowing my own trumpet? No. Well, a bit. But there's a serious point as well: internet comments are a much better medium for discussing and criticizing research than Letters To The Editor ever can be.Why? The Letter may have been a bit slower, but it's still out there, surely? Plus, it'll have been read by far more people. My post has got about 400 pageviews so far. I don't know how many people read the Letters page in the AJP, but I'd imagine it must be a good few thousand. So what's the problem?The problem is that it's too late. Papers get cited by other papers fast, they change minds even faster. This article's been out nearly a year, and I'm sure that in that time it will have convinced some psychiatrists to start their depressed patients on two drugs, rather than just one.Now I'm not saying they shouldn't do that. I don't know. Anyway, I'm not a doctor. But I stand by my comment that this paper shouldn't be what changes your opinion on that question; the design of the trial means it can't tell you that. And I think that's something that readers of the paper should have been told at the time, not 9 months later.What's the solution? I've written about this previously as well. Scientific journals should have open, blog-style comment threads attached to everything they publish, so that readers can say what they have to say, immediately. A number of major journals, e.g. the PLoS journals, some of the Nature ones, and the BMJ, already do this.From what I've seen, the standard of comments is extremely high. Sure, some are rubbish. But the rubbish ones are almost always obviously bad, so I don't think they'll be doing much damage. The good ones, on the other hand, are often extremely insightful - whether they are criticizing, or praising, of the paper.El-Mallakh RS, Kaur G, & Lippman S (2010). Placebo group needed for interpretation of combination trial. The American journal of psychiatry, 167 (8) PMID: 20693473... Read more »

El-Mallakh RS, Kaur G, & Lippman S. (2010) Placebo group needed for interpretation of combination trial. The American journal of psychiatry, 167(8). PMID: 20693473  

  • August 24, 2010
  • 08:17 PM
  • 56 views

Ep 135: Why do I sneeze at the Sun?

by westius in Mr Science Show

Do you sneeze at the Sun?

I do. My brother does. Both my parents do. In fact, we are a family of Photic Sneeze sufferers.

The Photic Sneeze Reflex (PSR), also known rather ridiculously as Autosomal Dominant Compelling Helioophthalmic Outburst (ACHOO) Syndrome (how long do you think it took researchers to figure out that acronym....) is a dominant genetic condition affecting around 10% of the population. When a sufferer moves from a region of darkness to a region of bright light - for instance, walking outside and looking at the Sun - multiple sneezes occur. Research into the disorder has yet to explain either its mechanism or an evolutionary reason for why it occurs. One theory is that there is a "short circuit" in the brain, with the stimulated optic nerve somehow triggering the sneeze reflex.

Professor Louis Ptáček runs the Laboratories of Neurogenetics at the University of California, San Francisco. The aim of the lab is to study familial disorders with strong genetic contributions, and thus localise and identify genes that cause human disease. Other conditions in which he is interested include migraine and epilepsy, and an intriguing condition whereby certain sounds cause seizures. He considers PSR to generally be a midly annoying condition, unless you are a combat pilot, where sneezing at the Sun could indeed be life threatening.

I had a really interesting chat to Louis about PSR, and I've left the recording a little longer than usual, as we were really able to explore some fascinating ideas involved with PSR - it was a great chat. Listen in to this show here (or press play below):



Other interesting write-ups of PSR include neurotopia and Scientific American.

This topic came in as part of my call for questions for Science Week, so thanks @lisushi for the question! I'll be putting up more blogs and podcasts to answer the other questions that came in over the next few weeks.

References:
Breitenbach RA, Swisher PK, Kim MK, & Patel BS (1993). The photic sneeze reflex as a risk factor to combat pilots. Military medicine, 158 (12), 806-9 PMID: 8108024 

Langer N, Beeli G, & Jäncke L (2010). When the sun prickles your nose: an EEG study identifying neural bases of photic sneezing. PloS one, 5 (2) PMID: 20169159 

MADIGAN, J., KORTZ, G., MURPHY, C., & RODGER, L. (1995). Photic headshaking in the horse: 7 cases Equine Veterinary Journal, 27 (4), 306-311 DOI: 10.1111/j.2042-3306.1995.tb03082.x

Songs samples in the podcast:
The Steve Wilson Band 
"Stare At The Sun"
from "Sideshows And Fairytales"
Buy at iTunes DJ Smiths vs Markanera
 "Watching the Sun Goes Down"
from "Watching the Sun Goes Down"
Buy at iTunes Alexis Cuadrado 
"Bright Light"
from "Puzzles"
Buy at iTunes

... Read more »

  • August 23, 2010
  • 08:30 PM
  • 23 views

Rats Pee During the Night. A Surprise? Not Really

by Allison in Dormivigilia

Researchers have behaviorally confirmed an entrained rhythm of urination in the rat. Though this information is consistent with the recent shift in funding focus in circadian research (i.e. funding crutches), this is an example of a study that doesn't take advantage of advanced neuroscience techniques or at least attempts to elucidate the mechanisms. I mean, gosh, it was published in PLoS.... Read more »

Gerald M. Herrera1,2, Andrea L. Meredith3*. (2010) Diurnal Variation in Urodynamics of Rat . PLoS ONE. info:/10.1371/journal.pone.0012298

  • August 19, 2010
  • 10:04 AM
  • 55 views

Where did the oil go?

by Sarah Stephen in An ecological oratorio

The recent oil spill in the Gulf of Mexico released, as we have all seen on tv, a lot of oil. Quite how much is a "lot" is a bit of a guess, but roughly 4.9 million barrels, or 784 million litres*. What actually happened to this oil was reviewed recently in an article in Science (Kerr 2010). Only about 0.1% was recovered from beaches and marshes (that´s still an awful lot of oil!). About 17% was siphoned away at the well head, 5% burned off at the surface, and only 3% skimmed off by booms, despite a lot of effort and money spent. And the other 75%? It's, er, disappeared.So where did this oil go? Some evaporated, but with luck most of it was eaten.Oil is energy, that's why we use it in our cars and power stations. And energy means food. There are actually quite a few bacteria that digest and breakdown crude oil, and these are massively important in the recovery of the ocean from disasters like this. They work as a consortium, each concentrating on a particular fraction of the oil, and as one hydrocarbon is degraded to another, other bacteria take over. The first, and so in many ways the most important, are Alcanivorax species (Vila et al 2010). These are found in tiny quantities in unpolluted waters, but their numbers rocket when in the presence of linear and branched alkanes, common in crude oil. In fact they are so specialised for this type of hydrocarbon that without long chain alkenes they grow very poorly, but by then their job is done. Now other species such as Roseovarius and Marinobacter take over.This breakdown was helped by the massive release of chemical dispersants at the oil head, 1.1 million gallons (Kintisch 2010). These are similar to the detergent in your kitchen, breaking down lumps of oil into tiny droplets, which are "dispersed" and can be attacked much more efficiently by bacteria. This was very controversial, as dispersants are pretty toxic and an immense quantity was involved. Still, it seemed to work, and much of the oil was broken down into 1-10 micrometer droplets. In fact, it started to raise fears that it was working TOO well, a microbial explosion depriving the ocean floor of oxygen and creating a huge dead zone. But this seems not to have happened, and in fact so far the prognosis is good.We´re not out of the woods yet, the oil could yet turn up in unwanted places, and chemical damage by detergents might yet, for instance, devastate the local tuna population. But there have been lessons learnt for next time - and there will be a next time.Kerr RA (2010). Gulf Oil Spill. A lot of oil on the loose, not so much to be found. Science (New York, N.Y.), 329 (5993), 734-5 PMID: 20705818http://www.sciencemag.org/cgi/content/full/sci;329/5993/734?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=oil biodegradation&searchid=1&FIRSTINDEX=0&sortspec=date&resourcetype=HWCITKintisch E (2010). Gulf Oil Spill. An audacious decision in crisis gets cautious praise. Science (New York, N.Y.), 329 (5993), 735-6 PMID: 20705819http://www.sciencemag.org/cgi/content/full/329/5993/735Vila, J., Nieto, J., Mertens, J., Springael, D., & Grifoll, M. (2010). Microbial community structure of a heavy fuel oil-degrading marine consortium: linking microbial dynamics with polycyclic aromatic hydrocarbon utilization FEMS Microbiology Ecology DOI: 10.1111/j.1574-6941.2010.00902.x* the oil "barrel" is actually based on a type of old English wine barrel or "teirce" holding 35 gallons.... Read more »

  • August 18, 2010
  • 11:22 AM
  • 51 views

Can Energy Sector Workers Serve as Influential Public Ambassadors?

by Matthew C. Nisbet in Age of Engagement

Earlier today, in response to Sheril Kirshenbaum’s query at Discover’s Intersection blog, I spotlighted the key influence of opinion-leaders on energy related behavior.  As a follow up, let’s take a look at a new study out this month, co-authored by John Besley, an assistant professor of Communication at the University of South Carolina (and a friend of mine from our doctoral studies together at Cornell.)
In the study appearing at the International Journal of Hydrogen Energy, Besley and his co-author surveyed individuals in the state of South Carolina working in the hydrogen energy sector, evaluating their potential to serve as opinion-leaders on the topic.  They reasoned that workers in the energy sector are passionate and knowledgeable, can they also serve as community connectors and go-betweens on the subject?  And if so, what kinds of resources should they be provided to be most effective?
I posed several questions to Besley in an email about the study and its relevance.  Below I have posted the questions and his replies.

What is an opinion-leader?
Opinion-leaders are the people we turn to in our own social circle when we’re trying to figure out what to think about something new. They’re the information junkies that you know will have an informed opinion about some subject that you’re just learning about. Opinion-leaders can be people with jobs that put them at the center of social life such as religious leaders or elected officials but they can also be the mother on the street who somehow seems to know everything about the local restaurants and schools. Pollsters, marketers, and political operatives have long known about the value of courting opinion-leaders. They’re the ones who do the best job showing off new electronic toys, selling Tupperware and hosting coffee fundraisers for up-and-coming politicians.
Why are opinion-leaders important to new technologies, specifically to hydrogen technology?
My sense is that people have some sort of mental image of what hydrogen energy is but it’s probably pretty vague. It’s also potentially wrong if what they think about is the Hindenburg or the explosions at the end of the James Bond movie Quantum of Solace. The truth is most of us have very limited contact with hydrogen or fuel cell (HFC) technologies. Unless I walk down to the engineering school here on campus, the only time I encounter HFC technologies is in media stories or when I see an occasional test vehicle on the street.
The idea of the current article was to find that small group of people – about 100 in South Carolina – who are working with hydrogen and fuel cell technology in their every day work and find out whether those people have been talking to people about their experiences and to find out what they have to say. My co-author, Shannon Baxter-Clemmons, is in charge of the South Carolina Hydrogen and Fuel Cell Alliance so she has an interest in figuring out whether these workers might be able to help spread the word about HFC technologies in their lives outside of work.
Why do you think science communication research until only recently has overlooked the central role of opinion-leaders?
There’s just so much to study and maybe it’s a lot more obvious to study the impact of regular news media on how people view the world. It makes sense to put a lot of focus there. However, as the field has gotten more sophisticated, I think we have come to (re)realize that to understand public opinion we need to get into the messy business of understanding people’s everyday talk. Studying opinion-leaders is one way to get a handle on what’s happening in those conversations. The media certainly play a part in the process but studying public opinion about technology (or any subject) without looking at personal conversations would be like studying retailing by studying advertising without studying what actually happens in the stores where people actually buy the products.
Do you think opinion-leaders are even more central in today's world of digital and social media?
They’ve probably always been important I just wonder now whether there’s more tools available for the opinion-leader to make their views known, whether it’s Tweeting, posting on Facebook, or writing a blog. There’s also the question of whether people’s social networks have expanded or somehow changed in structure. One thing I know from my own life is that, even though I’ve moved around a few times, it’s easier to stay in touch with people and I still sometimes turn to friends I don’t see very often for guidance. It’s an interesting question but it would be tough to study.
You describe issue-specific opinion-leaders and general opinion-leaders?  What's the difference? Why would the difference matter to a public engagement initiative surrounding an emerging technology such as hydrogen?
I think this is partly a question of how we go about measuring opinion-leadership but there’s also a substantive difference between the idea of someone who is generally out there giving advice and the idea of someone who is more focused on specific topics. There’s plenty of overlap between the two groups but for the current study we found that, to identify people willing to get out there and say positive things about hydrogen and fuel cell technology, issue-specific characteristics were more important.
Questions used to measure general opinion-leaders focus on things like the degree of agreement/disagreement with statements such as “I enjoy convincing others of my opinion” while issue specific leadership is measured using relative agreement/disagreement with statements such as “My friends often use me as a source of knowledge in discussions about HFC technology.”
What are the important questions that follow-up research in this area should examine?
This study looked at whether opinion-leaders existed within the hydrogen and fuel cell worker community and then explored what these people think about the technology. It turns out the people who say they like telling people about hydrogen and fuel cell technologies are also the ones who are already out there talking to people. The next question is really whether there’s room to help these people out so that they reach more people or to encourage them to focus on specific things.
Another question my co-author and I are hoping to be able to do is figure out what messages are most effective in getting people to think about HFC technology in a positive light. In other words, we want to know if technology proponents are better off emphasizing environmental arguments, economic arguments, national security arguments, or some maybe something else. The key is finding out what best resonates with specific audiences.
In what ways is this study useful to an organization, university, or company seeking to engage the public on hydrogen technology?
Opinion-leaders can be powerful voices in communities. Media campaigns don’t always reach very far into society. This also means that it makes sense to hold events like Science Cafés or other outreach events even if they only attract a small group of people. The kind of people who turn up for these things are probably the kinds of people who are telling others about what they heard, creating a potential multiplying effect for outreach efforts. As I noted above, however, there hasn’t been enough discussion about how to mobilize these voices in useful ways rather than just hoping that everything will work out.
One obvious question is to ask whether it’s ethical to try and shape these conversations but it’s important to remember is that you’re probably not the only source of information for opinion-leaders. By definition, opinion-leaders are pretty connected individuals so I think working with them puts an onus on communicators to be open, honest and well-reasoned. If you mess with these people, they’re going to tell people what a jerk or idiot you are just as surely as they would have passed along their positive impressions.

What do readers think? Can we harness the expertise and enthusiasm of energy sector workers to engage the wider public on energy issues and choices?
Citations:
... Read more »

  • August 14, 2010
  • 04:39 PM
  • 60 views

Enhanced paper reading and huge kinase complexes

by Nir London in Macromolecular Modeling Blog

About a year ago we reported of PLoS and Molsoft launching a new way of publishing structural biology related papers. A couple of days ago I've stumbled on one such paper, published in PLoS biology and decided to take the technology for a ride.



... Read more »

  • August 12, 2010
  • 06:00 PM
  • 65 views

Why are some urinary tract infections chronic?

by Greg Laden in Greg Laden's Blog

Chronic infection is, in a way, the new emerging infectious disease. Many pathogens are relatively tenacious when they infect elderly individuals or individuals who are otherwise not fully immunocompetent, and such individuals are, thanks to modern medical technology and practice, more common in the population. Resistant bacteria can cause chronic infection. It is interesting to see more research oriented specifically towards the problem of chronic infection as a problem in and of itself, and a paper just out by Hannan, Mysorekar, Hung, Isaacson-Schmit and Hultgren, in PLoS Pathogens, is an interesting and important example of one such research project. Read the rest of this post... | Read the comments on this post...... Read more »

Hanan, T.H., Mysorekar, I.U., Hung, C.S., Isaacson-Schmid, J.L., & Hultgren, S.J. (2010) Early Severe Inflammatory Responses to Uropathogenic E. coli Predispose to Chronic and Recurrent Urinary Tract Infection . PLoS Pathogens, 6(8). info:/10.1371/journal.ppat.1001042

  • August 12, 2010
  • 04:48 PM
  • 60 views

Toward a better agriculture… for everyone

by Anastasia B in Biofortified

A recent paper in PLoS concluded: we reject the organic-conventional dichotomy and emphasize that, in order to optimize environmental sustainability, individual tactics must be evaluated for their environmental impact in the context of an integrated approach, and that policy decisions must be based on empirical data and objective risk-benefit analysis, not arbitrary classifications. The paper was Choosing Organic Pesticides over Synthetic Pesticides May Not Effectively Mitigate Environmental Risk in Soybeans (full text) by Christine Bahlai Continue reading...... Read more »

  • August 11, 2010
  • 12:17 PM
  • 71 views

Diet and alcohol alter epigenetics of breast cancer and might predict severity of disease

by Sally Church in Pharma Strategy Blog

Recently, I chanced upon a paper in the PLoS Genetics journal by two research groups from Brown University and the University of California San Francisco. Their findings suggest that epigenetic changes to DNA in breast cancers are related to environmental...... Read more »

Christensen, B., Kelsey, K., Zheng, S., Houseman, E., Marsit, C., Wrensch, M., Wiemels, J., Nelson, H., Karagas, M., Kushi, L.... (2010) Breast Cancer DNA Methylation Profiles Are Associated with Tumor Size and Alcohol and Folate Intake. PLoS Genetics, 6(7). DOI: 10.1371/journal.pgen.1001043  

  • August 10, 2010
  • 06:47 PM
  • 56 views

Aggregate Proteins and Brain Aging: Interesting new findings

by Greg Laden in Greg Laden's Blog

Neurodegenerative diseases (i.e. Alzheimer's and Huntington's) often involves the formation of aggregates of proteins in a patients' brain, correlated with the process of degeneration. Some of these proteins are unique to the specific disease and others are commonly found in healthy individuals but also occur intertwined with the disease-linked types. Until now, these "common proteins" were thought to be an effect of sampling the tissues and were ignored as background. A new paper out today in PLoS Biology suggests, however, that these protein aggregates may be linked to aging. The main reason to think this is that they are found more widely (in a phyologenetic sense) than previously expected ... having been isolated in Caenorhabditis elegans, the laboratory classic roundworm model. And, in C. elegans, they seem to be linked to aging. Read the rest of this post... | Read the comments on this post...... Read more »

David, D., Ollikainen, N., Trinidad, J., Cary, M., Burlingame, A., & Kenyon, C. (2010) Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans. PLoS Biology, 8(8). DOI: 10.1371/journal.pbio.1000450  

  • August 9, 2010
  • 08:47 PM
  • 66 views

Lack of neutrality in bacteria and where pseudogenes go when they die

by Jonathan Eisen in The Tree of Life




Pseudogenes, which are in essence regions of the genome that used to be genes but no longer able to produce a functional unit, have long been considered to be models of the genetic equivalent of Switzerland's neutrality.  With this assumption of neutrality in hand, researchers have used studies of pseudogenes to better understand what happens to DNA when it is not visible to any form of natural selection.  That is, pseudogenes have been thought to be neither harmful (as in, they are not under negative selection) or helpful (i.e., they are not under positive selection).

And from this assumption we have supposedly learned about mutation rates and patterns (because if they are neutral then the changes in pseudogenes should be reflective of mutational processes, not selection) as well as all sorts of other features of genome evolution.
Over the years, some have challenged the assumption of neutrality of pseudogenes (e.g., see here) like many have questioned whether Switzerland is really neutral.  But overall, the feeling that pseudogenes were mostly neutral seems to have stuck.  However, that may change a bit with a new paper from Chih-Horng Chu and Howard Ochman in PLoS Genetics (PLoS Genetics: The Extinction Dynamics of Bacterial Pseudogenes).
In their paper they report: (this is their authors summary)Pseudogenes have traditionally been viewed as evolving in a strictly neutral manner. In bacteria, however, pseudogenes are deleted rapidly from genomes, suggesting that their presence is somehow deleterious. The distribution of pseudogenes among sequenced strains of Salmonella indicates that removal of many of these apparently functionless regions is attributable to their deleterious effects in cell fitness, suggesting that a sizeable fraction of pseudogenes are under selection.Basically, what they did was the following
1. Compare Salmonella genomes.  Identify putative pseudogenes and trace their evolution onto a phylogeny of the species.

 Figure 1. Distribution of pseudogenes among Salmonellagenomes.The phylogenetic tree was inferred from 2,898 single-copy genes shared by all fiveS. enterica subsp. enterica strains and the outgroup S. enterica subsp. arizonae.doi:10.1371/journal.pgen.1001050.g001

2. Carry out a variety of analyses of the pseudogenes such as looking at ratios of Ka/Ks (this is in essence a ratio of amino acid changes - aka non synonymous substitutions to "silent" synonymous changes which occur when the DNA sequence changes but the same amino acid is encoded).
examining the types and frequencies of gene inactivating mutations
3. Then they looked at the "ages" of pseudogenes - with age being estimated by the position in the tree in which the pseudogenes appear to have arise.  
4. Finally the examined the age class distribution of pseudogenes as well as whether there were other differences between pseudogenes of different ages.  And what they found was inconsistent with a neutral model.  Instead, what they conclude is that something is making it advantageous to delete pseudogenes more rapidly than one might expect.  
What explains this?  After testing multiple possibilities the authors conclude that their is some negative selection against pseudogenes (or I guess positive selection for deletion of pseudogenes).  
They conclude by suggesting this is likely to be pervasive across all bacteria and even in archaea.  And furthermore make a connection to possible selection on intron size in eukaryotes.  Anyway - the paper seems quite interesting and worth a read.  Still pondering what it all means, so I would welcome comments.
Kuo, C., & Ochman, H. (2010). The Extinction Dynamics of Bacterial Pseudogenes PLoS Genetics, 6 (8) DOI: 10.1371/journal.pgen.1001050
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This is from the "Tree of Life Blog"
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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  • August 4, 2010
  • 08:08 AM
  • 48 views

Endpoint of overfishing is now in sight: Firth of Clyde

by DeLene Beeland in Wild Muse

Seems like any time I read about ecology studies lately, its tales of waste and wanton destruction. And a recent paper in PLoS-One about “Ecological Meltdown in the Firth of Clyde, Scotland” was no different. Sigh. May as well have titled this post “Why we need Hands-Off conservation approaches.” The paper describes commercial fishing in the [...]... Read more »

  • August 3, 2010
  • 06:48 PM
  • 54 views

One fish, two fish

by Journal Watch Online in Journal Watch Online

The great count is nearing its end. Marine researchers have unveiled the first tidal wave of data from the Census of Marine Life, a decade-long effort to survey all sea life. The dozen papers, published by PLOS One, begin to detail the thousands of known species – from fish to flatworms — that live in […] Read More »... Read more »

  • August 3, 2010
  • 09:05 AM
  • 45 views

Double the mutualists, double the fun?

by Jeremy Yoder in Denim and Tweed

For all living things, information is critical to survival. Where's the best food source? Is there a predator nearby? Will this be a good place to build a nest? It probably shouldn't be surprising, then, that lots of animals do what humans do when faced with a host of hard-to-answer questions—they take their cues from their neighbors.

Red-backed shrikes place their nesting sites near where other shrike species have set up territories. Many bird species recognize each other's predator alarm calls, and respond appropriately. And a new natural history discovery published in the latest issue of The American Naturalist shows that treehoppers let one species of butterfly know where to find ants that will tend its larvae [$a].

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The ant-tended butterfly (Parrhasius polibetes, above) looks for ant-tended treehoppers (Guayaquila xiphias, below) to know where to lay her eggs. Photos from Kaminski et al. (2010), figure 2.The treehoppers help out the butterfly inadvertently, because both of them are dependent on a common resource: ants. Like many true bugs, treehoppers make their living sucking the sap of a host plant. This gives them a surplus of simple sugars and water, which they excrete as "honeydew" to attract ants for protection. As it happens, the larvae of the butterfly Parrhasius polibetes do the same thing—so the new study's authors hypothesized that P. polibetes females might prefer to lay their eggs on plants where treehoppers were already present, since those would likely already have ants ready to protect butterfly larvae.

To test this, the authors set up experimental pairs of host-plant branches, one occupied by ant-tended treehoppers, and one not. They excluded ants from accessing the unoccupied branch with Tanglefoot, a water-resistant glue used in insect traps. After 48 hours, they checked the experimental plants for newly-laid butterfly eggs, and found that P. polibetes was both more likely to lay eggs, and laid more eggs at a time, on branches occupied by treehoppers.

To assess the fitness benefit of laying eggs on treehopper-occupied plants, the authors compared the survival of newly hatched P. polibetes larvae artificially introduced onto branches occupied by treehoppers to the survival of larvae introduced to branches unoccupied by treehoppers (and with ants excluded, again, using Tanglefoot). The larvae placed with treehoppers had substantially better odds of survival—about six times better.

These two experiments confound the effect of treehoppers with the effect of ants, however—so the authors performed one additional experiment. In this one, they set up paired branches with and without treehoppers, but allowed ants to reach both the occupied and unoccupied branches—and the general result from the earlier experiment held. Larvae placed near treehoppers were three times more likely to survive for the duration of the experiment even when larvae placed on a branch without treehoppers were able to attract ants on their own.

So it looks like P. polibetes is able to freeload on the treehoppers' ant-attracting efforts, and benefits from that freeloading. What effect does that freeloading have on the treehoppers, or the ants, or the host plant? It's hard to say based on the data presented in the current paper, but I'd guess that the treehoppers don't lose much—in fact, they might gain from having another ant-attracting insect nearby, just as the butterfly larvae do. Similarly, it's probably helpful for the ants to have more honeydew-producing species in the same location. It's almost like that commercial for ... what was the product?



(I'll leave it to you, dear reader, to decide which insects correspond to which gendered pair in that video.)

I'd think, though, that this pile-on isn't so good for the host plant, if plants already hosting treehoppers are more likely to have to deal with butterfly larvae, too. Untangling all the different ways these four species—ants, treehoppers, butterflies, host plants—exert direct and indirect natural selection on each other should keep the authors busy for a long time to come.

References

Hromada, M., Antczak, M., Valone, T., & Tryjanowski, P. (2008). Settling decisions and heterospecific social information use in shrikes. PLoS ONE, 3 (12) DOI: 10.1371/journal.pone.0003930

Kaminski, L., Freitas, A., & Oliveira, P. (2010). Interaction between mutualisms: Ant‐tended butterflies exploit enemy‐free space provided by ant‐treehopper associations. The American Naturalist DOI: 10.1086/655427

Magrath, R., Pitcher, B., & Gardner, J. (2007). A mutual understanding? Interspecific responses by birds to each other's aerial alarm calls. Behavioral Ecology, 18 (5), 944-51 DOI: 10.1093/beheco/arm063
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  • August 2, 2010
  • 08:00 AM
  • 58 views

Pushing towards acknowledging sex differences in physiology and treatment efficacy

by EcoPhysioMichelle in C6-H12-O6

It is no surprise to many people that men and women are sometimes more susceptible to certain diseases than the other. By virtue of having differing anatomy, physiology, and gender expectations, we are going to be prone to different types of diseases, injuries, syndromes, and whatever-you-call-its. That being said, the majority of pathologies affect both men and women relatively equally. Despite that fact, rarely do clinical trials explore the difference in response to treatments based on sex. In 2008, Phyllis Greenberger wrote a letter to Science, Flaunting the Feminine Side of Research Studies, lamenting the fact that more studies didn't explore the effect of sex as a variable on treatment efficacy. To appropriately evaluate the success of women's representation in clinical trials, we must focus on the inclusion of women (and men) in studies of conditions that affect both sexes. Discussions of raw counts of overall research participation and inclusion of single-sex studies hide the fact that women's inclusion still lags in some key areas [...] Moreover, studies that include similar numbers of men and women rarely analyze or report the results by sex. This hampers our ability to understand the differences between men and women and to use this knowledge to improve health care outcomes.In response to this letter, Dr. Isis wrote a really excellent blog post detailing the complications involved in including women in cardiovascular clinical trials. Does Dr. Isis limit her research model because she secretly hates women (especially those hotter than her) and does not want to cure them?  No, but she appreciates that the effects of estrogen on vascular function are hugely complex and temporally based.  This stuff is so complex that people spend their careers studying it and there are all sorts of fancy books devoted to the topic.  In the human studies Dr. Isis has been/is involved with, we have to be careful to study women in the context of their menstrual cycle. [...] I could not agree more with Ms. Greenberger that the inclusion of women in clinical research is vital to the understanding of our unique physiology and I applaud her for reminding us of this public health disparity.  However, except in phase III or IV clinical trials where sample sizes may be sufficiently huge to allow for the inclusion of secondary endpoints and the splitting of populations for secondary analyses without devastating one's statistical power, splitting the populations of smaller, mechanistic studies can result in meaningless findings.There's no easy answer to this problem, especially in systems where the cycling of estrogen may be a confounding factor in treatment efficacy. Sex is not the only variable here, but also the levels of sex endocrines circulating through the system, which is dependent on each individual woman's place in her cycle at the time of treatment. Still, something has to be done, because not taking these variables into account can lead to a misleading conclusion about treatment efficacy.In Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review, published this month in PLoS ONE, Gartlehner et al. explored drug class reviews by the Drug Effectiveness Review Project to "determine whether clinically relevant differences in efficacy and safety exist between men and women when treated with commonly prescribed medications."[T]he exact differences between men and women at the genetic, cellular, or functional levels of the body are largely unknown. [...] Although differences in risks for and prognoses of several diseases have been well documented,, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. Variations in absorption, distribution, metabolism, and excretion of pharmaceuticals between men and women have been investigated and demonstrated for various drugs. [...] The majority of these findings indicate differences on physiological, pharmacodynamic, or pharmacokinetic outcomes and are mostly attributed to hormonal fluctuations. Whether such findings translate into clinically relevant differences in efficacy and safety of pharmacological treatments remains undetermined.Unsurprisingly, they could only find studies that explored the effect of sex on treatment efficacy on 23% of the medications listed in the drug class reviews. Of that subsection, most of the medications had no significant difference in treatment efficacy between men and women. One difference they did find was that women respond less favorably than men to a relatively new class of antiemetics (5-HT3 antagonists) used to treat nausea in chemotherapy patients.During chemotherapy, serotonin is released by certain epithelial cells in the digestive tract. This serotonin goes back to the brain and stimulates the vagus nerve, which feeds to the medullary vomiting center. The medullary vomiting center is pretty cool, it's this little corner of your brain with the sole purpose of deciding whether or not you should be vomiting at any given time. The serotonin released in response to chemotherapy says to your brain, "Hey, you need to vomit now," and then you do. These 5-HT3 antagonists block the receptor for serotonin, so the message isn't received by the medullary vomiting center, and you get to keep your breakfast. (Interestingly, these drugs don't seem to work in response to motion sickness, just chemical stimulation.)Unfortunately for women, there's pretty clear evidence that men are more likely to see a positive result from these antiemetics than women:(Click to enlarge)58% of men, compared to 45% of women, responded favorably to prophylactic treatment with this class of antiemetics prior to chemotherapy. The mechanism underlying why this happens is unknown, but this is clear evidence that even in systems that don't directly involve endocrine cycling, men and women can still display different responses to treatments. The authors also found that women are more likely to experience adverse effects from statin medications, and that men are more likely to experience sexual dysfunction from second-generation antidepressants than women. Bear in mind that these findings are based on less than 1/4th of the drug classes reviewed by the Drug Effectiveness Review Project, because the vast majority of studies didn't even consider sex differences as a variable in treatment efficacy! Incorporating the effect of sex and endocrine cycling can be problematic for an investigator, as Dr. Isis describes in her post linked above, but even still she realizes the importance of doing it anyway whenever possible. At the end of the day, men and women are different, physiologically speaking, and clinical trials that do not attempt to address this fact somewhere along the line of treatment development are doing us all a disservice.Greenberger, P. (2008). Flaunting the Feminine Side of Research Studies Science, 322 (5906), 1325-1326 DOI: 10.1126/science.322.5906.1325b... Read more »

  • August 2, 2010
  • 04:49 AM
  • 64 views

That's not a poker face, this is a poker face

by Christian Jarrett in BPS Research Digest

What does your poker face look like? If it's the traditional, stern, emotionless expression, you may want to consider practising a new one. Erik Schlicht and colleagues report that a friendly, trustworthy face is more likely to influence your opponents, leading them to think that you've got a good hand - that you're not bluffing.

Schlicht's team had 14 relative novices play hundreds of one-shot rounds of a simplified version of Texas Hold'em poker against hundreds of different 'opponents'. Each round the participants received a two-card hand and their opponent had bet 5000 chips. They had to decide whether to 'fold' or 'call'. Folding meant they would lose 100 chips guaranteed. By calling, they would win 5000 chips if their hand was stronger then their opponent's, or lose the same amount if their hand was weaker.

Each round, before making their decision, the participants saw a picture of their opponent's face. These were morphed to appear either untrustworthy, neutral or trustworthy (see picture). Participants were told that, as in real poker, the different opponents could have different styles of play (but no mention was made of faces providing a clue to style).

Because participants played just one round against each opponent there was no opportunity to use past behaviour to make judgments about their style. This meant the only information participants had to go on was the cards in their own hand and any inferences they'd made about their current opponent's playing style based on his face. They didn't receive any feedback during play on whether they'd won a round or not.

On each round, there was an optimal decision for participants to make considering the cards in their hand and the stakes involved in holding or calling. The researchers were careful to ensure that participants' hands were of equal value across the different categories of opponent face - trustworthy, neutral, untrustworthy. Unbeknown to the participants, their opponents' hands bore no relation to their facial expression.

The key finding was that faces with neutral or untrustworthy expressions made no difference to the decisions the participants made. By contrast, if an opponent had a trustworthy face, the participants took longer to decide what to do and they made less optimal decisions. Effectively, they were behaving as if their opponent had a better hand.

'Contrary to the popular belief that the optimal face is neutral in appearance,' the researchers said, 'poker players who bluff frequently may actually benefit from appearing trustworthy, since the natural tendency seems to be inferring that a trustworthy-looking player bluffs less.' Before you try this out at your local poker den, remember the findings apply when you're up against new opposition and there's little other information to go on.
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Schlicht EJ, Shimojo S, Camerer CF, Battaglia P, & Nakayama K (2010). Human wagering behavior depends on opponents' faces. PloS one, 5 (7) PMID: 20657772




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Schlicht EJ, Shimojo S, Camerer CF, Battaglia P, & Nakayama K. (2010) Human wagering behavior depends on opponents' faces. PloS one, 5(7). PMID: 20657772  

  • July 30, 2010
  • 03:30 PM
  • 99 views

Koreans, not quite the purest race?

by Razib Khan in Gene Expression

PLoS One has a paper out on Korean (South) population genetics and phylogeography, Gene Flow between the Korean Peninsula and Its Neighboring Countries:
SNP markers provide the primary data for population structure analysis. In this study, we employed whole-genome autosomal SNPs as a marker set (54,836 SNP markers) and tested their possible effects on genetic ancestry [...]... Read more »

Jung J0, Kang H, Cho YS, Oh JH, & Ryu MH. (2010) Gene Flow between the Korean Peninsula and Its Neighboring Countries. PLoS ONE. info:/10.1371/journal.pone.0011855

  • July 30, 2010
  • 07:42 AM
  • 95 views

Not the bang they were looking for

by Niall in we are all in the gutter

A satellite detects a bright burst of gamma-rays. Within minutes telescopes swing in to action expecting to see a massive star being torn apart by a cataclysmic explosion in a far-flung corner of the universe. But that wasn't what they found........... Read more »

Rachel A. Osten, Olivier Godet, Stephen Drake, Jack Tueller, Jay Cummings, Hans Krimm, John Pye, Valentin Pal'shin, Sergei Golenetskii, Fabio Reale.... (2010) The Mouse that Roared: A Superflare from the dMe Flare Star EV Lac detected by Swift and Konus-Wind. Accepted for publication in the Astrophysical Journal. arXiv: 1007.5300v1

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