Post List

  • June 25, 2011
  • 04:30 PM
  • 2,918 views

Harry Potter and Corynebacterium

by Pranab Chatterjee in Scepticemia

How does Harry Potter and Corynebacterium toxins find a connecting bridge?... Read more »

A. M. Pappenheimer, Jr. (1942) Studies on Diphtheria Toxin and Its Reaction with Antitoxin. J Bacteriol., 43(3), 273-289. info:/

  • June 25, 2011
  • 04:25 PM
  • 1,355 views

World’s Oldest Rock Symbols?

by Cris Campbell in Genealogy of Religion

The holy grail of archaeology is to discover the earliest evidence of symbolic thought in humans. Generally speaking, symbolism means that one thing represents or stands for another. In its most basic form, symbolic thought is iconic: an object in the world (e.g., rock) is related to an idea in the mind (e.g., person).
Because this [...]... Read more »

Bednarik, R. (2003) A Figurine from the African Acheulian. Current Anthropology, 44(3), 405-413. DOI: 10.1086/374900  

d'Errico, Francesco, & Nowell, April. (2000) A New Look at the Berekhat Ram Figurine: Implications for the Origins of Symbolism. Cambridge Archaeological Journal, 123-167. info:/10.1017/S0959774300000056

  • June 25, 2011
  • 04:22 PM
  • 1,856 views

Terrestrialisation

by Marc in Teaching Biology

For PDFs of this entire talk series, click here! [17.62MB rar file with 6 PDFs] Due to the inherent time constraints of having to compress what is usually a semester’s worth of knowledge into 4.5 hours, we will now move away from the oceans permanently and look at the rest of the history of life [...]... Read more »

  • June 25, 2011
  • 12:14 PM
  • 2,251 views

Can we use viruses to vaccinate against - and cure - established cancers?

by Connor Bamford in The Rule of 6ix

Everyone is aware of the ability of our immune system to defend against microbial pathogens yet its role in the prevention of other diseases - like cancer - is generally over-looked. Yet it is through the harnessing of our immune system that novel ways of combating cancer may arise. And interestingly enough, through the use of engineered viruses - the same ones our immune system protects against - we may now control aspects of immunity to suit these medical needs. Kotke et al, report in Nature Medicine just this week, their use of a new virus-based immunotherapy platform that was able to effectively 'cure' mice suffering with cancer.

One of the hallmarks of cancer appears to be the ability to persist in the face of an active immune system - see fig. 1. Newly cancerous cells and tumours are able to survive and proliferate without - or at least protecting themselves - against a full-blown immune attack. Our immune system is usually able to protect us from the development of cancer but in some cases something fails and the result is more often than not - cancer.



Fig 1. Newly recognised cancer hallmarks - note avoiding immune destruction. (Hanahan and Weinberg 2011).


Through the recognition of 'tumour antigens' (proteins expressed only on cancer cells) or 'tumour-associated antigens' (proteins expressed differently on cancer cells), our immune system is usually able to mount an effective response toward those cells. This is the  system that tumours are able to suppress yet we may be able to boost the natural immunological nature of tumours in order to cure them. The discovery of these proteins - just like those found on the surface of virus particles or bacterial cells - may allow us to effectively vaccinate people against cancer, allowing their own immune system to remove the cancerous cells.

This is what we try and achieve through cancer vaccines and immunotherapies. Kotke et al set about trying to improve upon these current immunotherapy platforms, which - as they state - suffered from a number of problems including: lack of known tumour antigens and coverage of only a few such proteins. Most current immunotherapies rely upon the immunization with only a single antigen. Previous work by the group showed that if you kill normal cells from a patient in vivo - you may be able to elicit an effective anti-tumour immune response through the induction of tumour-associated antigen immunity (when cells die they either burst and release their insides).This work effectively showed that you could immunize with a wide range of tumour-associated antigens from normal cells and protect against cancer - both circumventing the above two problems.





VSV particles - www.standford.edu
To improve upon this model, they developed a virus-based platform for the expression of a wide range of tumour-associated antigens in vivo termed altered self antigen and epitope library (ASEL) - see fig 3. They based their method upon the vesicular stromatitis virus - or VSV - normally a virus solely of livestock that also has the ability to infect humans. In humans it causes a generally mild flu-like illness and may form vesicles on the skin. Although a single-stranded non-segmented negative sense RNA virus, we have the ability to generate infectious VSV particles entirely from cDNA plasmids encoding the entire VSV genome. This has facilitated the development of VSV as a key eukaryotic expression vector for multiple uses, such as these cancer immunotherapies and specifically, as an oncolytic treatment. Using standard molecular biology techniques (PCR, restriction enzyme digests and ligations) you can insert any gene from whatever source you want into the VSV genome and it will be expressed inside cells following infection. The benefit with using this virus is that even without the expression of tumour antigens from it's genome, replication within a cell will kill the cell anyway. It is a double hit strategy.



Fig.3. Cloning the cDNA library into the VSV genome in forward and reverse orientations = VSV-ASEL library

In order to express hundreds of tumour-associated antigen genes, the group used reverse-transcriptase PCR to amplify all expressed genes from normal prostate tissue and inserted the entire normal prostate tissue cDNA library into VSV. They were then able to infect mice that suffered with prostate cancer and observe what happened to their tumours - specifcally, was an effective immune response generated and did the tumour shrink? VSV virus particles were injected into the mice, virus entered the cells of the mice and began to replicate and express their genes, including the newly inserted prostate cDNA. Essentially, thousands of virus particles were adminsired, each containing a slightly different gene from the prostate cDNA library. High levels of tumour associated antigens were therfore being expressed in mice allowing for the generation of an effective immune response.



Survival of mice treated with the VSV viruses - GFP expressing negative control; and the VSV ASEL in mice with established 'TC2' prostate tumours.

This approached effectively cured the mice who suffered from prostate cancer. Following this treatment a number of resistant tumours emerged which were again subjected to a further treatment using a cDNA library taken from the tumour itself this time and this readily treated the secondary resistant cancers. The clinical benefits of this approach can hardly go unnoticed. The ability to administer a broad tailored therapy that has the potential to cure an established tumour will be revolutionary, especially given the relative ease at which this can be developed 'at the bedside'. The ability to easily genetically manipulate viruses has - and will continue to - revolutionise the medical sciences. Look out for the eminent clinical trials. 


... Read more »

Kottke, T., Errington, F., Pulido, J., Galivo, F., Thompson, J., Wongthida, P., Diaz, R., Chong, H., Ilett, E., Chester, J.... (2011) Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors. Nature Medicine. DOI: 10.1038/nm.2390  

  • June 25, 2011
  • 10:50 AM
  • 1,918 views

The National Children's Study: A view from across the pond

by Dorothy Bishop in bishopblog

Vast amounts of US research funds have gone to support the National Children's Study, a longitudinal cohort study of 100,000 families. At a time of financial stringency, I ask whether this is a good use of funds, and query why cohort studies are so much more expensive in the US than in Europe... Read more »

Magnus, P., Irgens, L., Haug, K., Nystad, W., Skjaerven, R., Stoltenberg, C., & , . (2006) Cohort profile: The Norwegian Mother and Child Cohort Study (MoBa). International Journal of Epidemiology, 35(5), 1146-1150. DOI: 10.1093/ije/dyl170  

Olsen, J., Melbye, M., Olsen, S., Sorensen, T., Aaby, P., Nybo Andersen, A., Taxbol, D., Hansen, K., Juhl, M., Schow, T.... (2001) The Danish National Birth Cohort - its background, structure and aim. Scandinavian Journal of Public Health, 29(4), 300-307. DOI: 10.1177/14034948010290040201  

Savitz, D., & Ness, R. (2010) Saving the National Childrenʼs Study. Epidemiology, 21(5), 598-601. DOI: 10.1097/EDE.0b013e3181e942cc  

  • June 24, 2011
  • 08:54 PM
  • 1,525 views

Happy Belated Father's Day

by Jon Wilkins in Lost in Transcription

So, Farther's day was almost a week ago, but I wanted to share this video, which illustrates all the good-timey ho-down fun that led to your father becoming your father.

Did I just call your mom a ho?  It sure seems like it, doesn't it?



If you want to try this (or something like it) at home, check out the ideas in this article:

Joseph P. Chinnici,, Joyce W. Yue,, & Kieron M. Torres (2004). Students as “Human Chromosomes” in Role-Playing Mitosis & Meiosis The American Biology Teacher, 66 (1), 35-39

... Read more »

Joseph P. Chinnici,, Joyce W. Yue,, & Kieron M. Torres. (2004) Students as “Human Chromosomes” in Role-Playing Mitosis . The American Biology Teacher, 66(1), 35-39. info:/

  • June 24, 2011
  • 08:37 PM
  • 1,925 views

Screening for autism in infants and toddlers

by Jon Brock in Cracking the Enigma

It’s widely believed that early intervention is crucial for long-term prognosis in autism and that the earlier the intervention begins the better. Getting in early, of course, requires that autistic children are identified at a young age. But even for more severe forms of autism, children are rarely diagnosed before three to four years of age. With this in mind, the American Academy of Pediatrics has recommended screening all toddlers for autism.However, writing in next July’s issue of Pediatrics (the academy’s own journal), Mona Al Qabandi and colleagues argue against routine population-based screening for autism. Chief amongst their objections is that existing screening tools are simply not up to the task. Most of these screens involve a questionnaire given to parents, sometimes augmented with a brief phone interview. But they all have their problems. Some are insensitive, missing a large number of kids who go on to get an ASD diagnosis further down the line. Others are sensitive but not specific, hoovering up all kinds of kids, many of whom don’t have autism, and may not have any kind of developmental problems at all.Al Qabandi et al. conclude that “none of the autism screening tests currently available has been shown to be able to fulfill the properties of accuracy… in a population-wide screening program”.Similar conclusions were reached in an earlier review by Josephine Barbaro and Cheryl Dissanayake at the Olga Tennison Autism Research Centre in Melbourne. So they tried a different approach. Rather than relying on parental questionnaires, they set up a 'surveillance program', training community nurses to spot the signs of autism during regular infant health checks.Each nurse attended a short two-and-a-half-hour workshop in which they were shown how to complete the screen. They were given a checklist with key behaviours to monitor, depending on the child’s age, and were trained how to score each item as either typical, atypical, or absent. For instance, the item for “eye contact” read as follows:"Has the child spontaneously made eye contact with you during the session? If not, interact with the child to elicit eye contact. Does s/he make eye contact with you?"From an initial sample of almost 21 thousand children, 216 were identified as “at risk” of ASD by 24 months of age. Of these, 110 completed further assessment, including the ADOS and ADI-R. 89 of these kids received an ASD diagnosis, giving the surveillance program a positive predictive value of 81%. Of the remaining 21 children, all but one had developmental language disorders.Calculating the screening program’s sensitivity is an inexact process at this stage. But assuming that the rates were similar for the children who did not undergo further assessment, Barbaro and Dissanayake estimated that approximately 175 ASD children would have been picked up. Dividing this by the total number of kids in the program gave an estimated prevalence of 1 in 119. This is reassuringly close to recent estimates of approximately 1 in 100 kids having an ASD, suggesting that the screen managed to pick up the majority of ASD kids in the initial sample.To get a more accurate indication of sensitivity, however, the researchers will have to wait until the children enter school. Only then will they be able to work out how many children end up with an ASD diagnosis but weren’t picked up by the screening measure.While it’s still early days, the Melbourne study suggests that population-wide screening for autism is possible, at least in areas that already have comprehensive child health checks. References:Barbaro, J., & Dissanayake, C. (2010). Prospective Identification of Autism Spectrum Disorders in Infancy and Toddlerhood Using Developmental Surveillance: The Social Attention and Communication Study Journal of Developmental & Behavioral Pediatrics, 31 (5), 376-385 DOI: 10.1097/DBP.0b013e3181df7f3cAl-Qabandi M, Gorter JW, & Rosenbaum P (2011). Early Autism Detection: Are We Ready for Routine Screening? Pediatrics PMID: 21669896Links:Olga Tennison Autism Research CentreFurther reading:Irresponsible Pediatrics article argues against autism screeningNot ready for introduction of routine screening for autism? Clarifying the issuesThe case against caution... Read more »

  • June 24, 2011
  • 07:25 PM
  • 2,829 views

No door? No problem. T. cruzi uses the window to cause Chagas Disease

by James Byrne in Disease Prone

For invasive pathogens the only way to survive, and consequently make you sick, is to get inside your cells. This is a rough exercise as you have an immune system working everywhere in the body to prevent this and the cell to be invaded is none too happy with the idea either so invasive pathogens must use tricks.... Read more »

Jermy A. (2011) Parasitology: Adding insult to injury. Nature reviews. Microbiology, 9(7), 484. PMID: 21625249  

  • June 24, 2011
  • 04:51 PM
  • 1,295 views

Are Grouper Eating Invasive Lionfish?

by Sam in Oceanographer's Choice

A short but provocative study just came out in the open-access journal PLoS ONE. As readers may or may not be aware, the Caribbean Sea has seen an invasion of lionfish over the past five to ten years. No one … Continue reading →... Read more »

Peter J. Mumby, Alastair R. Harborne, Daniel R. Brumbaugh. (2011) Grouper as a Natural Biocontrol of Invasive Lionfish. PLoS ONE, 6(6). info:/doi:10.1371/journal.pone.0021510

  • June 24, 2011
  • 04:45 PM
  • 1,584 views

Buzzing bees in poppies

by Africa Gomez in BugBlog

There were lots of poppies around today, and they buzzed with a high pitch produced by the bees and bumblebees inside, often more than one, gathering their almost black pollen. Poppies are unusual flowers, bright red, bowl shaped, with black centers and radial symmetry, and they do not produce nectar, just lots and lots of edible, protein-rich pollen. Poppies open at dawn, and before they do, their anthers start to release pollen. By the following day, fully fertilised and depleted of pollen, the flower loses its petals. Although the red and black colour combination of poppies - like some tulips and other Mediterranean flowers - is through to have evolved to be fertilised by beetles, bees and bumblebees take advantage of the pollen bonanza offered by these short-lived flowers. Bumblebees do not need much time to learn how to collect nectar, even from complex flowers, but pollen collecting is much trickier. The powdery pollen needs to be released from the anthers, brushed from the bees hairy body, mixed with nectar to make it sticky, packed into pellets and fixed to their corbicula, the specialized area on their legs adapted to carry the pollen. Nigel Raine and Lars Chittka, from Queen Mary University of London, carried out some experiments in a greenhouse to investigate how bumblebees learn to collect pollen. They used freshly collected poppy flowers from a field nearby before each bumblebee foraging trip, and tested six Bombus terrestris bumblebees that had never collected pollen before.The figure above shows how pollen from the wild collected poppies drastically decreased along the morning - as the wild bees outside collected it - by 9:00 am there wasn't much left. The researchers then computed the rate at which their bumblebees collected pollen from the poppies, related to the available pollen at each foraging bout, by removing and counting one of the pollen pellets brough to the colony after each foraging trip by each bee. Bumblebee pollen collection behaviour markedly changed with experience:During their first few visits, all bees were surprisingly clumsy, one bee even failed to collect any pollen during its first foraging bout despite making 56 flower visits. In the early stages of their foraging career, bees were observed to collect pollen loads that fell apart, or were so large that they fell from the bee’s corbiculae (pollen baskets) before reaching the nest. As each bee gained foraging experience, the frequency of such events rapidly declined. Bees also changed how they used ‘buzzing’, a technique of holding the anthers in their mandibles while vibrating their flight muscles, to facilitate pollen collection. While naïve bees typically buzzed either all or no flowers, skilled foragers would selectively ‘buzz’ flowers containing less pollen.The following graph shows how foraging efficiency increases with foraging trip, indicating that bees learn to be more adept at collecting pollen. Despite this, the bees seemed to forget most of what they had learn overnight, as efficiency was much lower in the first trip of the second day than in the last trip of the previous day. : A honeybee and a bumblebee share an Opium poppyReferencesRaine, N., & Chittka, L. (2006). Pollen foraging: learning a complex motor skill by bumblebees (Bombus terrestris) Naturwissenschaften, 94 (6), 459-464. DOI: 10.1007/s00114-006-0184-0Dafni, A.; Bernhardt, P., Shmida, A., Ivri, Y. and Greenbaum, S. (1990). Red bowl-shaped flowers: convergence for beetle pollination in the Mediterranean region. Israel Journal of Botany, 39, no1-2, pp. 81-92, 81-92 Other: 0021-213X... Read more »

DAFNI A.; BERNHARDT P., SHMIDA A., IVRI Y., GREENBAUM S. (1990) Red bowl-shaped flowers: convergence for beetle pollination in the Mediterranean region. Israel Journal of Botany , 39, no1-2, pp. 81-92(1-2), 81-92. info:other/0021-213X

  • June 24, 2011
  • 02:15 PM
  • 1,636 views

Drug Delivery with Dendrimers

by KJHaxton in Endless Possibilities v3.0

  A significant number of promising pharmaceuticals are organic molecules with painfully low solubility in water.  As most routes of drug administration involve aqueous substances such as blood, this is a big problem.  Drug delivery research focusses on effective delivery of such pharmaceuticals to improve the treatment regime for the patient or to [...]... Read more »

  • June 24, 2011
  • 01:31 PM
  • 1,458 views

Friday Fun: It's just a lamp

by Psych Your Mind in Psych Your Mind

I watched this IKEA commercial in my intro social psych class, and five plus years later, it is still seared into my memory. Take the minute to turn on your volume and watch this commercial, and then after the jump I'll tell you how Spike Jonze used social psychology to render me near tears.




Read More->... Read more »

Delbaere, M., McQuarrie, E., & Phillips, B. (2011) Personification in Advertising. Journal of Advertising, 40(1), 121-130. DOI: 10.2753/JOA0091-3367400108  

  • June 24, 2011
  • 01:18 PM
  • 4,273 views

When a tree falls in a stream, there’s always something around to make use of it.

by Chris Rowan in Highly Allochthonous

Allochthonous may have some obscure usage related to rocks, but in ecology, allochthonous material is a major concept that underpins thinking about nutrient cycling and food web dynamics. In its most general definition, allochthonous material is something imported into an … Continue reading →... Read more »

Vannote, R., Minshall, G., Cummins, K., Sedell, J., & Cushing, C. (1980) The River Continuum Concept. Canadian Journal of Fisheries and Aquatic Sciences, 37(1), 130-137. DOI: 10.1139/f80-017  

  • June 24, 2011
  • 11:46 AM
  • 2,047 views

Subgenus Megapomys: Biogeography and the authors’ concluding remarks

by nath in Imprints of Philippine Science

Where are the Megapomys?... Read more »

  • June 24, 2011
  • 11:15 AM
  • 847 views

Subgenus Megapomys: Biogeography and the authors’ concluding remarks

by nath in Imprints of Philippine Science

The genus Apomys (Philippine forest mice) is proposed to be divided into two subgenera: Apomys and Megapomys based on the findings of the Heaney expedition [1]. Megapomys includes A. abrae, A. datae, A. gracilirostris, A.sacobianus, A. aurorae, A. banahao, A. brownorum, A. magnus, A minganensis, A. sierrae, and A. zambalensis. See previous post. The discovery isn’t serendipitous.  The authors used predictive biogeographic models that are [...]... Read more »

  • June 24, 2011
  • 11:05 AM
  • 2,403 views

A complex picture on marathoning and heart disease

by Dave Munger in Science-Based Running

Jim Fixx was an overnight sensation as a recreational runner who had worked himself into shape and written a book about the health benefits of running. But when he died of a heart attack shortly after a run at age 43, he became the poster-child for the idea that running can actually be hazardous to [...]... Read more »

Breuckmann, F., Mohlenkamp, S., Nassenstein, K., Lehmann, N., Ladd, S., Schmermund, A., Sievers, B., Schlosser, T., Jockel, K., Heusch, G.... (2009) Myocardial Late Gadolinium Enhancement: Prevalence, Pattern, and Prognostic Relevance in Marathon Runners1. Radiology, 251(1), 50-57. DOI: 10.1148/radiol.2511081118  

  • June 24, 2011
  • 10:03 AM
  • 2,075 views

A tale of two hormone receptors – could prostate cancer therapy help breast cancer patients?

by Cancer Research UK in Cancer Research UK - Science Update

Breast cancer survival is one of the big success stories of recent years. Thanks to improvements in screening and treatment more than 70 per cent of women now survive for more than ten years, compared to around 40 per cent back in the 1970s. But while this is cause for celebration, the statistics hide the [...]... Read more »

Robinson J, MacArthur S, Ross-Innes CS, Tilley WD, Neal DE, Mills IG, & Carroll JS. (2011) Androgen receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. EMBO Journal. info:/

  • June 24, 2011
  • 09:10 AM
  • 1,425 views

What does it feel like to get bitten by a ground hornbill, I hear you ask?

by Darren Naish in Tetrapod Zoology



Suppose you're interested in the anatomy and biology of ground hornbills. Now suppose that you get the chance to make physical contact with one of these awesome birds. Here, at least, is the opportunity to get bitten!! Surely you've always wanted to know what it feels like when a ground hornbill bites you. No? Ok, maybe it's just me. Anyway, the opportunity to get bitten by a ground hornbill presented itself to me a few weeks ago, so who was I to miss out? Read the rest of this post... | Read the comments on this post...... Read more »

van der Meij, M., & Bout, R. G. (2004) Scaling of jaw muscle size and maximal bite force in finches. Journal of Experimental Biology, 207(16), 2745-2753. DOI: 10.1242/jeb.01091  

  • June 24, 2011
  • 08:58 AM
  • 2,092 views

The Great Atlantic Divide – Why Europeans Riot (but American’s don’t)

by Stuart Farrimond in Dr Stu's Science Blog

A fireball erupts as civilians shriek and run for cover. A security officer burns and a gas mask-wearing man dashes through the smoke. Men beat each another with bats and stones. Shots are fired and grenades hurled as a city centre descends into chaos. Is this a scene from a warzone? No – this is … Continue reading »... Read more »

Alesina, A., Di Tella, R., & MacCulloch, R. (2004) Inequality and happiness: are Europeans and Americans different?. Journal of Public Economics, 88(9-10), 2009-2042. DOI: 10.1016/j.jpubeco.2003.07.006  

  • June 24, 2011
  • 08:00 AM
  • 1,855 views

Give ‘em the old razzle dazzle, and give it to ’em fast

by Zen Faulkes in NeuroDojo

Why do zebras look like this?


You know. All stripey.

One theory for this “Notice me!” pattern was picked up by naval officials: that the complicated, high contrast shapes somehow made zebras harder to see. Here, we see the HMAS Australia, painted with “dazzle” colouration.


Some said this particular pattern contained a “lady’s leg.” But then, some people see that sort of thing everywhere.

That the advantage of this kind of pattern hasn’t been well tested is maybe not surprising. “Hard to see” is a wide and ill-defined term that could be measured in a lot of ways.

Scott-Samuel and colleagues examined this by showing images with patterns on a computer screen. Their subjects were show two moving blocks, and had to judge which of the two were moving faster. The “dazzle” patterns they used are shown here. They also used a plain white square as a standard to which everything else was compared.

When the patterns moved quickly against a high contrast background, people judged them to be moving slower than the plain white stimulus. Zigzags and checked patterns caused a larger effect (that is, were seen as moving slower) than those with stripes.

How fast do you have to be moving to get this effect? The authors estimate that the tested speeds on the computer screen are equivalent to 13 kilometers an hour for an object about 10 meters away. This is certainly within the range of biological capabilities. I found one site that estimated zebras can run at about 60 kilometers per hour. If a predator thinks an animal is running slower than it is, it could miss what it aims at.

That this effect works with humans doesn’t mean that it will work with other animals, however. For that matter, the effect might be enhanced for other kinds of animals. Different eyes, different possibilities.
It seems to me that this should be possible to test with animals. If you could train a visual predator to get a food reward for striking at a moving target, you would predict that the predator would miss targets with the dazzle patterns more often.

The authors take a more applied view. They do some calculations for a Land Rover under rocket attack. They reckon that the effect of dazzle colouration could be enough for someone to miss the vehicle is they were launching a rocket propelled grenade at it. Sadly, the paper contains no experimental test of this prediction.

Jeeps? Rockets? Now there’s a scientific prediction that has MythBusters written all over it.




Reference

Scott-Samuel N, Baddeley R, Palmer C, Cuthill I. 2011. Dazzle camouflage affects speed perception. PLoS ONE 6(6): e20233. DOI: 10.1371/journal.pone.0020233

Zebra photo by alles-schlumpf on Flickr; ship photo by ; both used under a Creative Commons license.... Read more »

Scott-Samuel N, Baddeley R, Palmer C, & Cuthill I. (2011) Dazzle camouflage affects speed perception. PLoS ONE, 6(6). DOI: 10.1371/journal.pone.0020233  

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