- October 8, 2009
- 09:58 PM
- 732 views
Another Method of Increasing Autophagy to Enhance Longevity
by Reason in Fight Aging!
Autophagy seems to be the topic of the week, and here's another example of research demonstrating enhanced longevity in laboratory animals through increased autophagy: Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice [and] led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Those of you who like your research a little more preprocessed than the original papers will no doubt prefer this article from the science press: It seems that spermidine exerts its influence at the level of the cell's mechanism for dealing with damaged internal components. Throughout a cell's life, proteins and other molecules become damaged by exposure to environmental factors such as UV light or oxidants. This debris is swept up and deposited into a biochemical recycling bin. However, as cells age this clean-up process, called autophagy, becomes less efficient and ultimately the accumulation of this waste causes the cell to trigger its own suicide. Autophagy is ultimately controlled by genes being switched on and off. It...... Read more »
Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L.... (2009) Induction of autophagy by spermidine promotes longevity. Nature Cell Biology. DOI: 10.1038/ncb1975
- October 8, 2009
- 08:07 PM
- 1,504 views
Women to stop liking Sean Connery?
by Christie Wilcox in Observations of a Nerd
Boyish good looks - the next generation of sexy?I couldn't help but notice that a new study has come out about the behavioral effects of hormonal contraception. It's all over the science news sites. With titles ranging from the conservative "Pill May Change Attraction" to the bolder "Taking the pill for past 40 years 'has put women off masculine men'"and "The pill 'gives women a taste for boyish men like Zac Efron'," this new publication has swept the media outlets by storm. This idea that birth control might have behavioral side effects isn't new, even I've mentioned this before, as a side note on another study's findings. But the strong tone and conclusions in this review paper seem to have caught the media's attention, causing Grizzly Adams impersonators everywhere to fear that they're soon to be cast out of their lovers' bedrooms in favor of DiCaprio-esque alternatives.Calm down, manly men. It's just like how the media always starts raving about how scientists have found a "missing link" every time there's a new fossil species identified - mention sex or relationships in a paper, and it's bound to get noticed. And just like the constant "missing link" hype, the whirlwhind response to this paper is unfounded and ridiculous.Don't get me wrong - I love a good paper about behavior and hormones. But a non-systematic review paper has a lot of holes in it, and this one is no exception.In the paper, the authors state that "there is emerging evidence that the use of the pill by women can disrupt: (i) the variation in mate preferences across their menstrual cycle; (ii) their attractiveness to men; and (iii) their ability to compete with normally cycling women for access to mates" and that there are "consequences of pill-induced choice of otherwise less-preferred partners for relationship satisfaction, durability and, ultimately, reproductive outcomes."Let me start by explaining the paper's premise. It's somewhat established scientifically that certain traits that women find attractive - like "manliness" - can vary over the menstrual cycle. When a woman is most fertile, she's more strongly attracted to more masculine men. There's some suggestion that this is because while she may not be able to marry the sexiest, most genetically spectacular man alive, she can sleep with him behind her mate's back when she's highly fertile and get a genetically fantastic kid while still keeping the loser hubby around to take care of him. In turn, scientists have shown that women are sexiest to men when they're most fertile - the theory being that if men sleep with a woman when she is most likely to get pregnant, then they're most likely to pass on their genes. All of these shifts in attractiveness are completely unconscious, so we don't know that we're changing how we see each other over a monthly cycle.The Culprit?Hormonal birth controls change the hormones in a woman's cycle. They convince her body that she's pregnant, thus preventing her from going through ovulation-induced changes into that 'high fertility' state. Logically following, this change in hormones might shift how she views men and how men view her, because she's never entering that body phase where all this change in attraction occurs. Then, the paper's authors conclude, it's likely that the women taking the pill are shifting society's opinion of men, steering towards less masculinity. They're changing the rules, making feminine men more attractive and thus more likely to mate, which they say could have drastic consequences. Since manly men are supposed to contain the 'better' genes, a shift in mate choice could have reproductive repercussions. As one of the co-authors, Dr Virpi Lumma, is quoted as saying: "The ultimate outstanding evolutionary question concerns whether the use of oral contraceptives when making mating decisions can have long-term consequences on the ability of couples to reproduce." Even on the small scale, they warn that birth control might be dooming relationships, because women are likely to be off birth control before a relationship, then meet someone, and go on it. Beforehand, the women had 'high fertility' attractions, but after, their tastes change. Even if it's not dooming the masses, it could be a major contributing factor to the rising divorce rate and general relationship woes.It sounds very logical, but there are gaping holes that the journalists and even the study authors completely ignore.Firstly, it's important to point out that this is a non-systemic review. A non-systemic review is one that doesn't describe the methods used to choose the papers which are included in it. The authors say that 75% of the studies performed in the past decade support their conclusions. But how did they choose the 72 studies included in their review? How exhaustive was their search? Without explaining these methods, it's entirely possible that the review is biased, focusing on research which supports the writers' preformed conclusion. Small, non-random samples aren't fit mathematically to be expanded to populationsBut even assuming that the choices were comprehensive when it comes to the literature, there are flaws in those, too. Most of these studies have incredibly low, non-random sample sizes (i.e. Furthermore, when comparing women who are on the pill to those who are not, the treatment group the women are in isn't double blind or random. The two groups are self selected - aka women who are on the pill already versus those that aren't. There is no control, no group that takes a placebo or, at least, goes from not taking the pill to taking it (with one exception - kind of. I'll explain in a minute). No clinical studies into side effects - like those done on various pharmaceuticals - would be tolerated without these kinds of controls. It goes back to the underlying scientific question of the chicken or the egg. It's possible that taking birth control affects one's mate preferences. It's also possible that those with certain mate preferences are more interested in taking birth control, particularly those interested in the pill over other contraceptive methods like condoms. The studies examined in this review lack the power and structure to determine the difference. After all, studies have shown that there are differences in contraceptive use between political, religious, and age groups. Is it not entirely likely that underlying factor might stimulate a woman to be attracted to 'boyish' men and take birth control, like her religious preferences? The only study covered in the review which did, at least, compare women before and after taking the pill, did not randomly select women for each group. The women elected to take the pill or not, which means it does not rule out all of these issues.Furthermore, among their logical conclusions, the authors suggest that taking the pill after starting a relationship may affect relationship satisfaction because a woman might change her mind about what she finds attractive. Call me a scientist, but can I have some data? This one ought to be easy to look at! Why speculate so broadly without any kind of data to back it up?The authors do note that their conclusions are 'speculative,' but it seems the mainstream media has overlooked this portion of the paper. The majority of their conclusions are evolutionary speculations, not scientifically supported theories. And there is danger in trying to see everything from an evolutionary perspective. Evolution is a complex combination of selection, random change, and genetic shifts. Don't panic, Jackie.Your rugged good looks won'tkeep women fro... Read more »
Alexandra Alvergne, & Virpi Lummaa. (2009) Does the contraceptive pill alter mate choice in humans?. Trends in Ecology and Evolution. info:/10.1016/j.tree.2009.08.003
- October 8, 2009
- 05:45 PM
- 920 views
The Protestant 'Work-Shy' Ethic?
At the start of the 20th Century, the sociologist Max Weber came up with a famous theory to explain why Northern Europe and North America were so prosperous: the Protestant Work Ethic.Basically, the idea was that a unique feature of Protestant Christianity is its emphasis on work as a duty to God. While other religions asked people to do things that were laborious and time consuming, only Protestantism (so the theory went) channelled that religious duty into productive work.It's important to take some time out here to understand what's meant by 'work ethic'. It certainly isn't simply productivity. The richest, most productive countries actually have the lowest work ethic.And a lack of 'work ethic' doesn't mean you're lazy or driven only by financial reward. In fact, educated people have a lower 'work ethic' than uneducated people. Clearly educated people aren't lazy - they work hard to get their qualifications and don't get paid to do it.So 'work ethic' is actually about working for no clear purpose - it's work for work's sake.Well, in the 100 years since there's been a lot of debate and no clear conclusion about whether Weber was right. But, in theory, it seems plausible. According to economists, people only do work if they are going to get some kind of reward. If you can convince them them that their reward will be 'magical' (some kind of spiritual reward in this life or the next) then you won't have to pay them as much.In modern economic terms, a Protestant would gain extra 'utility' from doing work, and so they would have additional motivation to work harder.But even if the idea did hold in the past, does it still work in the modern world? And if it does, how does it work in practice? A new paper by Hans Geser has taken a look.He scrutinized data from the Christians in the World Values Survey and found that, as far as work ethic goes, Protestantism probably isn't very much different from Catholicism and Orthodox Christianity.But he did find some interesting relationships with religion in general. Basically, people with stronger religious faith have a stronger work ethic. But other factors of religion - whether people took Church teaching seriously, whether they went to Church, or whether they prayed - seemed to have little or no effect.There was a surprise, however. Belief in an afterlife actually had a negative effect on work ethic.The effect of religion was small. Overall, only around 5% of the variation between people in work ethic is explained by religion. But Geser's analysis suggests that it's not due to religious teachings. And the promise of a reward in heaven actually has a negative effect.Which suggests that the reason religious people have a higher work ethic is that they expect to get a reward for it in this life, rather than the next.One last thing. The effect of religion, which is small even in poor countries, disappears in rich countries. That's not because the effects at an individual level get less. What happens is that the 'national average' intensity of religious faith has a cultural effect - increasing the work ethic of believers and non-believers.As countries get richer, their culture shifts from a religious to a secular one. And with that, the idea of working for the sake of work becomes marginalised. In rich countries, people work because they see a reason to do the work._______________________________________________________________________________________Hans Geser (2009). Work Values and Christian Religiosity: An Ambiguous Multidimensional Relationship Journal of Religion and Society, 11 (24)This work by Tom Rees is licensed under a Creative Commons Attribution-Share Alike 2.0 UK: England & Wales License.
... Read more »
Hans Geser. (2009) Work Values and Christian Religiosity: An Ambiguous Multidimensional Relationship. Journal of Religion and Society, 11(24). info:/
- October 8, 2009
- 05:00 PM
- 1,336 views
The virtual body illusion and immersive Second Life avatars
by Mo in Neurophilosophy
SECOND LIFE is an online "virtual world" which enables users to create a customised avatar, or digital persona, with which they interact with each other. Since its launch just over 6 years ago, it has become incredibly popular, with millions of "residents" now using it regularly to meet others, interact with them, and even to have sex. Users have also established virtual universities, businesses and a virtual economy.
Now, imagine a futuristic version of Second Life, in which avatars can transfer sensations to the bodies of their users. Such a scenario may seem far-fetched, but a team of European researchers has now taken us one step closer it. They demonstrate a perceptual illusion in which a computer-generated virtual body can be made to feel like one's real body, so that one can feel sensations from it and respond to it as if it were real.
Read the rest of this post... | Read the comments on this post...... Read more »
Slater, M. et al. (2009) Inducing illusory ownership of a virtual body . Front. Neurosci. info:/
- October 8, 2009
- 03:22 PM
- 1,553 views
Can Westerners understand emotions from a remote culture?
by Dave Munger in Cognitive Daily
Classical Indian dancing is a tradition that extends back 2,000 years. Unlike much Western dance, it is intended to express specific emotions and tell detailed stories. The Natyasastra, a text from the first or second century A.D., offers instructions for how to depict nine primary emotions, and these rules continue to be followed in Indian Classical dance today. This movie demonstrates one form of Indian Classical dance:
As you can see, each gesture has a highly-specific meaning, which, to my eyes, at least, isn't obvious. Yet much research has shown that many emotions share "universal" characteristics. Smiles and frowns seem to be recognized as positive and negative expressions nearly everywhere. So what about the traditional emotions of Indian dance? Can people who've never been exposed to the dances still understand the emotions the dancers intend to express?
In 2000, Ahalya Hejmadi, Richard Davidson, and Paul Rozin showed videos of a dancer (Hejmadi himself) depicting 10 emotions using Indian dance to 48 Americans and 47 Indians. (The emotions depicted were Anger, Disgust, Fear, Heroism, Humor, Love, Peace, Sadness, Lajya -- shame/embarrassment/shyness, and Wonder) Half the viewers were given a list of possible emotions and asked to pick which one was being depicted. The other half were asked to simply write a word or words to describe the emotion being depicted. A total of 30 videos were shown, three for each emotion.
Read the rest of this post... | Read the comments on this post...... Read more »
Hejmadi, A., Davidson, R., & Rozin, P. (2000) Exploring Hindu Indian Emotion Expressions: Evidence for Accurate Recognition by Americans and Indians. Psychological Science, 11(3), 183-187. DOI: 10.1111/1467-9280.00239
- October 8, 2009
- 03:18 PM
- 794 views
A Vaccine For White Line Fever?
by Neuroskeptic in Neuroskeptic
A study claims that it's possible to immunize against cocaine: Cocaine Vaccine for the Treatment of Cocaine Dependence in Methadone-Maintained Patients. But does it work? And will it be useful?The idea of an anti-drug vaccine is not new; as DrugMonkey explains in his post on this paper, monkeys were being given experimental anti-morphine vaccines as long ago as the 1970s. This one has been under development for years, but this is the first randomized controlled trial to investigate whether it helps addicts to use less of the drug.Martell et al, a Yale-based group, recruited 115 patients. They all used both cocaine and opiates, and were given methadone treatment to try to reduce their opiate use. The reason why the authors chose to focus on these patients is that the methadone keeps people coming back for more and makes them less likely to drop out of the study, or as they put it, "retention in methadone maintenance programs is substantially better than in primary cocaine treatment programs. We also offered subjects $15 per week to enhance retention."The vaccine consists of a bacterial protein (cholera toxin B-subunit) chemically linked to a cocaine-like molecule, succinylnorcocaine. Like all vaccines, it works by provoking an immune response. The bacterial protein triggers the production of antibodies, proteins which recognize and bind to specific targets.In this case, the antibodies bind cocaine (anti-cocaine IgG) because of the succinylnorcocaine in the vaccine. Once a molecule of cocaine is bound to the antibody, it's effectively out of commission, as it cannot enter the brain. So, the vaccine should reduce or abolish the effects of the drug. The control group were given a dummy placebo vaccine.The results? Biologically speaking, the vaccine worked, but in some people more than others. Out of the 55 subjects who were given the active vaccine, all but one produced anti-cocaine IgG. However, the amount of antibodies produced varied widely. Also, the response was short-lived. The vaccine was given 5 times over the first 12 weeks, but antibody levels did not peak until week 16, after which they fell rapidly.And the key question - did it reduce cocaine use? Well, sort of. The authors measured drug use in terms of the proportion of urine samples which were cocaine-free. In the active vaccine group, the proportion of drug-free urine samples was higher over weeks 9 to 16, when the antibody levels were high, and this was statistically significant (treatment x time interaction: Z=2.4, P=.01). As expected, the benefit was greater in the people who made lots of antibodies (43 μg/mL) (treatment x time interaction: Z=4.8, P less than .001). But the effect was pretty small:The bottom line was about 10% more urine samples testing negative, and even that was only true in the minority (38%) of people who responded well to the vaccine! Not very impressive, but on the other hand, the number of drug-free urine tests is a very crude measure of cocaine use. It doesn't tell us how much coke the patients used at a time, or how many times they used it per day.Also, bear in mind that if it works, this vaccine might increase cocaine use in some people, at least at first. By binding and inactivating some of the cocaine in the bloodstream, the vaccine would mean you'd need to take more of the drug in order to feel the effects. It's curious that the authors relied on just one crude outcome measure and didn't ask the patients to describe the effects in more detail.So, these are some interesting results, but the vaccine clearly needs a lot of work before it becomes clinically useful, as the authors admit - "Attaining high (43 μg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters." Quite an admission given that this study was partially funded by Celtic Pharmaceuticals, who make the vaccine.It's also questionable whether any vaccine will be truly beneficial in treating cocaine addiction. Such a vaccine would be a way of reducing the temptation to use cocaine. In this sense, it would be just like naltrexone for heroin addicts, which blocks the effects of the drug. Or disulifram (Antabuse) for alcoholics, which makes drinking alcohol cause horrible side effects. Essentially, these treatments are ways of artificially boosting your "self-control", and they work.But we've had naltrexone and disulifram for many years. They're cheap and safe. But we still have heroin addicts and alcoholics. This is not to say that they're never helpful - some people find them very useful. But they haven't eradicated addiction because addiction is not something that can be cured with a pill or an injection.Addiction is a pattern of behaviour, and medications might help people to break free of it, but the causes of addiction are social, economic and psychological as well as biological. People turn to drugs and alcohol when there's nowhere else to turn, and unfortunately, there's no vaccine against that.Martell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Gardner T, & Kosten TR (2009). Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Archives of general psychiatry, 66 (10), 1116-23 PMID: 19805702... Read more »
Martell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Gardner T, & Kosten TR. (2009) Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Archives of general psychiatry, 66(10), 1116-23. PMID: 19805702
- October 8, 2009
- 11:04 AM
- 1,389 views
Zinc and the common cold
by Vincent Racaniello in virology blog
Shortly after I developed sore throat, cough, and congestion last week, a package of 'Cold - Eeze' materialized on my kitchen counter. The writing on the package of zinc-laden lozenges promised to 'shorten your cold', and noted that they were 'clinically proven to reduce the duration of the common cold'. Do zinc lozenges have any effect on the common cold?... Read more »
Korant BD, Kauer JC, & Butterworth BE. (1974) Zinc ions inhibit replication of rhinoviruses. Nature, 248(449), 588-90. PMID: 4363085
Geist FC, Bateman JA, & Hayden FG. (1987) In vitro activity of zinc salts against human rhinoviruses. Antimicrobial agents and chemotherapy, 31(4), 622-4. PMID: 3038000
Krenn, B., Gaudernak, E., Holzer, B., Lanke, K., Van Kuppeveld, F., & Seipelt, J. (2008) Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections. Journal of Virology, 83(1), 58-64. DOI: 10.1128/JVI.01543-08
Roxas M, & Jurenka J. (2007) Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations. Alternative medicine review : a journal of clinical therapeutic, 12(1), 25-48. PMID: 17397266
- October 8, 2009
- 10:52 AM
- 762 views
Monogamous alligators in Louisiana
by Katie Kline in EcoTone
Photo by Phillip ‘Scooter’ Trosclair.
Birds are often touted as the monogamists of the animal kingdom, with most bird species mating with the same individual and displaying biparental care, sometimes for many years. Their cousins, the reptiles, are no match for their faithfulness: most reptiles show no mate fidelity, let alone parental care.
But a new [...]
... Read more »
LANCE, S., TUBERVILLE, T., DUECK, L., HOLZ-SCHIETINGER, C., TROSCLAIR, P., ELSEY, R., & GLENN, T. (2009) Multiyear multiple paternity and mate fidelity in the American alligator, . Molecular Ecology. DOI: 10.1111/j.1365-294X.2009.04373.x
- October 8, 2009
- 10:00 AM
- 562 views
Science News: Week of October 4, 2009
by Susan Steinhardt in BioData Blogs
Our weekly compilation of science news for the week of October 4, 2009.... Read more »
Brusatte, S., Carr, T., Erickson, G., Bever, G., & Norell, M. (2009) A long-snouted, multihorned tyrannosaurid from the Late Cretaceous of Mongolia. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0906911106
Parks, J., Guo, H., Momany, C., Liang, L., Miller, S., Summers, A., & Smith, J. (2009) Mechanism of Hg−C Protonolysis in the Organomercurial Lyase MerB. Journal of the American Chemical Society, 131(37), 13278-13285. DOI: 10.1021/ja9016123
- October 8, 2009
- 09:15 AM
- 2,023 views
New mega ring around Saturn discovered using Spitzer
by Dave Strickland in Exploding Galaxies and other Catastrophysics
Infrared observations using the Spitzer Space Telescope, published by Verbiscer et al (2009, Nature), have revealed the largest known ring around Saturn, an annulus of very tenuous material extending between 6 million and 18 million kilometers from Saturn, and tilted by 27 degree from the plane of the traditional rings (which only extend out to ~240,000 km).The material in the new ring comes from the battered and cratered moon Phoebe. Of more interest, this new dust ring explains why the leading side of Iapetus is so much darker than the rest of it - the dark front surface of Iapetus is material from the ring swept up by Iapetus as it orbits at the inner edge of the new ring.In truth a link between the dark front of Iapetus and Phoebe has been suspected before now, as the composition of the dark material is very similar to that of Phoebe based on near IR spectroscopy with Cassini. What the Spitzer observations reveal is the presence of the dust ring and hence the mechanism of material transfer from Phoebe to Iapetus.Although the ring is physically huge, with a volume of ~5e21 km^3 (this is my BOTE calculation. As far as I can tell Verbiscer et al do not quote a volume), it is incredibly tenuous, and if all the material within it were collected back into one place it would possibly only occupy ~ 1 km^3 of rock, i.e. the volume of a crater on Phoebe.The other interesting thing is that the material migrates inwards under the influence of radiation pressure. From Verbiscer et al:On long timescales, collisions and inward transport become important. Collision with Phoebe, the dominant loss mechanism for particles larger than several centimetres in size, takes on the order of 1010 years. Re-radiation of absorbed sunlight exerts an asymmetric force on dust grains, causing them to spiral in towards Saturn with a characteristic timescale of 1.5 105rg years where rg is the particle radius in micrometres. This force brings all centimetre-sized and smaller material to Iapetus and Titan unless mutual particle collisions occur first. The rate of mutual collisions depends on the size distribution of the ring particles and optical depth; if the ring were comprised entirely of 10 m grains, then the collisional timescale would be tens of millions of years, which is comparable to the inward drag timescale. Most material from 10 m to centimetres in size ultimately hits Iapetus, with smaller percentages striking Hyperion and Titan3.References:Verbiscer, A., Skrutskie, M., & Hamilton, D. (2009). Saturn's largest ring Nature DOI: 10.1038/nature08515BBC article published by Jonathan Amos. 2009/10/08 (the source of the nice graphic shown above).Spitzer press release, 2009/10/06.... Read more »
Verbiscer, A., Skrutskie, M., & Hamilton, D. (2009) Saturn's largest ring. Nature. DOI: 10.1038/nature08515
- October 8, 2009
- 07:00 AM
- 993 views
Coastal birds decline as development rises...
by Rob Goldstein in Conservation Maven
Researchers look at 29-years of data in Texas and find that coastal birds have declined as development has risen...read more... Read more »
Foster, C., Amos, A., & Fuiman, L. (2009) Trends in Abundance of Coastal Birds and Human Activity on a Texas Barrier Island Over Three Decades. Estuaries and Coasts. DOI: 10.1007/s12237-009-9224-2
- October 8, 2009
- 02:47 AM
- 2,433 views
E-Mail A Blessing Or A Burden?
by Dr Shock in Dr Shock MD PhD
From recent research based on secondary analysis of data obtained from telephone interviews from a sample of 1003 email users the answer is not conclusive.
e-mail supports work performance, but at the same time contributes to negative effects that in the long run may affect motivation and satisfaction
In this research in which they also looked at [...]
Related posts:E-Mail Behavior Explained Human activity is hard to predict. In researching human...Computer Games at Work are Good For You I’ve told you that so now and than I...Shrink Blogs When starting this blog I searched for other psychiatrists...
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Mano, R., & Mesch, G. (2009) E-mail characteristics, work performance and distress. Computers in Human Behavior. DOI: 10.1016/j.chb.2009.08.005
- October 8, 2009
- 12:29 AM
- 682 views
The genomic history of a breast cancer revealed
by Keith Robison in Omics! Omics!
Today's Nature contains a great paper which is one more step forward for cancer genomics. Using Illumina sequencing a group in British Columbia sequenced both the genome and transcriptome of a metastatic lobular (estrogen receptor positive) breast cancer. Furthermore, they searched a sample of the original tumor for mutations found in the genome+transcriptome screen in order to identify those that may have been present early vs. those which were acquired later.From the combined genome sequence and RNA-Seq data they found 1456 non-synonymous changes which was then trimmed to 1178 after removing pseudogenes and HLA sequences. 1120 of these could be re-assayed by Sanger sequencing of PCR amplicons from both normal DNA and the metastatic samples -- 437 of these were confirmed. Most of these (405) were found in the normal sample. Of the 32 remaining, 2 were found only in the RNA-Seq data, a point to be addressed later below. Strikingly, none of the mutated genes were found in the previous whole-exome sequencing (by PCR+Sanger) of breast cancer, though those samples were of a different subtype (estrogen receptor negative).There are a bunch of cool tidbits in the paper, which I'm sure I won't give full justice to here but I'll do my best. For example, several other papers using RNA-Seq on solid cancers have identified fusion proteins, but in this paper none of the fusion genes suggested by the original sequencing came through their validation process. Most of the coding regions with non-synonymous mutations have not been seen to be mutated before in breast cancer, though ERBB2 (HER2, the target of Herceptin) is in the list along with PALB2, a gene which when mutated predisposes individuals to several cancers (and is also associated with BRCA2). The algorithm (SNVMix) used for SNP identification & frequency estimation is a good example of an easter egg, a supplementary item that could easily be its own paper.One great little story is HAUS3. This was found to have a truncating stop codon mutation and the data suggests that the mutation is homozygous (but at normal copy number) in the tumor. A further screen of 192 additional breast cancers (112 lobular and 80 ductal) for several of the mutations found no copies of the same hits seen in this sample, but two more truncating mutations in HAUS3 were found (along with 3 more variations in ERBB2 within the kinase domain, a hotspot for cancer mutations). HAUS3 is particularly interesting because until about a year ago it was just C4orf15, an anonymous ORF on chromosome 15. Several papers have recently described a complex ("augmin") which plays a role in genome stability, and HAUS3 is a component of this complex. This starts smelling like a tumor suppressor (truncating mutations seen repeatedly; truncating mutation homozygous in tumor; protein in function often crippled in cancer), and I'll bet HAUS3 will be showing up in some functional studies in the not too distant future.Resequencing of the primary tumor was performed using amplicons targeting the mutations found in the metastatic tumor. These amplicons were small enough to be spanned directly by paired-end Illumina reads, obviating the need for library construction (a trick which has shown up in some other papers). By using Illumina sequencing for this step, the frequency of the mutation in the sample could be estimated. It is also worth noting that the primary tumor sample was a Formalin Fixed Paraffin Embedded slide, a way to preserve histology which is notoriously harsh on biomolecules and prone to sequencing artifacts. Appropriate precautions were made, such as sequencing two different PCR amplifications from two different DNA extractions. The sequencing of the primary tumor suggests that only 10 of the mutations were present there, with only 4 of these showing a frequency consistent with being present in the primary clone and the others probably being minor components. This is another important filter to suggest which genes are candidates for being involved in early tumorigenesis and which are more likely late players (or simply passengers).One more cool bit I parked above: the 2 variants seen only in the RNA-Seq library. This suggested RNA editing and also consistent with this an RNA editase (ADAR) was found to be highly represented in the RNA-Seq data. Two genes (COG3 and SRP9) showed high frequency editing. RNA editing is beginning to be recognized as a widespread phenomenon in mammals (e.g. the nice work by Jin Billy Li in the Church lab); the possibility that cancers can hijack this for nefarious purposes should be an interesting avenue to explore. COG3 is a Golgi protein & links of the Golgi to cancer are starting to be teased out. SRP9 is part of the signal recognition particle involved in protein translocation into the ER -- which of course feeds the Golgi. Quite possibly this is coincidental, but it certainly rates investigating.One final thought: the next year will probably be filled with a lot of similar papers. Cancer genomics is gearing up in a huge way, with Wash U alone planning 150 genomes well before a year from now. It seems unlikely that those 150 genomes will end up as 150 distinct papers and more so it will be a challenge to do the level of follow-up in this paper on such a grand scale. A real challenge to the experimental community -- and the funding establishment -- is converting the tantalizing observations which will come pouring out of these studies into validated biological findings. With a little luck, biotech & pharma companies (such as my employer) will be able to convert those findings into new clinical options for doctors and patients. Sohrab P. Shah, Ryan D. Morin, Jaswinder Khattra, Leah Prentice, Trevor Pugh, Angela Burleigh, Allen Delaney, Karen Gelmon, Ryan Guliany, Janine Senz, Christian Steidl, Robert A. Holt, Steven Jones, Mark Sun, Gillian Leung, Richard Moore, Tesa Severson, Greg A. Taylor, Andrew E. Teschendorff, Kane Tse, Gulisa Turashvili, Richard Varhol, René L. Warren, Peter Watson, Yongjun Zhao, Carlos Caldas, David Huntsman, Martin Hirst, Marco A. Marra, & Samuel Aparicio (2009). Mutational evolution in a lobular breast tumor profiled at single nucleotide resolution Nature, 461, 809-813 : 10.1038/nature08489... Read more »
Sohrab P. Shah, Ryan D. Morin, Jaswinder Khattra, Leah Prentice, Trevor Pugh, Angela Burleigh, Allen Delaney, Karen Gelmon, Ryan Guliany, Janine Senz.... (2009) Mutational evolution in a lobular breast tumor profiled at single nucleotide resolution. Nature, 809-813. info:/10.1038/nature08489
- October 8, 2009
- 12:12 AM
- 714 views
"Better to Have Loved And Lost...
by Daniel Hawes in Ingenious Monkey | 20-two-5
A recent study looks at how a general human tendency to differentiate between causes of regret pays out at Black Jack tables in Las Vegas. They find that even gamblers exhibit strong omission bias. ... Read more »
Carlin B. . (2009) Fear and loathing in Las Vegas: Evidence from blackjack tables. Judgment and Decision Making, 4(5), 385-396. info:/
- October 7, 2009
- 06:54 PM
- 1,603 views
Understanding Cancer Part 2 – Telomerase, the Road to Immortality, and the Nobel Prize
by colinhockings in Blue Genes
Most denizens of the interwebs (at least of this corner of the interwebs) will have heard the announcement that the 2009 Nobel Prize in Physiology or Medicine will be given to Elizabeth Blackburn, Carol Greider and Jack Szostak for their work on telomeres – the structures found at the ends of human chromosomes. You may [...]... Read more »
Shay, J., & Keith, W. (2008) Targeting telomerase for cancer therapeutics. British Journal of Cancer, 98(4), 677-683. DOI: 10.1038/sj.bjc.6604209
- October 7, 2009
- 06:12 PM
- 632 views
Sacre bleu! French diet doesn’t meet nutrient recommendations
by Helen Jaques in In Sickness and In Health
French food is famous around the world. From the haute cuisine espoused by cordon bleu and the Michelin Guide to weird and wonderful dishes like frogs legs, the French are passionate about cooking and what they eat.
However, a study published recently in the Journal of Nutrition has found that the diet consumed by the majority [...]... Read more »
Maillot, M., Vieux, F., Ferguson, E., Volatier, J., Amiot, M., & Darmon, N. (2009) To Meet Nutrient Recommendations, Most French Adults Need to Expand Their Habitual Food Repertoire. Journal of Nutrition, 139(9), 1721-1727. DOI: 10.3945/jn.109.107318
- October 7, 2009
- 04:19 PM
- 700 views
Spoor of South African Dinos Analyzed
by Greg Laden in Greg Laden's Blog
A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. Read the rest of this post... | Read the comments on this post...... Read more »
Wilson, J., Marsicano, C., & Smith, R. (2009) Dynamic Locomotor Capabilities Revealed by Early Dinosaur Trackmakers from Southern Africa. PLoS ONE, 4(10). DOI: 10.1371/journal.pone.0007331
- October 7, 2009
- 04:00 PM
- 779 views
Gen-F Scientists Ignoring Social Networking
by sciencebase in Sciencebase Science Blog
A quick analysis of online social networks, such as LinkedIn and Xing would suggest that a mere 1 in 7 research scientists use such tools as part of their work. This contrasts starkly with the business world where uptake is up to 88%. In other words almost 9 out of every ten employees in the [...]Gen-F Scientists Ignoring Social Networking is a post from: Sciencebase Science Blog
... Read more »
Lackes, R., Siepermann, M., & Frank, E. (2009) Social networks as an approach to the enhancement of collaboration among scientists. International Journal of Web Based Communities, 5(4), 577. DOI: 10.1504/IJWBC.2009.028091
- October 7, 2009
- 03:58 PM
- 996 views
What conclusions can we draw from Neanderthal DNA pt.2
by Wintz in A Replicated Typo
4. Nuclear DNA: Forays into 3 billion base pairs
4.1 Before Vi-80
The Vindija-80 (Vi-80) specimen is an important find for geneticists: it yielded a minimally contaminated sample and provided those first steps into Neanderthal genomics.
Previously, attempts at retrieving ancient nuclear DNA sequences proved to be a notoriously difficult process, plagued with problems of degradation, contamination and [...]... Read more »
Green, R., Krause, J., Ptak, S., Briggs, A., Ronan, M., Simons, J., Du, L., Egholm, M., Rothberg, J., Paunovic, M.... (2006) Analysis of one million base pairs of Neanderthal DNA. Nature, 444(7117), 330-336. DOI: 10.1038/nature05336
Briggs AW, Good JM, Green RE, Krause J, Maricic T, Stenzel U, Lalueza-Fox C, Rudan P, Brajkovic D, Kucan Z.... (2009) Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science (New York, N.Y.), 325(5938), 318-21. PMID: 19608918
Krause J, Lalueza-Fox C, Orlando L, Enard W, Green RE, Burbano HA, Hublin JJ, Hänni C, Fortea J, de la Rasilla M.... (2007) The derived FOXP2 variant of modern humans was shared with Neandertals. Current biology : CB, 17(21), 1908-12. PMID: 17949978
Lalueza-Fox C, Römpler H, Caramelli D, Stäubert C, Catalano G, Hughes D, Rohland N, Pilli E, Longo L, Condemi S.... (2007) A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals. Science (New York, N.Y.), 318(5855), 1453-5. PMID: 17962522
Coop, G., Bullaughey, K., Luca, F., & Przeworski, M. (2008) The Timing of Selection at the Human FOXP2 Gene. Molecular Biology and Evolution, 25(7), 1257-1259. DOI: 10.1093/molbev/msn091
- October 7, 2009
- 02:21 PM
- 811 views
Beauty is “more” in the eye of the beholder…..
by Wayne Hooke in The Psychology of Beauty
Joshua Foster (2008) conducted a study that expands on the research that explores the role of visual and olfactory cues in attractiveness ratings. Previous studies – which found that olfactory cues may be as influential or more influential in evaluating attractiveness – have relied on retrospective reports from participants. Foster’s design utilized real-time, in-the-moment attractiveness [...]... Read more »
Foster, J. (2008) Beauty Is Mostly in the Eye of the Beholder: Olfactory Versus Visual Cues of Attractiveness. The Journal of Social Psychology, 148(6), 765-774. DOI: 10.3200/SOCP.148.6.765-774
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