The hypothesis that there exists world of life that is hitherto unknown has always seduced us. The Kraken, Mermaids, Loch-Ness monster, Bigfoot, Yeti. We are in love with the concept of life’s rarities. Very rarely, a new mammal, reptile, bird or fish is reported. That usually goes unnoticed by the mass media, unless they are unusual, (as in butt-ugly). As a rule, we are not excited by the discovery of yet another species of fish (although we should!) but more by the “freak-appeal” of that fish. It excites us that it is strange, unusual, completely different than anything we know. It makes us happy to know that sometimes life cannot be pigeonholed.... Read more »
Quince, C., Lanzén, A., Curtis, T., Davenport, R., Hall, N., Head, I., Read, L., & Sloan, W. (2009) Accurate determination of microbial diversity from 454 pyrosequencing data. Nature Methods, 6(9), 639-641. DOI: 10.1038/nmeth.1361
Sogin, M., Morrison, H., Huber, J., Welch, D., Huse, S., Neal, P., Arrieta, J., & Herndl, G. (2006) Microbial diversity in the deep sea and the underexplored "rare biosphere". Proceedings of the National Academy of Sciences, 103(32), 12115-12120. DOI: 10.1073/pnas.0605127103
Proteins in complex metazoans (like us) lost a whole lot of tyrosine along the way, according to a recent Science paper. Why do we and our fellow animals have less of this amino acid than our unicellular nephews?
If you would be a single-celled organism, you would be absolutely free to divide and multiply according to [...]... Read more »
Tan CS, Pasculescu A, Lim WA, Pawson T, Bader GD, & Linding R. (2009) Positive selection of tyrosine loss in metazoan evolution. Science (New York, N.Y.), 325(5948), 1686-8. PMID: 19589966
October is Breast Cancer Awareness Month, and the timing couldn’t be better. Our friends at the BC Cancer Agency published the whole genome sequencing of a breast cancer this week in a letter to Nature.
Using Illumina paired-end sequencing, Shah et al generated 141 Gbp of sequence to achieve 43x haploid coverage of a metastatic lobular [...]... Read more »
Shah, S., Morin, R., Khattra, J., Prentice, L., Pugh, T., Burleigh, A., Delaney, A., Gelmon, K., Guliany, R., Senz, J.... (2009) Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature, 461(7265), 809-813. DOI: 10.1038/nature08489
Ah, it doesn’t go away, does it? Or at least, we won’t let it.
That concept of ‘how many is enough?’ in conservation biology, the so-called ‘minimum viable population size‘, is enough to drive some conservation practitioners batty.
How many times have we heard the (para-) phrase: “It’s simply impractical to bring populations of critically endangered species [...]... Read more »
Traill, L.W., Brook, B.W., Frankham, R.R., & Bradshaw, C.J.A. (2009) Pragmatic population viability targets in a rapidly changing world. Biological Conservation. DOI: 10.1016/j.biocon.2009.09.001
Today's Friday Weird Science is going up late, because of extenuating circumstances. Sci-cat, Sci's constant blogging companion (someone has to keep those papers and books warm and furry!), managed to hop up on something Sci thought she could not reach, and stand curiously over a burning candle, wondering where that smell of burning fur was coming from. All would be lost had not I noticed the smell, spied the cat, and immediately dumped her in the sink where I happened to be doing dishes. Sci-cat STILL does not realize what danger she was in, and is now angry at Sci for yelling and soaking her with water. Small minds...
Sci is not burning candles anymore, despite the fact that they were pumpkin scented and awesome. Sci-home now smells like burned fur. And Sci then needed some drinks, and Sci-cat needed some treats, to calm them both down following the potential loss of Sci's furry blogging companion and paperweight.
On the other hand, I think I just found a GREAT excuse not to go on a date: "I'm sorry, I just CAN'T tonight, my cat is on fire..."
Today's weird science is HISTORICAL weird science, and is an AWESOME paper sent to me by the charming and handsome gg of SkullsintheStars. At first he wondered if we were close enough for him to send me a paper about bee sex. We ARE that close, gg, of course we are! :)
And yes, it's about bee sex. OLD FASHIONED bee sex. It's a paper from 1777, and so old that half the 's's are 'f's. This makes the paper even more amusing, because now, rather than reading "Discoveries on the Sex of Bees", I got to read "Difcoverief of the Sex of Bees". Whenever Sci reads one of these old papers, I want to pronounce the extra "f"s like "th"s and so I read the whole thing in my mind with a lisp.
Debraw, J. "Difcoveries on the Sex of Bees, explaining the manner in which their species is propagated; with an account of the utility that may be derived from thofe Difcoveries by the actual application of them to practice". Philosophical Transactions of the Royal Society of London, 1777.
Tempting as it if, Sci will not write the rest of the post like thif. Though it would give her many laughf.
And there's one other thing about this paper. It's completely and utterly wrong. But other than that, it's really awesome, and a testimony to this guy's sheer perseverance.
Read the rest of this post... | Read the comments on this post...... Read more »
Debraw, J., & Maskelyne, N. (1777) Discoveries on the Sex of Bees, Explaining the Manner in Which Their Species is Propagated; With an Account of the Utility That May Be Derived from Those Discoveries by the Actual Application of Them to Practice. By Mr. John Debraw, Apothecary to Addenbro. Philosophical Transactions of the Royal Society of London (1776-1886), 67(1), 15-32. DOI: 10.1098/rstl.1777.0004
Hilbert curve or Hilbert space-filling curve is a continuous fractal space-filling curve that densely fills higher-dimensional space without crossing itself. It was first described by the German mathematician David Hilbert in 1891. In a recent article Aiden et al. describe a new method called as Hi-C for reconstructing the three-dimensional architecture of the human genome which not only reveals folding principles of the human genome but also resembles a polymer analog of Hilbert's curve at the megabase scale. Their finding suggest that Chromosomes are organized in a fractal knot-free conformation or fractal globule that is densely packed while easily folded and unfolded contrary to what was previously hypothesized as an equilibrium globule. This study has shown that each Chromosome is organized into two separate compartments, keeping active genes accessible while sequestering unused DNA in a denser storage compartment. Each chromosome alternates between regions of active, gene-rich DNA and inactive, gene-poor stretches.Abstract We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes. Reference:Lieberman-Aiden, E., van Berkum, N., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B., Sabo, P., Dorschner, M., Sandstrom, R., Bernstein, B., Bender, M., Groudine, M., Gnirke, A., Stamatoyannopoulos, J., Mirny, L., Lander, E., & Dekker, J. (2009). Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome Science, 326 (5950), 289-293 DOI: 10.1126/science.1181369
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Lieberman-Aiden, E., van Berkum, N., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B., Sabo, P., Dorschner, M.... (2009) Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome. Science, 326(5950), 289-293. DOI: 10.1126/science.1181369
... Read more »
Cooley, H., Wielgus, R., Koehler, G., Robinson, H., & Maletzke, B. (2009) Does hunting regulate cougar populations? A test of the compensatory mortality hypothesis. Ecology, 90(10), 2913-2921. DOI: 10.1890/08-1805.1
Most of data sharing policies share some common principles such as protecting the cumulative data outputs, recognizing data as a public good and data sharing as strong value chains of innovation for subsequent scientific exploitation. A improved data access and sharing not only helps to maximize the research potential but it also reinforces open scientific research which encourages diversity of analysis and opinion. In a latest article published in October 9 issue of journal Science, Dawn Field, John Wilbanks and others highlights several issues related to convergence and confluence of data sharing efforts-1. Data managing versus data sharing Funding agencies are more focused on data managing efforts such creating institutional infrastructure and repositories rather than data sharing. Authors suggest that although such centralization efforts provides economy of scale, institutional memory, and reusable capability, in long term it also finds a substantial direct cost that may compete with research funding.2. Heterogeneity and seamless interoperabilityDespite the fact that most funding agencies are committed to data sharing efforts they can hardly avoid the heterogeneity and overlap of these kind of efforts due to different types of communities served by each funder and the data types they generate. Seamless interoperability should be prime focus in this kind of matters.Image credits Biosharing3. Challenges due to proliferation of standardization effortsThere is an exponential increase in number of community-driven efforts to create minimal information guidelines, ontologies and file-format projects. On one side it seems a positive sign of community engagement, but on the other side this proliferation brings new challenges because most of these projects are focused on a particular biological domain and due to their domain specific virtue most of these projects are fragmented and not suitable for the interoperability. Also on several occasions one can observe unnecessary overlaps and duplication of these efforts.4. Intellectual and ethical issuesNot all but few researchers' are concerned about intellectual ownership and the commercial aspects of their research work. Ethical issues such as whether or not patient specific data should be open especially to avoid the potential misuses (For instance a recent UK government scheme to establish nationality through DNA testing using recent development of large SNP databases has sparked a intense debate)5. Lack of fundingLast but not least lack of funding may be detrimental for these substantial and long term undertakings.RecommendationsFurther authors recommend that there should be a single detailed multi-level data sharing guideline which can serve as a template for policy documents at the various levels such as funder, community, and project level. For enforcement of policy they suggest that funding agency should bring a clear mandate for the inclusion of data-sharing plans in grant applications including the compulsory deposition of data generated due to funding of research in appropriate databases within a specified time line adhering with best standards.They also emphasize the requirement of a centralize hub which can build essential linkages between various topdown(guided by public and private funding agencies) and buttom-up (grassroots developments such as Science Commons, MIBBI, OBO, BioPortal, FUGE etc) data sharing initiatives to serve a "one-stop shop" for those who are in pursuit of data sharing policies and information. Reference:Field, D., Sansone, S., Collis, A., Booth, T., Dukes, P., Gregurick, S., Kennedy, K., Kolar, P., Kolker, E., Maxon, M., Millard, S., Mugabushaka, A., Perrin, N., Remacle, J., Remington, K., Rocca-Serra, P., Taylor, C., Thorley, M., Tiwari, B., & Wilbanks, J. (2009). 'Omics Data Sharing Science, 326 (5950), 234-236 DOI: 10.1126/science.1180598
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I would never select Treponema pallidum as my experimental model if I had to study gene regulation in a spirochete. The main problem is that no one has figured out how to grow T. pallidum in any type of culture medium. T. pallidum can be propagated only by growing the spirochete in the testes of rabbits. Consequently, investigators have not even begun to develop the genetic tools (e.g., gene knock outs, shuttle plasmids) necessary to unravel the regulatory mechanisms that control T. pallidum gene expression.Despite the limitations imposed by T. pallidum upon those who wish to study gene regulation, a group of syphilis researchers at the University of Washington in Seattle have started to dissect the regulation of several members of the 12-gene tpr (Treponema pallidum repeat) family. No one has figured out what the Tpr proteins do, but syphilis researchers are interested in them in part because they show how the immune response battles T. pallidum infections. For example, antibodies generated against TprK during infection bind to TprK exposed on the surface of T. pallidum and mark them for destruction by macrophages. More recent studies suggest that TprK undergoes antigenic variation (a topic of a future post), which may allow T. pallidum to persist in the host.The Seattle group's studies on gene regulation have focused on the Subfamily II tpr genes tprE, tprG, and tprJ, as reported in the journal Molecular Microbiology. The sequences upstream of their transcription start sites contain a sequence that closely matches the consensus binding sequence for the E. coli global transcriptional regulator CRP (cAMP regulatory protein), also known as CAP (catabolite activator protein). The T. pallidum genome encodes a CRP homolog designated TP0262. In E. coli and a few other Gram negatives, CRP is an integral component of the complex network of transporter, regulatory, and enzymatic proteins that allow bacteria to selectively metabolize the preferred sugar, usually glucose, from those available in the environment. When glucose is absent, the enzyme adenylate cyclase is activated and synthesizes the second messenger cAMP (cyclic AMP), which turns on CRP by allosteric activation. (Here's a nice description of the allosteric activation of CRP.) The cAMP-CRP complex then binds upstream of various promoters and activates transcription by recruiting RNA polymerase to the promoter. Additional layers of regulation ensure that the genes are transcribed only when the sugar that is to be broken down by the gene products is present.Because it's not possible to examine gene regulation in T. pallidum, the Seattle group transferred the tpr genes to E. coli, a genetically pliable bacterium. They fused each tpr gene, including the upstream sequences containing the proposed CRP binding site and the promoter, to a gene whose product is easily measurable, green fluorescent protein (gfp). They then introduced the plasmid carrying the gene fusion into an E. coli strain missing its crp gene so that they could measure tpr-driven GFP levels in the presence and absence of a second plasmid expressing TP0262. They found that TP0262 increased tprE'-gfp and tprJ'-gfp fusion expression while decreasing trpG'-gfp expression. The ability of TP0262 to control tpr'-gfp expression was lost when the CRP binding site was removed from the fusion constructions. They also showed that control of the tprJ'-gfp fusion by TP0262 was lost when the adenylate cyclase gene in E. coli was removed, indicating that cAMP was needed to activate TP0262 (data for tprE and tprG were not presented). Their in vitro experiments demonstrated binding of purified recombinant TP0262 to the proposed CRP binding site upstream of the three tpr genes by DNase I protection and gel shift assays.What was missing from the study, as acknowledged by the authors, were experiments to demonstrate that TP0262 does the same thing in T. pallidum. For future studies, they plan to show that TP0262 is bound upstream of the Subfamily II tpr genes in T. pallidum by chromatin immunoprecipitation, which entails determining the sequence of the segment of DNA that is bound when TP0262 is immunoprecipitated from a T. pallidum extract. Such experiments would not require genetic manipulation or the ability to cultivate T. pallidum. It would only require harvesting a large number of T. pallidum spirochetes from infected rabbits.What signal does TP0262 respond to? Does it respond to the glucose found in the host? The insightful Commentary by Radolf and Desrosiers sheds some light on the question. They note that T. pallidum is missing the special transporter genes that in E. coli encode the components necessary to link sugar availability to cAMP and CRP. They surmise that TP0262 has thus been freed to regulate genes not related to sugar metabolism, such as the tpr genes. Since CRP is a global transcriptional regulator in other bacteria, it is likely to regulate expression of not only the Subfamily II tpr genes but also additional genes in T. pallidum.Near the end of their commentary, Radolf and Desrosiers made one comment that stood out:One of the most important outcomes of the present study is that it will help put to rest the pregenomic view of the syphilis spirochaete as a transcriptionally invariant organism.Maybe I'm too young to appreciate their point, but I can't believe that there ever was a time when syphilis researchers believed that T. pallidum genes were not regulated!Featured articlesGiacani, L., Godornes, C., Puray-Chavez, M., Guerra-Giraldez, C., Tompa, M., Lukehart, S.A., & Centurion-Lara, A. (2009). TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. pallidum Molecular Microbiology, 72 (5), 1087-1099 DOI: 10.1111/j.1365-2958.2009.06712.x... Read more »
Giacani, L., Godornes, C., Puray-Chavez, M., Guerra-Giraldez, C., Tompa, M., Lukehart, S.A., & Centurion-Lara, A. (2009) TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. pallidum . Molecular Microbiology, 72(5), 1087-1099. DOI: 10.1111/j.1365-2958.2009.06712.x
Radolf, J.D., & Desrosiers, D.C. (2009) Treponema pallidum, the stealth pathogen, changes, but how? . Molecular Microbiology, 72(5), 1081-1086. DOI: 10.1111/j.1365-2958.2009.06711.x
The new Science has an extremely impressive paper tackling the problem of orphan enzymes. Due primarily to Watson-Crick basepairing, our ability to sequence nucleic acids has shot far past our ability to characterize the proteins they may encode. If I want to measure an RNA's expression, I can generate an assay almost overnight by designing specific real-time PCR (aka RT-PCR aka TaqMan) probes. If I want to analyze any specific protein's expression, it generally involves a lot of teeth gnashing & frustration. If you're lucky, there is a good antibody for it -- but most times there is either no antibody or one of unknown (and probably poor) character. Mass spec based methods continue to improve, but still don't have an "analyze any protein in any biological sample anytime" character (yet?).One result of this is that there are a lot of ORFs of unknown function in any sequenced genome. Bioinformatic approaches can make guesses for many of these and those guesses are often around enzymatic activity, but a bioinformatic prediction is not proof and the predictions are often quite vague (such as "hydrolase"). Structural genomics efforts sometimes pull in additional proteins whose sequence didn't resemble anything of known function, but whose structure has enzymatic characteristics such as nucleotide binding pockets. There have been one or two of such structures de-orphaned by virtual screening, but these are a rarity.Attempts have been made at high-throughput screening of enzyme activities. For example, several efforts have been published in which cloned libraries of proteins from a proteome were screened for enzyme activity. While these produced initial papers, they've never seemed to really catch fire.The new paper is audacious in providing an approach to detecting enzyme activities and subsequently identifying the responsible proteins, all from protein extracts. The key trick is an array of golden nano anglerfish -- well, that's how I imagine it. Like an anglerfish, the gold nanoparticles dangle their chemical baits off long spacers (poly-A, of all things!). In reverse of an anglerfish, the bait complex glows after it has been taken by its prey, with a clever unquenching mechanism activating the fluorophore and marking that a reaction took place. But the real kicker is that like an anglerfish, the nanoparticles seize their prey! Some clever chemistry around a bound Cobalt ion (which I won't claim to understand)results in linking the enzyme to the nanoparticle, from which it can be cleaved, trypsinized and identified by mass spectrometry. 1676 known metabolites and 807 other compounds of interest were immobilized in this fashion. As one test, the researchers applied separately extracts of the bacteria Pseudomonas putida and Streptomyces coelicolor to arrays. Results were in quite strong agreement with the existing bioinformatic annotations of these organisms, in that the P.putida extract's pattern of metabolized and not metabolized substrates strongly coincided with what the informatics would predict and the same was true for S.coelicolor (with a PFurther work was done with environmental samples. However, given the low protein abundance from such samples, these were converted into libraries cloned into E.coli and then the extracts from these E.coli strains analyzed. Untransformed E.coli was used to estimate the backgrounds to subtract -- I must confess a certain disappointment that the paper doesn't report any novel activities for E.coli, though it isn't clear that they checked for them (but how could you not!). The samples came from three extreme environments -- one from a hot, heavy metal rich acidic pool, one from oil-contaminated seawater and a third from a deep sea hypersaline anoxic region. From each sample a plethora of enzyme activities were discovered.Of course, there are limits to this approach. The tethering mechanism may interfere with some enzymes acting on their substrates. It may, therefore, be desirable to place some compounds multiple times on the array but with the linker attached at different points. It is unlikely we know all possible metabolites (particularly for strange bugs from strange places), so some enzymes can't be deorphaned this way. And sensitivity issues may challenge finding some enzyme activities if very few copies of the enzyme are present.On the other hand, as long as these issues are kept in mind this is an unprecedented & amazing haul of enzyme annotations. Application of this method to industrially important fungi & yeasts is another important area, and certainly only the bare surface of the bacterial world was scratched in this paper. Arrays with additional unnatural -- but industrially interesting -- substrates are hinted at in the paper. Finally, given the reawakened interest in small molecule metabolism in higher organisms & their diseases (such as cancer), application of this method to human samples can't be far behind. Ana Beloqui, María-Eugenia Guazzaroni, Florencio Pazos, José M. Vieites, Marta Godoy, Olga V. Golyshina,, Tatyana N. Chernikova, Agnes Waliczek, Rafael Silva-Rocha, Yamal Al-ramahi, Violetta La Cono, Carmen Mendez, José A. Salas, Roberto Solano, Michail M. Yakimov, Kenneth N. Timmis, Peter N. Golyshin, & Manuel Ferrer (2009). Reactome array: Forging a link between metabolome and genome Science, 326 (5950), 252-257 : 10.1126/science.1174094... Read more »
Ana Beloqui, María-Eugenia Guazzaroni, Florencio Pazos, José M. Vieites, Marta Godoy, Olga V. Golyshina,, Tatyana N. Chernikova, Agnes Waliczek, Rafael Silva-Rocha, Yamal Al-ramahi.... (2009) Reactome array: Forging a link between metabolome and genome. Science, 326(5950), 252-257. info:/10.1126/science.1174094
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
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
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
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 »
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
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 [...]
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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
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
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
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
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 »
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
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