Manipulating egg quality and brood mates is a strategy that is not uncommon for birds. In fact, this is an important tactic in the survival of species when food is scarce and territories are poor. The idea is that deteriorating environmental conditions will drive parents to invest more resources in the sex that maximizes their [...]... Read more »
FERRER, M., NEWTON, I., & PANDOLFI, M. (2009) Small Populations and Offspring Sex-Ratio Deviations in Eagles. Conservation Biology, 23(4), 1017-1025. DOI: 10.1111/j.1523-1739.2009.01215.x
by iayork in Mystery Rays from Outer Space
Norovirus (from J Virol. 82:2079-2088 (2008))
Noroviruses cause an unpleasant, but rarely serious, diarrhea and vomiting-type disease — “cruise ship flu”1 is one term for it. As well as cruise ships, nursing homes and hospitals and other more or less closed systems also see outbreaks of norovirus disease fairly regularly, and as you’d expect the elderly [...]... Read more »
Siebenga, J., Vennema, H., Zheng, D., Vinjé, J., Lee, B., Pang, X., Ho, E., Lim, W., Choudekar, A., Broor, S.... (2009) Norovirus Illness Is a Global Problem: Emergence and Spread of Norovirus GII.4 Variants, 2001–2007. The Journal of Infectious Diseases, 200(5), 802-812. DOI: 10.1086/605127
Lopman, B., Armstrong, B., Atchison, C., & Gray, J. (2009) Host, Weather and Virological Factors Drive Norovirus Epidemiology: Time-Series Analysis of Laboratory Surveillance Data in England and Wales. PLoS ONE, 4(8). DOI: 10.1371/journal.pone.0006671
by jebyrnes in I'm a chordata, urochordata!
As an ecologist working in temperate climes, I’ve been following the ocean acidification field with some interest. It’s always been obvious to me how acidification has enormous ramifications for coral reefs and other tropical marine ecosystems. They exist in warm waters already, often close to their thermal maxima. Acidifying the water [...]... Read more »
Gooding, R., Harley, C., & Tang, E. (2009) Elevated water temperature and carbon dioxide concentration increase the growth of a keystone echinoderm. Proceedings of the National Academy of Sciences, 106(23), 9316-9321. DOI: 10.1073/pnas.0811143106
by Anthropology.net in Anthropology.net
I recently completed a medical parasitology course as part of my medical education. One of the diseases we discussed was leishmaniasis. Leishmaniasis is a zoonotic disease that is transferred to humans from reservoir hosts via the sand fly vector. The sand fly injects the promastigote form of the parasite, and the parasite invades white blood [...]... Read more »
Costa, M., Matheson, C., Iachetta, L., Llagostera, A., & Appenzeller, O. (2009) Ancient Leishmaniasis in a Highland Desert of Northern Chile. PLoS ONE, 4(9). DOI: 10.1371/journal.pone.0006983
by Alejandro Montenegro-Montero in MolBio Research Highlights
Another week has gone by and some very interesting molbio blog posts have been aggregated into Researchblogging.org. Every week [see my inaugural post on the matter], I'll select some blog posts I consider particularly interesting in the field of molecular biology [see here to get a sense of the criteria that will be used], briefly describe them and list them here for you to check out.This week,... Read more »
Suzuki, H., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009) Modulation of microRNA processing by p53. Nature, 460(7254), 529-533. DOI: 10.1038/nature08199
Xue, Y., Wang, Q., Long, Q., Ng, B., Swerdlow, H., Burton, J., Skuce, C., Taylor, R., Abdellah, Z., & Zhao, Y. (2009) Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree. Current Biology. DOI: 10.1016/j.cub.2009.07.032
Sun, N., Panetta, N., Gupta, D., Wilson, K., Lee, A., Jia, F., Hu, S., Cherry, A., Robbins, R., Longaker, M.... (2009) Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0908450106
by Vincent Racaniello in virology blog
Experiments have been done in ferrets to determine how the 2009 pandemic H1N1 strain interacts with seasonal H3N2 and H1N1 viruses.... Read more »
Perez, D., Sorrell, E., Angel, M., Ye, J., Hickman, D., Pena, L., Ramirez-Nieto, G,, Kimble, B., & Araya, Y. (2009) Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection. PLoS Currents. info:other/RRN1011.2
by Journal Watch Online in Journal Watch Online
Fish feed substitutes can keep aquaculture from depleting oceans
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Naylor, R., Hardy, R., Bureau, D., Chiu, A., Elliott, M., Farrell, A., Forster, I., Gatlin, D., Goldburg, R., Hua, K.... (2009) Feeding aquaculture in an era of finite resources. Proceedings of the National Academy of Sciences, 106(36), 15103-15110. DOI: 10.1073/pnas.0905235106
by Keith Robison in Omics! Omics!
Normally this time of year I would be watching the weather forecasts checking for the dreaded early frost which slays tomato plants, often followed by weeks of mild weather that could have permitted further growth. Alas, this year that will clearly not be the case. A wet growing season and commercial stock contaminated with spores has led to an epidemic of late blight, and my tomato plants (as shown, with the night photography accentuating the horror) are being slaughtered. This weekend I'll clear the whole mess out & for the next few years plant somewhere else. Late blight is particularly horrid as it attacks both foliage and fruits -- many tomato diseases simply kill the foliage. What looked like promising green tomatoes a week ago are now disgusting brown blobs. Late blight is caused by Phytophora infestans, a fungus-like organism. An even more devastating historical manifestation of this ogre was the Great Irish Potato Famine and remains a scourge of potato farmers. Given my current difficulties with it, I was quite excited to see the publication of the Phytophora infestans genome sequence (by Sanger) in Nature today.A sizable chunk of the paper is devoted to the general structure of the genome, which tops out at 240Mb. Two related plant pathogens, P.sojae (soybean root rot) and P.ramorum (sudden oak death) come in only at 95Mb and 65Mb respectively. What accounts for the increase? While the genome does not seem to be duplicated as a whole, a number of gene families implicated in plant pathogenesis have been found.Also in great numbers are transposons. About a third of the genome are Gypsy-type retrotransposons. Several other classes of transposons are present also. In the end, just over a quarter (26%) of the genome is non-repetitive. While these transposons do not themselves appear to contain phytopathological genes, their presence appears to be driving expansion of some key families of such genes. Comparison of genomic scaffolds with the other two sequenced Phytophora show striking overall conservation of conserved genes, but with local rearrangements and expansion of the zones between conserved genes (Figure 1 plus S18 and S19). Continuing evolutionary activity in this space is shown by the fact that some of these genes are apparently inactivated but have only small numbers of mutations, suggesting very recent conversion to pseudogenes. A transposon polymorphism was also found -- an insertion in one haplotype which is absent in another (figure S9)A curious additional effect shown off in two-D plots of 5' vs. 3' intergenic length (Figure 2. Overall this distribution is a huge blob, but for some of the pathogenesis gene classes are clustered in the quadrant where both intergenic regions are large -- conversely many of the core genes are clustered in the graph in the "both small" quadrant. Supplemental Figure S2 shows rather strikingly how splayed the distribution is for P.infestans -- other genomes show much tighter distributions but P.infestans seems to have quite a few intergenic regions at about every possible scale.The news item accompanying the paper puts some perspective on all this: P.infestans is armed with lots of anti-plant weapons which enable it to evolve evasions to plant resistance mechanisms. A quoted plant scientist offers a glum perspectiveAfter taking 15 years to incorporate this resistance in a cultivar, it would take Phytophthora infestans only a couple of years to defeat it.. Chemical control of P.infestans reportedly works only before the infection is apparent and probably involves stuff I'd rather not play with. A quick side trip to Wikipedia finds that the genus is a pack of blights. Indeed, Phytophora is coined from the Greek for "plant destruction". Other horticultural curses from this genus include alder root rot, rhododendron root rot, cinnamon root rot (not of cinnamon, but rather various woody plants) and fruit rots in a wide variety of useful & yummy fruits including strawberries, cucumbers and coconuts. What an ugly family tree!The Wikipedia entry also sheds light on why these awfuls are referred to as "fungus-like". While they have a life cycle and some morphology similarities to fungi, their cell walls are mostly cellulose and molecular phylogenetics place them closer to plants than to fungi.So, the P.infestans genome sequence sheds light how this pathogen can shift its attacks quickly. Unfortunately, as with human genomic medicine, it will take a long time to figure out how to outsmart these assaults, particularly in a manner practical and safe for commercial growers and home gardeners alike.BJ Haas et al (2009). Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans Nature : 10.1038/nature08358... Read more »
BJ Haas et al. (2009) Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans. Nature. info:/10.1038/nature08358
by Atila Iamarino in Influenza A (H1N1) Blog – English
I received a comment from Paulo Amaral with amazing questions, leading me to advance this post. As follows, you can find the questions and the answer explaining what is relevant:
Would the annual vaccination against flu be liable for the low number of reports in elders?
What is the efficacy of the vaccine produced by mettles of [...]... Read more »
Smith, G., Bahl, J., Vijaykrishna, D., Zhang, J., Poon, L., Chen, H., Webster, R., Peiris, J., & Guan, Y. (2009) From the Cover: Dating the emergence of pandemic influenza viruses. Proceedings of the National Academy of Sciences, 106(28), 11709-11712. DOI: 10.1073/pnas.0904991106
Morens, D., Taubenberger, J., & Fauci, A. (2009) The Persistent Legacy of the 1918 Influenza Virus. New England Journal of Medicine, 361(3), 225-229. DOI: 10.1056/NEJMp0904819
Palese, P., Tumpey, T., & Garcia-Sastre, A. (2006) What Can We Learn from Reconstructing the Extinct 1918 Pandemic Influenza Virus?. Immunity, 24(2), 121-124. DOI: 10.1016/j.immuni.2006.01.007
Yu, X., Tsibane, T., McGraw, P., House, F., Keefer, C., Hicar, M., Tumpey, T., Pappas, C., Perrone, L., Martinez, O.... (2008) Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature, 455(7212), 532-536. DOI: 10.1038/nature07231
Centers for Disease Control and Prevention (CDC). (2009) Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR. Morbidity and mortality weekly report, 58(19), 521-4. PMID: 19478718
by Christie Wilcox in Observations of a Nerd
Last night I had this wonderful dream. It was a normal day in just about every way except I had this amazing ability. When I jumped, I was able to leap great distances and almost fly. No wings were involved - it was almost like I was able to levitate, and slowly drift between places. It was a very calm, serene feeling.Perhaps that's how the mice in Dr. Liu's lab felt. Advances in Space Research has published online today an accepted manuscript where researchers levitated mice. And, according to their observations, the mice took to the free-floating existence quite readily. The team first used a magnetic field to suspend large water droplets about 2 inches in diameter. Feeling good about themselves, they decided to try the trick with a mouse of similar size and weight. The little guy, weighing only 10 grams, was placed in a cage-like apparatus that allowed the researchers to film the experiment as well as give the mouse food and water while allowing droppings to fall through the bottom. Then, of course, they turned on the magnet. A static magnetic field with a strength of about 17T and large field gradient of 1.17 T/cm lifted the hapless mouse off the floor.At first, the mouse wasn't so keen on floating. It tried desperately to grab a hold of anything, and kicked around, causing itself to spin faster and faster. To alleviate some of the stress, researchers sedated the mouse slightly the next time. But before long - about 3-4 hours - even non-sedated mice began acting normally, including eating and drinking in their suspended state. The team saw no observable negative effects of such a strong magnetic field on the animals, though further research will be necessary to determine if prolonged exposure causes health issues. Previous studies have found that a lower level of magnetic field (9.4T) didn't negatively impact mice, even when they were exposed to it for 10 weeks, but the stronger field used for levitation may have unforeseen, adverse effects after a long time. While the researchers hope to use this technology for better understanding space flight and bone loss in astronauts, I think there are many applications. Carnival rides, for example. Oh come on - like you've never wanted to levitate!Liu, Y., Zhu, D., Strayer, D., & Israelsson, U. (2009). Magnetic levitation of large water droplets and mice Advances in Space Research DOI: 10.1016/j.asr.2009.08.033
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Liu, Y., Zhu, D., Strayer, D., & Israelsson, U. (2009) Magnetic levitation of large water droplets and mice. Advances in Space Research. DOI: 10.1016/j.asr.2009.08.033
by Daemios in Rudimenthos
... Read more »
Nelson, B. (2009) Data sharing: Empty archives. Nature, 461(7261), 160-163. DOI: 10.1038/461160a
Toronto International Data Release Workshop Authors. (2009) Prepublication data sharing. Nature, 461(7261), 168-170. DOI: 10.1038/461168a
Schofield, P., Bubela, T., Weaver, T., Portilla, L., Brown, S., Hancock, J., Einhorn, D., Tocchini-Valentini, G., Hrabe de Angelis, M., & Rosenthal, N. (2009) Post-publication sharing of data and tools. Nature, 461(7261), 171-173. DOI: 10.1038/461171a
by Jeremy Yoder in Denim and Tweed
One of the key observations in support of evolutionary theory is that similar lifestyles can lead distantly-related living things to evolve strikingly similar traits. Compare an echidna and a hedgehog, distantly related mammals with very similar lifestyles. This kind of convergence can occur on much smaller scales of time and space, too, as a new paper just released online by Proceedings of the Royal Society shows. Its authors demonstrate that populations of spadefoot toads have independently evolved the same response to competition from another toad species [$-a].
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Spea multiplicata, the New Mexico spadefoot toad. Photo by J.N. Stuart.As tadpoles, spadefoot toads (Spea multiplicata) have two feeding strategies: they can be omnivores, feeding on organic debris in the water around them; or carnivores, feeding on aquatic crustaceans and sometimes other tadpoles. The two strategies are linked to a developmental switch -- tadpoles that start eating crustaceans develop larger heads, the better to eat their fellows, presumably. This switch is handy in minimizing competition for food with another, related toad species, S. bombifrons. In ponds where S. multiplicata and S. bombifrons occur together, S. multiplicata tadpoles are much more likely to become omnivores, and S. bombibfrons are more likely to become carnivores, than is the case for either species when they're the only ones in the pond.
This solution to competition might have evolved two ways: it may have turned up once, in a single population of S. multiplicata, which was then able to colonize other ponds containing the competitor; or it may have emerged independently in multiple populations experiencing similar natural selection from competition. The new study's authors show that the second scenario is more likely by comparing the genetic similarity of multiple S. multiplicata populations to the frequency of their competitors, and showing that competition strength, not genetic relatedness, is the better predictor of how likely S. multiplicata tadpoles are to become omnivores.
References
Pfennig, D., & Frankino, W. (1997). Kin-mediated morphogenesis in facultatively cannibalistic tadpoles Evolution, 51 (6) DOI: 10.2307/2411019
Rice, A., Leichty, A., & Pfennig, D. (2009). Parallel evolution and ecological selection: replicated character displacement in spadefoot toads Proc. R. Soc. B DOI: 10.1098/rspb.2009.1337
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Pfennig, D., & Frankino, W. (1997) Kin-mediated morphogenesis in facultatively cannibalistic tadpoles. Evolution, 51(6), 1993. DOI: 10.2307/2411019
Rice, A., Leichty, A., & Pfennig, D. (2009) Parallel evolution and ecological selection: replicated character displacement in spadefoot toads. Proc. R. Soc. B. DOI: 10.1098/rspb.2009.1337
by Devin Drown in Coevolvers
In 2004, Otto and Nuismer published a theoretical paper on the evolution of sex where they examined a range of stereotyped models (e.g. gene-for-gene) of species interactions (both antagonistic and beneficial) that are often used by theoreticians. Their results indicated that sex and recombination were generally selected against regardless of the model of interaction given the assumptions of the quasi linkage equilibrium (QLE, in this case, weak selection and strong recombination). In their numerical simulations that explored parameter space potentially outside the assumptions of the QLE, they found that some cases of the matching-genotypes model (or a strict matching alleles model) of interactions would favor sex and recombination.Kouyos et al (2007) looked at a wide range of matching alleles models (MAM) and found that when selection was strong, some models would favor sex and recombination. Salathé et al (2008b) also provide evidence of strong selection favoring recombination under the MAM. However, both did find that the closer these models were to a multiplicative form of the MAM, sex and recombination were selected against. These multiplicative matching alleles models (MMAM) were described by Otto and Nuismer (2004) as the negative control in their numerical simulations because they never favored recombination. Their QLE results also indicated that this model of interaction should not generate linkage disequilibrium and therefore neither favor nor select against recombination. Contrary to this, in a surprising result by Kouyos et al (2007), their simulations found that there was strong selection against recombination (rather than no selection at all) in the parameter space near a MMAM.It was this surprising result that was explained in the paper that we read this past week for Coevolvers (Kouyos et al 2009). Here the authors investigated why this parameter space shows strong selection again recombination. In a MMAM, there are no epistatic interactions between the loci involved in the fitness of the interaction between host and parasite. Despite this, previous observations (Kouyos et al 2007) and the current simulations have shown that strong linkage disequilibrium is built up and maintained. It turns out that here that an interaction governed by the MMAM can equilibrate to a region of high complementarity. The importance of this is that this equilibrium is such that any recombination among the loci will generate genotypes that have a lower fitness and recombination should be selected against.I think that this recent paper (Kouyos et al 2009) sheds more light on specific potential microevolutionary mechanisms that drive the maintenance of recombination. We still need empirical test of some more of these new predictions. The challenge for empiricists is to find the right kind of systems and a challenge for the theoreticians is to help design the right kinds of experiments.While I have just touched on a couple of recent results testing aspects of the Red Queen Hypothesis, Salathé et al (2008a) produced a wonderful review of many of many recent theoretical results on the evolution of sex and recombination driven by host-parasite interactions. In addition, this group has another paper on this topic out recently in the American Naturalist (Salathé et al 2009) that I'm looking forward to reading.ReferencesKouyos, R., M. Salathe, and S. Bonhoeffer. 2007. The Red Queen and the persistence of linkage-disequilibrium oscillations in finite and infinite populations. BMC Evolutionary Biology 7:211.Kouyos, R. D., M. Salathé, S. P. Otto, and S. Bonhoeffer. 2009. The role of epistasis on the evolution of recombination in host-parasite coevolution. Theoretical Population Biology 75:1-13.Otto, S. P., and S. L. Nuismer. 2004. Species interactions and the evolution of sex. Science 304:1018-1020.Salathé, M., R. D. Kouyos, and S. Bonhoeffer. 2008a. The state of affairs in the kingdom of the Red Queen. Trends in Ecology & Evolution 23:439-445.Salathé, M., R. D. Kouyos, and S. Bonhoeffer. 2009. On the Causes of Selection for Recombination Underlying the Red Queen Hypothesis. The American Naturalist 174:S31-S42.Salathé, M., R. D. Kouyos, R. R. Regoes, and S. Bonhoeffer. 2008b. Rapid parasite adaptation drives selection for high recombination rates. Evolution 62:295-300.KOUYOS, R., SALATHE, M., OTTO, S., & BONHOEFFER, S. (2009). The role of epistasis on the evolution of recombination in host–parasite coevolution Theoretical Population Biology, 75 (1), 1-13 DOI: 10.1016/j.tpb.2008.09.007... Read more »
KOUYOS, R., SALATHE, M., OTTO, S., & BONHOEFFER, S. (2009) The role of epistasis on the evolution of recombination in host–parasite coevolution. Theoretical Population Biology, 75(1), 1-13. DOI: 10.1016/j.tpb.2008.09.007
by Katie Kline in EcoTone
Convergent evolution of large functional traits is not uncommon in nature; consider that wings have evolved in several lineages of animals to broaden niches that animals can fill. But more specific convergence, especially in sexual and territorial signals, is rare at best and stirs controversy in the scientific world.
On the surface, it would seem that [...]
... Read more »
Tobias, J., & Seddon, N. (2009) SIGNAL DESIGN AND PERCEPTION IN ANTBIRDS: EVIDENCE FOR CONVERGENT EVOLUTION VIA SOCIAL SELECTION . Evolution. DOI: 10.1111/j.1558-5646.2009.00795.x
by Jacob Aron in Just A Theory
What happens to fat left over from a liposuction procedure? Brad Pitt might choose to turn it in to soap, but scientists at Stanford University have figured out a surprising alternative: stem cells. Induced pluripotent stem (iPS) cells are highly sought after because of their ability to transform in to many other types of cells [...]... Read more »
Sun, N., Panetta, N., Gupta, D., Wilson, K., Lee, A., Jia, F., Hu, S., Cherry, A., Robbins, R., Longaker, M.... (2009) Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0908450106
by Zen Faulkes in NeuroDojo
The best cartoon shows – like Rocky and Bullwinkle, ReBoot, or Avatar: The Last Airbender – work on two levels. There’s one layer of meaning that kids pick up on, and another layer that their parents watching beside them pick up on. The same signal has different meanings to different audiences. This new paper by Moosman and colleagues investigates how one signal might do double duty in the animal kingdom.Fireflies (which in this case are beetles rather than flies) light up to attract mates. But this is a conspicuous signals, and a conspicuous signal has its downsides: eavesdroppers can pick up on those signals, and even imitate them to lure in prey. Moosman and colleagues suspected this flashing light had yet a third effect: to be a warning sign.This particular firefly, Photinus pyralis,is thought to have chemical compounds that make it distasteful to come predators. Another firefly, Photuris, eats these smaller Photinus, and gain the same defensive chemical compounds from their prey.In that case, is it possible that predators might come to recognize their flash as a warning colouration, like the bright colours of poison dart frogs or some venomous snakes? This paper ran several tests of this hypothesis.First, the authors confirmed that the three species of insect-eating bats they were examining and fireflies overlapped in both space and time: fireflies were signaling at times and places where bats were flying.Second, they examined a lot of bat poo for traces of firefly remains, and found none. They found plenty of other insects, including others that were firefly sized, suggesting that bats avoided these particular insects.Third, they gave captive bats food pellets containing portions of fireflies. Bats rejected food significantly more often if it contained traces of fireflies.At this point, all this is pretty strong evidence that bats don’t like to eat these bugs. But is it because the bats recognize the flashing light signal? The authors tested this capturing several wild bats, and exposing them to artificial lures that flashed... or not. If the lights were a warning sign in the bat’s mind, you’d predict more attacks on the non-flashing lures than the flashing lures.The behavioural results don’t strongly support the idea. Of the three bats species, only one, Eptesicus fuscus (shown), preferentially attacked the non-flashing lures, and the only the larger, Photuris-sized lures. The authors do point out that E. fuscus is the species that overlaps with the fireflies the most, and thus may be the bat that has the most to gain by recognizing a flash as a danger sign.Another potentially problematic aspect of their experimental design was that they presented the bats not with a natural, intermittent rate set of flashes, but with a super-firefly, continuous set of flashes. This might be okay, because greater stimuli often generate greater responses, but it’s also possible that the unnatural stimulus is getting an unnatural response.Given that only one of the six combinations of three bat species and two sizes of lures showed evidence of flashes being warning signs, this sentence in the conclusion paints the situation with far too wide a brush:In conclusion, bioluminescence of adult fireflies should indeed be considered in the context of a warning signal against bats(.)Although it is often important to show that something can happen, that this happens in only one out of six cases tested raises real questions about whether this does happen with regularity. The authors risk overreaching just a little past the data they have.ReferenceMoosman, Jr, P., Cratsley, C., Lehto, S., & Thomas, H. (2009). Do courtship flashes of fireflies (Coleoptera: Lampyridae) serve as aposematic signals to insectivorous bats? Animal Behaviour DOI: 10.1016/j.anbehav.2009.07.028... Read more »
Moosman, Jr, P., Cratsley, C., Lehto, S., & Thomas, H. (2009) Do courtship flashes of fireflies (Coleoptera: Lampyridae) serve as aposematic signals to insectivorous bats?. Animal Behaviour. DOI: 10.1016/j.anbehav.2009.07.028
by Jeremy in Agricultural Biodiversity Weblog
We’re used to thinking — or at least assuming — in agrobiodiversity conservation that genetic distance is a monotonically increasing function of geographic distance. It is, after all, a reflection of the great Waldo Tobler’s First Law of Geography: “Everything is related to everything else, but near things are more related than distant things.” And [...]... Read more »
BERTHOULY, C., DO NGOC, D., THÉVENON, S., BOUCHEL, D., NHU VAN, T., DANES, C., GROSBOIS, V., HOANG THANH, H., VU CHI, C., & MAILLARD, J. (2009) How does farmer connectivity influence livestock genetic structure? A case-study in a Vietnamese goat population. Molecular Ecology. DOI: 10.1111/j.1365-294X.2009.04342.x
by Keith Robison in Omics! Omics!
A second paper which triggered my current physical map madness is a piece (open access!) arguing for the adaptation of HAPPY mapping to next-gen sequencing. This is intriguing in part because I see (and have) a need for cheap & facile access to the underlying technologies but also because I think there are some interesting computational problems (not touched on the paper, as I will elaborate below) and some additional uses to the general approach.HAPPy mapping is a method developed by Simon Dear for physical mapping. The basic notion is that large DNA fragments (the size range determining several important parameters of the map; the maximum range between two markers is about 10 times the minimum resolution) are randomly gathered in pools which each contain approximately one half a genome equivalent. Practical issues limit the maximum size fragments to about 1Mb; any larger and they can't be handled in vitro. By typing markers across these pools, a map can be generated. If two markers are on different chromosomes or are farther apart than the DNA fragment size, then there will be no correlation between them. On the other hand, two markers which are very close together on a chromosome will tend to show up together in a pool. Traditionally, HAPPy pools have been typed by PCR assays designed to known sequences. One beauty of HAPPy mapping is that it is nearly universal; if you can extract high molecular weight DNA from an organism then a HAPPy map should be possible.The next-gen version of this proposed by the authors would make HAPPy pools as before but then type them by sequence sampling the pools. Given that a HAPPy pool contains many orders of magnitude less DNA than current next-gen library protocols require, they propose using whole-genome amplification to boost the DNA. Then each pool would be converted to a bar-coded sequencing library. The final typing would be performed by incorporating these reads into a shotgun assembly and then scoring each contig as present or absent in a pool. Elegant!When would this mapping occur? One suggestion is to first generate a rough assembly using standard shotgun sequencing, as this improves the estimate of the genome size which in turn enables the HAPPy pools to be optimally constructed so that any given fragment will be in 50% of the pools. Alternatively, if a good estimate of the genome size is known the HAPPy pools could potentially be the source of all of the shotgun data (this is hinted at).One possible variation to this approach would be to replace bar-coded libraries and WGA with Helicos sequencing, which can theoretically work on very small amounts of DNA. Fragmenting such tiny amounts would be one challenge to be overcome, and of course the Helicos generates much shorter, lower-quality reads than the other platforms. But, since these reads are primarily for building a physical map (or, in sequence terms driving to larger supercontigs), that may not be fatal.If going with one of the other next-gen platforms (as noted in the previous post in this series, perhaps microarrays make sense as a readout), there is the question of input DNA. For example, mammalian genomes range in size from 1.73pg to 8.40pg. A lot of next-gen library protocols seem to call for more like 1-10ug of DNA, or about 6 logs more. The HAPPy paper's authors suggest whole-genome amplification, which is reasonable but could potentially introduce bias. In particular, it could be problematic to allow reads from amplified DNA to be the primary or even a major source of reads for the assembly. As I've noted before, other approaches such as molecular inversion probes might be useful for low amounts, but have not been demonstrated to my knowledge with picograms of input DNA. However, today I stumbled on two papers, one from the Max Planck Institute and one from Stanford, which use digital PCR to quantitate next-gen libraries and assert that this can assist in successfully preparing libraries from tiny amounts of DNA. It may also be possible to deal with this issue by attempting more than the required number of libraries, determining which built successfully by digital PCR and then pooling a sufficient number of successful libraries.The desirable number of HAPPY libraries and the desired sequencing depth for each library are two topics not covered well in the paper, which is unfortunate. The number of libraries presumably affects both resolution and confidence in the map. Pretty much the entire coverage of this is the tail of one paragraph In the Illumina/Solexa system, DNA can be randomly sheared and amplified with primers that contain a 3 bp barcode. Using current instruments, reagents, and protocols, one Solexa "lane" generates ~120 Mb in ~3 million reads of ~40 bp. When each Solexa lane is multiplexed with 12 barcodes, for example, it will provide on average, ~10 Mb of sequence in ~250,000 reads for each sample. At this level of multiplexing, one Solexa instrument "run" (7 lanes plus control) would allow tag sequencing of 84 HAPPY samples. This means, one can finish 192 HAPPY samples in a maximum of three runs. New-generation sequencing combined with the barcode technique will produce innumerous amounts of sequences for assembly. Changing the marker system from direct testing of sequence-tagged sites by PCR to sequencing-based sampling has an important implication as discussed in the last post. If your PCR is working well, then if a pool contains a target it will come up positive. But with the sequencing, there is a very real chance of not detecting a marker present in a pool. This probability will depend on the size of the target -- very large contigs will have very little chance of being missed, but as contigs go smaller their probability of being missed goes up. Furthermore, actual size won't be as important as the effective size: the amount of sequence which can be reliably aligned. In other words, two contigs might be the same length, but if one has a higher repeat count that contig will be more easily detectable. These parameters in turn can be estimated from the actual data. The actual size of the pool is a critical parameter as well. So, the sampling depth (for a given haploid genome size) will determineIn any case, the problem of false negatives must be addressed. One approach is to only map contigs which are unlikely to have ever been missed. However, that means losing the ability to map smaller contigs. Presumably there are clever computational approaches to either impute missing data or simply deal with it.It should also be noted that HAPPy maps, like many physical mapping techniques, are likely to yield long-range haplotype information. Hence, even after sequencing one individual the approach will retain utility. Indeed, this seems to be the tack that Complete Genomics is taking to obtain this information for human genomes, though they call it Long Fragment Reads. It is worth noting that the haplotyping application has one clear difference from straight HAPPy mapping. In HAPPy mapping, the optimal pool size is one in which any given genome fragment is expected to appear in half the pools, which means pools of about 0.7X genome. But for haplotyping (and for trying to count copy numbers and similar structural issues), it is desirable to have the pools much smaller, as this information can only be obtained if a given region of the genome is haploid in that pool. Ideally, this would mean each fragment in its own pool (library), but realistically this will mean as small a pool size as one can make and still cover the whole genome in the targeted number of pools. Genomes of higher ploidies, such as many crops which are tetraploid, hexaploid or even octaploid, would probably require more pools with lower genomic fractions in order to resolve haplotypes.In conclusion, HAPPy mapping comes close to my personal ideal of a purely in vitro mapping system which looks like a clever means of preparing next-gen libraries. The minimum and maximum distances resolvable are about 10-fold apart, so more than one set of HAPPy libraries is likely to be desirable for an organism. Typically this is two sizes, since the maximum fragment size is around 1Mb (and may be smaller from organisms with difficult to extract DNA). A key problem to resolve is that HAPPy pools contain single digit picograms of DNA. Amplification is a potential solution but may introduce bias; clever library preparation (or screening) may be another approach. An open p... Read more »
Jiang Z, Rokhsar DS, & Harland RM. (2009) Old can be new again: HAPPY whole genome sequencing, mapping and assembly. International journal of biological sciences, 5(4), 298-303. PMID: 19381348
by Neuroskeptic in Neuroskeptic
According to a new paper in the prestigous journal PNAS, High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China.The earthquake, you'll remember, happened on 12th May last year in central China. Over 60,000 people died. The authors of this paper took 44 earthquake survivors, and 32 control volunteers who had not experienced the disaster.The volunteers underwent a "resting state" fMRI scan; survivors were scanned between 13 and 25 days after the earthquake. Resting state fMRI is simply a scan conducted while lying in the scanner, not doing anything in particular. Previous work has shown that fMRI can be used to measure resting state neural activity in the form of low-frequency oscillations.The authors found differences in the resting state low-frequency activity (ALFF) between the trauma survivors and the controls. In survivors, resting state activity was increased in several areas:"The whole-brain analysis indicated that, vs. controls, survivors showed significantly increased ALFF in the left prefrontal cortex and the left precentral gyrus, extending medially to the left presupplementary motor area... [and] region of interest (ROI) analyses revealed significantly increased ALFF in bilateral insula and caudate and the left putamen in the survivor group..."They also reported correlations between resting activity in some of these areas and self-reported anxiety and depression symptoms in the survivors.Finally, survivors showed reduced functional connectivity between a wide range of areas ("a distributed network that included the bilateral amygdala, hippocampus, caudate, putamen, insula, anterior cingulate cortex, and cerebellum.") Functional connectivity analysis measures the correlation in activity across different areas of the brain - whether the areas tend to activate at the same time or not.Now - what does all this mean? And does it help us understand the brain?The fact that there are differences between the two groups is not very informative or surprising. "Resting state" neural activity presumably reflects whatever is going through a person's mind. Recent earthquake survivors are going to be thinking about rather different things compared to luckier people who didn't experience such trauma. It doesn't take a brain scan to tell you that, but that's all these scans really tell us.But these weren't just any differences - they were particular differences in particular brain regions. Does that make knowing about them more interesting and useful?Not as such, because we don't know what they represent, or what causes them. So living through an earthquake gives you "Increased ALFF in the left prefrontal cortex" - but what does that mean? It could mean almost anything. The left prefrontal cortex is a big chunk of the brain, and its functions probably include most complex cognitive processes. Ditto for the other areas mentioned.The authors link their findings to previous work with frankly vague statements such as "The increased regional activity and reduced functional connectivity in frontolimbic and striatal regions occurred in areas known to be important for emotion processing". But anatomically speaking, most of the brain is either "fronto-limbic" or "striatal", and almost everywhere is involved in "emotion processing" in one way or another.So I don't think we understand the brain much better for reading this paper. Further work, building on these results, might give insights. We might, say, learn that decreased connectivity between Regions X and Y is because trauma decreases serotonin levels, which prevents signals being communicated between these areas, which is why trauma victims can't use X to deliberately stop recalling traumatic memories, which is what Y does.I just made that up. But that's a theory which could be tested. Much of today's neuroimaging research doesn't involve testable theories - it is merely the exploratory search for neural differences between two groups. Neuroimaging technology is powerful, and more advanced techniques are always being developed. What with resting state, functional connectivity, pattern-classification analysis, and other fancy methods, the scope for finding differences between groups is enormous and growing. So I'm being rather unfair in criticizing this paper; there are hundreds like it. I picked this one because it was published last week in a good journal.Exploratory work can be useful as a starting point, but at least in my opinion, there is too much of it. If you want to understand the brain, as opposed to simply getting published papers to your name, you need a theory sooner or later. That's what science is about.Lui, S., Huang, X., Chen, L., Tang, H., Zhang, T., Li, X., Li, D., Kuang, W., Chan, R., Mechelli, A., Sweeney, J., & Gong, Q. (2009). High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0812751106... Read more »
Lui, S., Huang, X., Chen, L., Tang, H., Zhang, T., Li, X., Li, D., Kuang, W., Chan, R., Mechelli, A.... (2009) High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0812751106
by Kristopher Hite in Tom Paine's Ghost
Two biochemically inspired limericks by Kristopher Hite1.)The proteosome proceeds to foragetransforming proteins to porridge if ubiquitin tagged Then subsequently baggedcatabolized and placed into storage2.)Hec1 and Nuf2 unitetogether coiled-up tight microtubule bound never coming unwoundto align all the chromosomes rightinspired by the following research...Yao, T. (2000). Cyclization of Polyubiquitin by the E2-25K Ubiquitin Conjugating Enzyme Journal of Biological Chemistry, 275 (47), 36862-36868 DOI: 10.1074/jbc.M006050200GUIMARAES, G., DONG, Y., MCEWEN, B., & DELUCA, J. (2008). Kinetochore-Microtubule Attachment Relies on the Disordered N-Terminal Tail Domain of Hec1 Current Biology, 18 (22), 1778-1784 DOI: 10.1016/j.cub.2008.08.012... Read more »
Yao, T. (2000) Cyclization of Polyubiquitin by the E2-25K Ubiquitin Conjugating Enzyme. Journal of Biological Chemistry, 275(47), 36862-36868. DOI: 10.1074/jbc.M006050200
GUIMARAES, G., DONG, Y., MCEWEN, B., & DELUCA, J. (2008) Kinetochore-Microtubule Attachment Relies on the Disordered N-Terminal Tail Domain of Hec1. Current Biology, 18(22), 1778-1784. DOI: 10.1016/j.cub.2008.08.012
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