Summary of foldit results in the 2008 Protein Structure Prediction competition (CASP8): "foldit players are on par, but not better than protein folding experts at trying to solve the same problem with all tools available to them. It also appears that foldit outperformed all fully automated server submissions. Hopefully over time foldit can do even better, but being able to produce solutions of same quality as experts means that the top science research can now also be done outside of labs by game players, significantly speeding up the process of scientific advancement! "
- Michael Nielsen
Naturally occurring deuterium is essential for the normal growth rate of cells... [FEBS Lett. 1993] - PubMed result - http://www.ncbi.nlm.nih.gov.li...
The role of naturally occurring D in living organisms has been examined by using deuterium-depleted water (30-40 ppm D) instead of water containing the natural abundance of D (150 ppm). The deuterium-depleted water significantly decreased the growth rate of the L929 fibroblast cell line, and also inhibited the tumor growth in xenotransplanted mice. Eighty days after transplantation in 10 (59%) out of 17 tumorous mice the tumor, after having grown, regressed and then disappeared. We suggest that the naturally occurring D has a central role in signal transduction involved in cell cycle regulation.
- Steve Koch
This is one of those papers you have to read (and while you're reading it, I'm patenting my deuterium-depletion filter for home use and sending the press release to the daily mail, national enquirer, and Oprah).
- Mr. Gunn
I haven't read it yet. Are you hinting that it's good or bad?
- Steve Koch
Not having read it, it could be that whatever they're doing to deplete the deuterium is leaving some harmful stuff in the water, and that certainly sounds more likely, but one would think the editorial process would weed out such obvious mistakes, but mistakes do happen and I've seen some crazy stuff come out of eastern european labs and the related articles are also all kinda obscure, but prions and transposons were once thought to be crazy fringe ideas too...
- Mr. Gunn
Well, you may be onto something. In methods, they say, "Deuterium-depleted water (30-40 ppm D) was obtained from tap water (150 ppm) by electrolysis," ... Seems a bit sketchy to use tap water, even in 1993. ... All that aside, I've been a quite surprised this weekend at how drastically D versus H can change the chemistry of things. I'd been inappropriately biased towards thinking the...
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- Steve Koch
Steve, could you give an example of a case where D versus H is known to change the chemistry? I, too, had (have) the bias you mention.
- mkz
@mkz, there're some general examples at wikipedia "kinetic isotope effect" http://en.wikipedia.org/wiki... ... There are also reports that heavy water tastes differently than H2O (can't find link now), which would most likely be chemistry (right?). The strong toxicity of heavy water to eukaryotic cells also argues for chemical effects. I guess I don't know the best example.
- Steve Koch
A grad student in our lab, Andy Maloney, did a kinesin motility assay in heavy water on Friday and saw an amazing array of cool effects (http://openwetware.org/wiki...) ... At this point, is tough to figure out the science, but it's nevertheless very exciting. One thing we want to try is to compare D2O to...
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- Steve Koch
Wow, I didn't know heavy water was toxic. I figured the vibrational spectra would change when you change the isotope, and guessed minor changes in molecular structure could similarly occur, but it seems the effects are much more pronounced than that.
- mkz
Those experiments look interesting! (Not that I know much about the field.) D2O versus H2(O18) sounds like an interesting experiment, too, hopefully we'll be able to follow the results here.
- mkz
I know, amazing, huh? (heavy water toxicity) The funny thing is I was thinking D2O would be a simpler way of probing water activity, compared with osmotic stress. Ha!
- Steve Koch
As for the experiments, Andy is an Open Notebook Science (ONS) practitioner, so all his results (as of now) will be available. It's actually been a conundrum for me this weekend as to whether or not to advertise his results. A good case study in ONS--on the one hand, I'm super-excited. On the other hand, we don't know what's going on, and I feel like he may prefer some time to figure some things out. Who knows? Glad you liked his experiments!
- Steve Koch
@mkz, I put some thoughts on Andy's notebook's "talk" page here: http://openwetware.org/wiki... I was amazed to find out they actually use D2O to stabilize proteins in vaccines.
- Steve Koch
It is indeed a good case study in ONS, I'm happy to hear the results will be available, but I'd understand if you guys changed your minds. I'm not sure how open I could bring myself to be when I make a discovery, waiting to be explained/utilized. Good luck with the project.
- mkz
Just looked at your comments, reading that page was fun (and heavy water ice sinks in water?--nice).
- mkz
Good night, and thanks for your thoughts!
- Steve Koch
Steve the videos on Andy's page you link to look awesome but I'm not sure I understand exactly what was done - is there a section with the experimental details or is that what you guys are debating whether or not to release?
- Jean-Claude Bradley
@Jean-Claude: What specifics would you like to know? I'm still in the process of making my experimental procedure available on OWW of which I will link to in my notebook. So, I apologize if things are still in disarray when it comes to the specifics of how I do things.
- Andy Maloney
There's no debate on releasing anything--all info is desired to be public. In fact, there's no debate at all except in my own mind--as to whether to specifically invite people to look at the results (which I did above) via a blog post or other. @Andy, I think what Jean-Claude is saying is that it's very much not evident what your experimental methods are, mostly because of the...
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- Steve Koch
Andy - I was looking for which materials and in what amounts were added at what times to understand the videos and the effect of the deuterium. I'm intrigued by the effect of isotopes in chemical processes and I think your experiments could yield valuable insight. We've also very briefly looked at the effect of deuteration on smell http://usefulchem.wikispaces.com/Exp218 because of the putative detection of molecular vibration in receptors
- Jean-Claude Bradley
It's worth noting that most commercial D2O is pretty filthy from a colloid chemistry perspective. Strictly speaking ultrafiltration or reverse osmosis is required to get to the kind of water quality one routinely expects these days for the normal stuff. But it's way too expensive to blow 10 L of D2O on getting a water purifier fully exchanged...
- Cameron Neylon
Jean-Claude: Yep, this is going to take a while to clean up and do what you ask. I'm really motivated right now to start an experiment so, I will have to come back to this later tonight. I'll let you know when I have a draft for a materials and procedure page.
- Andy Maloney
from a completely different perspective, then it wouldn't be a good idea to use a D20 moisture mist? The latest thing in cosmetics: http://snipurl.com/t0vih
- Mickey Schafer
@Jean-Claude, cool smell experiment! (Is row 2A mislabeled, or am I misreading?) I've been wanting to try some kind of isotopic smell thing ever since reading the Turin book.
- Steve Koch
@Cameron thanks for that tip. We're keeping it in mind now that the results could be attributable to contaminants. Question: It's definitely too expensive for us to think of doing that. But wouldn't Sigma be able to afford doing so?
- Steve Koch
Steve - thanks yest that was a mislabeling and it is fixed now - although note that (as indicated in the conclusion) the results in the table are not meaningful. Designing a statistically valid test like this is harder than it might seem and would require many more samples. The best I would hope from this experiment is to motivate a few more researchers to take a few minutes and sniff -...
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- Jean-Claude Bradley
Thanks Andy - I'm not asking to write a full report. It is probably enough to just post the experimental notes. In our lab that would correspond to the "log" section, whereas the full well formatted report is the "procedure" section to be written later. (e.g. http://onschallenge.wikispaces.com/Exp130 ). If that isn't how you keep track of experiments could you let me know what...
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- Jean-Claude Bradley
Hey Jean-Claude, Interesting smell reference in a review I'm reading: "2.5.1. Olfaction in fish. Hara [40] investigated the ability of the whitefish, Coregonus clupeaformis, to distinguish between the odor of glycine (Gly) and fully deuterated glycine (Gly-ds). Over the concentration range of 10^-8 to 10^-4 M, these fish avoided solutions of Gly-ds and preferred solutions of Gly." From:...
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- Steve Koch
California LLC's beware, we just were hit by the fraudulent Business Filings Division scam demanding we pay them $239 http://laughingsquid.com/beware-...
Doesn't this put your Aussie Man Card in jeopardy? All the Aussie blokes we see in movies and on TV do not get chased up anything, unless it's by at least a 60-foot long Croc :) Did the Koala look like a 60 foot croc when you first spotted him?
- Patrick Jordan
You should keep some eucalyptus leaves handy to throw them off your trails.
- Pete Delucchi
from iPhone
so Australia is living up to the fantasy I have of it in my head, built from movies in the 80s like A Town Called Alice and Thorn Birds. NICE.
- anna sauce
It was Bruce. He is the dominant male in our area. I got out of the car and I heard some rustling from the trees. When I started to walk up the path, I saw him climb down and start walking towards me. He grunted very aggressively, something I don't want to stick around for so I bolted. I must have disturbed him having a root with one of his girlfriends.
- Johnny Worthington
yes, Johnny certainly knows how to paint a word picture...!
- WorldofHiglet
this just proves the value of that welcome mat my mom used to have: 'Friends Welcome. Family - Make Reservations'. Maybe the little guy thought you were a distant cousin, and decided to relight the fire under the long standing family feud between the Worthingtons and the Koalas?
- Morgan Haley
Bruce is totally going to lose his endorsement deal with Qantas
- Spidra Webster
Does anyone know of any MapReduce implementations of sequence motif finding algorithms? If not, what would be a suitable open-source motif finding package that could potentially be mapreducified? And are there any Amazon Machine Images with preinstalled motif finding packages?
The rapid shift of the microbial population back to the anaerobic state following ileostomy closing is interesting in itself, but it's the clinical relevance that can't be ignored. Great science and study.
- Mark Strom
BMC Genomics, Vol. 10, No. 1. (2009), 431. BACKGROUND:MicroRNAs (miRNAs) are endogenous small RNA molecules that modulate the gene expression at the post-transcription levels in many eukaryotic cells. Their widespread and important role in animals is gauged by estimates that ~25% of all genes are miRNA targets. RESULTS:We perform a systematic investigation of the relationship between miRNA regulation and their targets' evolution in two mammals: human and mouse. We find genes with longer 3' UTRs are regulated by more distinct types of miRNAs. These genes correspondingly tend to have slower evolutionary rates at the protein level. Housekeeping genes are another class of genes that evolve slowly. However, they have a distinctly different type of regulation, with shorter 3'UTRs to avoid miRNA targeting. CONCLUSIONS:Our analysis suggests a two-way evolutionary mechanism for miRNA targets on the basis of their cellular roles and the length of their 3' UTRs. Functionally critical genes that...
- Neil Saunders
Nature, Vol. 461, No. 7261. (26 August 2009), pp. 258-262. Cyanobacteria of the Synechococcus and Prochlorococcus genera are important contributors to photosynthetic productivity in the open oceans1, 2, 3. Recently, core photosystem II (PSII) genes were identified in cyanophages and proposed to function in photosynthesis and in increasing viral fitness by supplementing the host production of these proteins4, 5, 6, 7. Here we show evidence for the presence of photosystem I (PSI) genes in the genomes of viruses that infect these marine cyanobacteria, using pre-existing metagenomic data from the global ocean sampling expedition8 as well as from viral biomes9. The seven cyanobacterial core PSI genes identified in this study, psaA, B, C, D, E, K and a unique J and F fusion, form a cluster in cyanophage genomes, suggestive of selection for a distinct function in the virus life cycle. The existence of this PSI cluster was confirmed with overlapping and long polymerase chain reaction on...
- Neil Saunders
Nature, Vol. 461, No. 7260. (3 September 2009), pp. 114-119. TRAF6 is a ubiquitin ligase that is essential for the activation of NF-ºB and MAP kinases in several signalling pathways, including those emanating from the interleukin 1 and Toll-like receptors. TRAF6 functions together with a ubiquitin-conjugating enzyme complex consisting of UBC13 (also known as UBE2N) and UEV1A (UBE2V1) to catalyse Lys 63-linked polyubiquitination, which activates the TAK1 (also known as MAP3K7) kinase complex. TAK1 in turn phosphorylates and activates IºB kinase (IKK), leading to the activation of NF-ºB. Although several proteins are known to be polyubiquitinated in the IL1R and Toll-like receptor pathways, it is not clear whether ubiquitination of any of these proteins is important for TAK1 or IKK activation. By reconstituting TAK1 activation in vitro using purified proteins, here we show that free Lys 63 polyubiquitin chains, which are not conjugated to any target protein, directly activate TAK1 by...
- Neil Saunders
Oh great. Ubiquitination network gets even more complex. Just what my poor brain needs. :-)
- Bill Hooker
Tracing the evolution of a large protein complex in the eukaryotes, NADH:ubiquinone oxidoreductase (Complex I). - http://www.ncbi.nlm.nih.gov/pubmed...
The mrFAST algorithm has three major goals: first, to map large amounts of next-generation (short-read) sequence data to the reference genome; second, to determine the depth of reads across the genome; and finally, to identifying single nucleotide polymorphisms (SNPs) across the genome, including duplicated regions.
- Abhishek Tiwari
from Bookmarklet
Completely unrelated, but I sometimes wonder how much software/protein/protocol names are motivated by "wouldn't it be cool if our algorithm was called Mr. Fast!?"
- Benjamin Tseng
Benjamin that true although in this case mrFAST stands for “micro-read Fast Alignment Search Tool”
- Abhishek Tiwari
Proteins: Structure, Function, and Bioinformatics, Vol. 9999, No. 9999. (2009), NA. Ubiquitination plays an important role in many cellular processes and is implicated in many diseases. Experimental identification of ubiquitination sites is challenging due to rapid turnover of ubiquitinated proteins and the large size of the ubiquitin modifier. We identified 141 new ubiquitination sites using a combination of liquid chromatography, mass spectrometry, and mutant yeast strains. Investigation of the sequence biases and structural preferences around known ubiquitination sites indicated that their properties were similar to those of intrinsically disordered protein regions. Using a combined set of new and previously known ubiquitination sites, we developed a random forest predictor of ubiquitination sites, UbPred. The class-balanced accuracy of UbPred reached 72%, with the area under the ROC curve at 80%. The application of UbPred showed that high confidence Rsp5 ubiquitin ligase...
- Neil Saunders