The DNA Network |
| Creationists Love Baseball [evolgen] Posted: 17 Jul 2008 07:15 PM CDT
The Creation Museum is located in northern Kentucky, just across the Ohio border from Cincinnati. Answers in Genesis, the folks behind the so-called "museum", claim that their "museum" is within a 6 hour drive of 2/3 of the US population. This is not true -- Kentucky is in the middle of bumfuck nowhere (I'm an expert on cities in the middle of bumfuck nowhere), and most people in the US can't get there in 6 hours. But the museum is damn close to Cincinnati -- it's in what people would call the "greater Cincinnati area", and it's closer to the so-called Cincinnati airport (which is actually in Kentucky) than the airport is to Cincinatti. Anyway, it's so close to Cincinnati (how close is it?) that Answers in Genesis is advertising their "museum" on during what can be considered the most important event in all of Cincinnati: the broadcast of their beloved Reds' games (Reds think evolution is for suckers). If you listen to the local baseball team on the radio, you're going to hear about the Creation Museum. Now, here's where it all comes full circle. You see, one the greatest Reds of all time, Joe Morgan, also happens to be an absolute ignoramus when it comes to baseball (Hey, Bob. You remember the other day, you asked me what the definition of "irony" was...). I've previously dubbed him the baseball creationist. Well, it appears that the Reds are going back to their roots by advertising the Creation Museum on their broadcast -- reaching out to Little Joe in the way a bunch of ignorant fucktards only know how. Read the comments on this post... |
| DNA Test Confirms Remains of the Last of the Russian Tsar’s Family [The DNA Testing Blog] Posted: 17 Jul 2008 04:07 PM CDT Russian authorities confirmed yesterday that the bone fragments found last year belonged to Alexei and Maria, the last two members of the Romanov family whose fates remained in question. The rest of the royal family’s remains were found in 1991 at a burial site in Yekaterinburg, Siberia. Historical accounts say that on July 17, 1918, Communist guards [...] |
| How the Taliban is Bringing Back Polio [Epidemix] Posted: 17 Jul 2008 02:50 PM CDT On a NYTimes blog, a harrowing tale of the conflict between religious extremism and the WHO in Pakistan. Fearful that the polio vaccine causes impotence (it doesn’t), local clerics in northern Pakistan waged a campaign against the vaccine, and Unicef called off its immunization effort. The result: The first case of polio in the area since 2003. Some fascinating overlaps with the war against the Taliban in the area. Worth a read - and a longer exploration by someone. |
| Notes from Kindergarten [The Daily Transcript] Posted: 17 Jul 2008 02:41 PM CDT A friend of mine just sent this to me (for the record, he's a structure biologist, i.e. he studies the structure of proteins and other biological molecules): My kid had a screen session with a school administrator for his kindergarten today. Following are some answers he came up with:Read the comments on this post... |
| America: Now Fatter than Ever [Epidemix] Posted: 17 Jul 2008 01:24 PM CDT
And note that’s obese, not overweight: when you include those numbers, defined as a BMI greater than 25, the percentage approaches two-thirds of all American adults. The map itself paints a dramatic picture. I’ve stuck the new 2007 map below of the previous version from 2005, and you can see the slow creep of fat across the nation.
So much for Healthy People 2010, an effort by the CDC, started back in 2000, to get the country towards 15% adult obesity rate. I’ve been skeptical in the past of efforts to treat obesity as a disease; it seems just the sort of lifestyle condition that creeping medicalization doesn’t need to sweep up. But these stats are changing my mind: We Americans just can’t seem to stop eating. Whatever’s going on - genetically, environmentally, metabolically - it’s not something finger-wagging and brochures can take care of. What’s more, this is going to be *extremely* expensive. I think it’s high time somebody came up with some innovative behavior-modification strategies, short of pharmaceuticals, that might start to turn this tide. More on that later. |
| Closed Access Award #1: American Psychological Association [The Tree of Life] Posted: 17 Jul 2008 12:02 PM CDT Well, I wrote up this award a short time ago and already the story has changed. But I am still giving the award. On Tuesday, Peter Suber reported that I agree with Peter that this is a stunningly inane move on their part (for more discussion see Suber's follow up here). They are basically saying that to carry out a simply electronic submission they will charge $2500. Apparently someone convinced them this was not the brightest thing in the world to do as they are now reconsidering this move (I learned about this reconsideration from the Scientist magazine blog here ... you need to register to read the blog). This blog reports A statement sent to The Scientist today from APA Publisher Gary VandenBos said: "A new document deposit policy...is currently being re-examined and will not be implemented at this time...APA will soon be releasing more detailed information about the complex issues involved in the implementation of the new NIH Public Access Policy."Even though they are reconsidering their policy, since they have not out and out rescinded it, I am still giving the American Psychological Association my first "Closed Access Award" for this incredibly silly move |
| Another tradeoff in order to avoid malaria? [Yann Klimentidis' Weblog] Posted: 17 Jul 2008 10:48 AM CDT
I assume and hope that they control for population stratification when they find that the "DARC −46C/C is associated with 40% increase in the odds of acquiring HIV-1" Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility Weijing He, Stuart Neil, Hemant Kulkarni, Edward Wright, Brian K. Agan, Vincent C. Marconi, Matthew J. Dolan, Robin A. Weiss, and Sunil K. Ahuja Cell Host and Microbe Volume 4, Issue 1, 17 July 2008, Pages 52-62 Abstract: Duffy antigen receptor for chemokines (DARC) expressed on red blood cells (RBCs) influences plasma levels of HIV-1-suppressive and proinflammatory chemokines such as CCL5/RANTES. DARC is also the RBC receptor for Plasmodium vivax. Africans with DARC −46C/C genotype, which confers a DARC-negative phenotype, are resistant to vivax malaria. Here, we show that HIV-1 attaches to RBCs via DARC, effecting trans-infection of target cells. In African Americans, DARC −46C/C is associated with 40% increase in the odds of acquiring HIV-1. If extrapolated to Africans, 11% of the HIV-1 burden in Africa may be linked to this genotype. After infection occurs, however, DARC-negative RBC status is associated with slower disease progression. Furthermore, the disease-accelerating effect of a previously described CCL5 polymorphism is evident only in DARC-expressing and not in DARC-negative HIV-infected individuals. Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation. |
| How To Get The Best cDNA For Gene Isolation [Bitesize Bio] Posted: 17 Jul 2008 09:55 AM CDT cDNA (complementary DNA) is an extremely useful tool - gifted to molecular biologists by RNA viruses, which fortunately “invented” the reverse transcriptase enzyme that allows us to make the stuff. RNA viruses use this mRNA dependent DNA polymerase to convert their single-stranded genome into double-stranded DNA for integration in their host’s genome. But in the lab, it can be harnessed to make cDNA copies from mRNA templates. That means that reverse transcriptase can be used synthesize a cDNA copy of every mRNA that is present in an mRNA extract, and that’s a pretty useful thing to be able to do. Because from those cDNA copies you can do things like PCR amplify agene of interest, or make a cDNA library and probe it for a specific sequence or activity. There are several advantages to using cDNA as opposed to genomic DNA for doing this: • No introns: Eukaryote genes commonly contain introns (non-coding sequences). These are removed after mRNA synthesis so cDNA contains no introns. This means that a cDNA copy of a gene can be isolated as a single, intron-free fragment. Prokaryotes don’t have introns so this is not a problem if you are working with bacterial genes. That’s the basics but for the rest of this article I’ll be focusing on a topic that might concern those of you who need to isolate genes with tissue-specific expression profiles. For this you need to synthesize cDNA from the entire mRNA complement of your tissue of choice then use this as a template to amplify your target gene. But how do you choose the right tissue to isolate your cDNA from? I’ll tell you how. Get it wrong and you could have to re-think your strategy - I’ll tell you how to do that too. How to choose a good source for making your cDNA library The mRNA used to make cDNA is extracted from different tissues of the body (eg. brain, kidney, liver) or less commonly from cultured cells (eg. HeLa cells). cDNA represents the pool of genes expressed in a tissue and given that every organ has a different function in the body, each tissue has different expression levels of each gene. So with so many tissues to choose from, what is the best tissue cDNA to use for isolating your gene? The short answer is the one that has highest level of expression of your gene. The more abundantly the gene is expressed in the tissue, the more likely you will isolate your gene by PCR because there is more template to amplify from. The best way to find out where your gene is expressed best is to read the paper/s that first characterized the gene. These almost always contain the tissue distribution or expression profile of the gene because this is one of the first logical studies to perform when a new gene is discovered. These papers (or at least references to these papers) can usually be found on the NCBI and Swiss-Prot websites. There are several sources of information on the expression profile of a gene but the best source is always the original data so you can make a decision on what the true expression levels of the gene. Have a go at the PCR So you’ve chosen your candidate tissue and made the Once a suitable cDNA has been chosen, give it a shot! It's always good to try more than one cDNA if you can because then if one tissue fails the others may produce the desired band or more of it if you're lucky! If you don’t get the required band, first try optimizing the PCR reaction itself. Additives like betaine might help and so might this PCR troubleshooting checklist, but If this doesn’t yield results - what next? Add more cDNA template The most common reason for unsuccessful isolation of a target from cDNA is that the cDNA does not contain enough of the target for successful amplification. Adding more template to increase the concentration of the target often works but usually a new cDNA is the approach that needs to be taken. If this does not work, it could mean that your target gene is expressed poorly, or even not at all, in the tissue you selected so… Try a more specific tissue One trick for isolating difficult targets is to use a cDNA from a more specific region of the tissue you used. If you think about it, an organ (eg. brain) is made of several functional parts (eg. hippocampus, pituitary, hypothalamus) and the expression of a gene in a whole cDNA is just the average expression of all the parts of that organ. Intuitively then, there is always going to be more specific part of the organ that has a higher expression of your gene. Finding expression data on more specific areas of a tissue or even finding commercially available sources of specific areas of an organ can be difficult. Certain organs such as the brain often have good expression data and tissue availability on different parts of the organ but even if there is no expression data and more specific areas are available it is often worth trying more specific areas and you may be pleasantly surprised. But what if this fails too? Fear not, there are still other avenues to pursue. Try a related tissue Another approach is to try a "related" tissue, as I like to call it. One time I had a gene that was meant to be expressed in the brain but I couldn't isolate it from the brain or other more specific areas. So I used a "related" tissue, namely retina cDNA, because the eye/retina, much like the brain, is mainly nervous tissue. Low and behold, I got a lovely band from retina cDNA. Most examples of "related" tissues fall into the category of "systems" relatedness. Below is a list of tissues that are part of different systems that could be used for isolating your target: • circulatory – bone marrow, peripheral blood leukocytes (PBLs), heart, spleen, thymus If there are too many tissues to try at once, pool the cDNAs into one reaction. The purpose of pooling cDNA is to reduce the number of reactions that needs to be performed. If you are going to pool cDNA however, make sure that you do not dilute each cDNA. Rather, add as much of each cDNA in the pooled reaction as you would in a single reaction. This ensures the target in abundant tissues is not diluted, which compromises the success of the reaction. In the absence of expression data or poor success with other cDNAs, potential sources of a gene can also be determined by the function of the gene. For example, if a gene is a receptor known to be activated by glutamate (a neurotransmitter), then that gene is most likely going to be found in the brain. Likewise, if a mutation in a gene has been associated with increased risk of diabetes, then the pancreas or adipose tissue may be good tissues to try. If a related tissue doesn’t give you the result you are looking for then there’s one more possibility… Get your (boss’?) credit card out If none of the above works, then you may have exhausted your options with regards to cDNA. The next step would probably be to look into buying a commercial clone. Whilst this is considerably more expensive than cDNA, you're virtually guaranteed to isolate your target. What are your experiences isolating genes from cDNA libraries? Photo: Wikimedia |
| Posted: 17 Jul 2008 08:00 AM CDT Olivia Judson says Darwinism is dead. She's right. Anyone who talks about "Darwinism" or "evolutionists" gets my attention. That's not to say that any use of those terms is incorrect. But they are often used as framing devices by creationists, and those frames get carried over into the lay discussion of biology. You should read her discussion of why we should get rid of Darwinism. On a somewhat unrelated note, Judson also writes the following:
Natural selection is not creative. It acts on variation that is created by mutation. That makes mutation the only creative force. Natural selection, like all other forces besides mutation, can produce complex structures (yes, complexity can be produce by entirely neutral processes). But, without mutation, there is no new variation upon which those forces can act. Read the comments on this post... |
| Hello from New Haven [Think Gene] Posted: 17 Jul 2008 02:02 AM CDT Thinkgene is on the road this week. Regular postings will resume next week. |
| Forging into the gap [Omics! Omics!] Posted: 16 Jul 2008 10:27 PM CDT Gaps are important. There is a major brand by that name. Controversy over a perceived "missle gap" was a major issue in the Nixon-Kennedy election of 1960. Budget gaps cause governments to trim services. About a half an hour's drive west of where I grew up is the town of Gap, and a bunch of generations ago my ancestors probably passed through the Cumberland Gap. Gaps occupy a special place in computational biology, specifically in the alignment of sequences and structures. As sequences evolve, they can acquire new residues (insertions) or lose residues (deletions), and so if we wish to align a pair of sequences we must put a gap in. Pairwise algorithms such as Needleman-Wunsch-Sellers and Smith-Waterman insert the optimal gaps -- given certain assumptions which include, but are not limited to, the match, mismatch, gap insertion and gap deletion penalties. Some pairwise alignment problems have been addressed by even more complicated gapping schemes. For example, if I am aligning a cDNA to a genomic sequence I may wish to have separate consideration of introns (a special case of gaps), gaps that would insert or remove multiples of three (codons) or gaps which don't all in either of those categories. Multiple sequence alignment gets even harder. There are no exact algorithms to compute a guaranteed best alignment, so all methods have some degree of heuristics to them. Many algorithms are progressive, first aligning two sequences and then aligning another to that alignment and then another and so on, or perhaps aligning pairs of sequences and then aligning the aligned pairs and so on. Placement of gaps becomes especially tricky, as their placement in early alignments greatly influences the placement in later alignments, which could well be a bad thing. Protein alignments in particular have the problem of trying to serve three masters, who are often but not always in agreement. An alignment can be a hypothesis of which parts of a protein serve the same role, a hypothesis as to which amino acids occupy similar positions in space, or a hypothesis as to which amino acids derive from codons with a shared ancestry. Particularly in the strongly conserved core of proteins these three are likely to be in agreement, but in the hinterlands of structural loops in proteins or disordered regions it's not so clear. There is also a bit of aesthetics that comes in; alignments just look neater and simpler when there are fewer gaps. Perhaps not quite Occam's Razor in action, but simplicity is appealing. The June 20th issue of Science (yep, Science & Nature have been piling up) has a paper that addresses this issue and builds an algorithm unapologetically aligned to just the one goal: find the most plausible evolutionary history. They point out that while insertions and deletions are treated symmetrically by pairwise programs, they are quite asymmetric for progressive multiple alignment. The alignment gets to pay once for deleting something, but insertions (like overdue credit cards) incur a penalty with each successive alignment. It seems unlikely that nature works the same way, so this is undesirable. One solution to this has been to have site-specific insertion penalties. Loytnoja & Goldman point out that this compensation often doesn't work and causes insertions to be aligned which are not homologous, in the sense that they each arose from a different event (indeed, these insertions should not be aligned with anything from an evolutionary point-of-view, though structurally or functionally an alignment is reasonable). As an alternative, their method flags insertions made in early alignments so that they are treated specially in later alignments. The flagging scheme even allows insertions at the same position to be treated as independent -- they neither help nor penalize the alignment and are reported as separate entities. Using synthetic data they tested their program against a number of other popular multiple aligners and found (surprise!) it did a better job of created the correct alignment. They also simulated what getting additional, intermediate data does for the alignments -- and scarily for the older alignment programs gap placement got worse (less reflective of the actual insertion/deletion history of the synthetic data). The article closes with an interesting question: has our view of sequence evolution been shaped by incorrect algorithms? Is the dominant driver of sequence change in protein loops point mutants or small insertions/deletions. Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis Ari Löytynoja and Nick Goldman http://www.sciencemag.org/cgi/content/abstract/320/5883/1632 p. 1632 |
| 1rst anniversary wordle cloud [biomarker-driven mental health 2.0] Posted: 16 Jul 2008 09:35 PM CDT |
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