The DNA Network

Obama on Teaching Evolution [The Tree of Life]

Posted: 16 Jun 2008 07:54 PM CDT

I finally found what appears to be a credible reference to Obama's views on teaching evolution. In an April Blog from the Dallas Morning News they quote the York Daily Record:

He was asked about the teaching of intelligent design and evolution in public schools.

His response:

I'm a Christian, and I believe in parents being able to provide children with religious instruction without interference from the state.
But I also believe our schools are there to teach worldly knowledge and science. I believe in evolution, and I believe there's a difference between science and faith. That doesn't make faith any less important than science.

It just means they're two different things. And I think it's a mistake to try to cloud the teaching of science with theories that frankly don't hold up to scientific inquiry.

McCain seems to have gone silent on this issue although I have pointed out that in the past that he was clear about science being taught in science classes. Seems like he is trying to steer clear of this issue. What ever happened to the straight talking McCain?

Growth in commercial disease gene tests [Genetic Future]

Posted: 16 Jun 2008 07:28 PM CDT

From GeneTests, via OpenHelix:

That's pretty impressive, but just wait: within the year, next-generation sequencing will make it commercially viable to sequence thousands of genes at once; and a year or two after that it will be more cost-effective to just sequence the entire genome and be done with it, effectively maxing out the curve at the level of "every disease for which the causative genes are known". After that, the rate of growth in the curve will be determined by the rate at which new disease genes can be discovered and characterised.

You can see that the number of testing laboratories is already plateauing - it will be interesting to see how quickly this declines over the next few years as large sequencing-based companies either engulf the boutique specialist laboratories or drive them out of business. There are ruthless economies of scale in the human disease genomics business, both in terms of sequencing infrastructure and the costs of assembling reliable knowledge bases for interpretation, so it will be increasingly difficult for smaller companies to stay competitive.

Subscribe to Genetic Future.

Connotea, you’ve been good to me [Synthesis]

Posted: 16 Jun 2008 06:05 PM CDT

Despite all that, you’ve been a little slow lately, and I found my thoughts wandering. Earlier today, I noticed a 2collab link, and, without thinking about it, clicked over to see what has changed since last time we met. Before I knew it, I was pulling in my publications via Scopus ID, tagging papers, and joining interest groups. I’m sorry, Connotea, but the speed was just so intoxicating that I went and exported my whole library from you and went to import it to 2collab. It seems my affections weren’t returned, however, as I was slapped with the following message:

Unable to import bookmarks: org.hibernate.exception.ConstraintViolationException: Could not execute JDBC batch update

Like a bucket of cold water, that returned me to my senses, and I came back to you, ol’ Buggotea.

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This post is about 2collab, connotea, fail

Drug Interactions of Oral Contraceptives [A Forum for Improving Drug Safety]

Posted: 16 Jun 2008 05:55 PM CDT

COMMENT:
The drug interactions of oral contraceptives (OCs) are quite complex. They are both a victim to CYP3A4 inducers- leading to possible reduction of ethinyl estradiol concentration and pregnancy and to CYP3A inhibitors– leading to increased adverse effects. The ethinyl estradiol component of OCs has been shown to be P450 cytochromal inhibitors of CYP2C9, CYP2C19, CYP2B6, intestinal CYP3A4 and CYP1A2. Melatonin, a substrate of CYP1A2, is a commonly used non-prescription hypnotic. This study shows that with co- administration of OCs and melatonin, the CMax of melatonin was increased 4-5 fold and that it is likely that melatonin’s therapeutic index is wide since there was no increased sleepiness.

Although this DDI is likely of little clinical significance, it does remind clinicians to the possibility of more significant drug interactions with OCs combined with CYP1A2 substrates, such as clozapine, fluvoxamine, chlorpromazine, cyclobenzaprine, flutamide, ropinirole and others, some of which have had cases already reported in the literature. It is an exercise in rational prediction to assume that some women on OCs will have increased adverse effects with CYP1A2 substrates.

ABSTRACT: J Clin Pharmacol. 2008 May 19. [Epub ahead of print] The Effect of Oral Contraceptives on the Pharmacokinetics of Melatonin in Healthy Subjects With CYP1A2 g.-163C>A Polymorphism Hilli J, Korhonen T, Turpeinen M, Hokkanen J, Mattila S, Laine K.

The effect of oral contraceptives (OCs) on melatonin metabolism was studied in 29 subjects genotyped for CYP1A2 SNP g.-163C>A polymorphism. Plasma melatonin and 6-OH-melatonin concentrations were measured after a 6-mg dose of melatonin using a validated liquid chromatography/mass spectrometry method. The mean melatonin AUC and Cmax values were 4- to 5-fold higher in OC users than in non-OC users (P < .0001), whereas the weight-adjusted clearance was significantly lower in OC users (P < .0001). No significant difference in melatonin pharmacokinetics between the genotypes and no additional effect by the genotype on the OC-induced increase in melatonin exposure were evident. Melatonin exposure had no significant effect on the subjects’ state of alertness. In conclusion, a significant inhibitory effect of OCs on the CYP1A2-catalyzed melatonin metabolism was seen; thereby, OC use can alter CYP1A2-phenotyping results.

Sweet Light Green Crude []

Posted: 16 Jun 2008 04:44 PM CDT

Newsday reports that San Diego-based Sapphire Energy claims to be able to produce transgenic algae-based “Green Crude” yielding ultra-clean chemically equivalent versions of gasoline and diesel without the usual downsides of biofuel production. Their process uses algae, sunlight, carbon dioxide and non-potable water. Sapphire says green crude can be processed in existing oil refineries — a green plug-in for the the existing oil industry processing and refining infrastructure. We hope it’s for real.

With profound apologies to The Eagles… [genomeboy.com]

Posted: 16 Jun 2008 04:29 PM CDT

On a dark coastal highway, nucleic acid in my hair
Warm smell of venture capital, rising up through the air
Up ahead in the distance, I saw blood, spit and sperm
My head grew heavy and my wallet grew light
I had to start a firm

There she stood in the lab bay;
Loading an agarose gel
And I was thinking to myself,
'This could be DNA or this could be cells'
Then she lit up a lightbox and she showed me the way
There were voices on the conference call,
I thought I heard them say…

Welcome to the Hotel Varioma
Such a competitive race
Such a competitive space
Plenty of room at the Hotel Varioma
Every fiscal year, you can find it here

Her tree is ancestry-twisted, Affy she aided and abetted
She got a lot of discrete, discreet traits, that she calls vetted
How they drool in the test tubes, sweet summer spit
Some drool to empower, some drool to transmit

So I called up the FDA,
'Please give me a sign'
They said, 'We haven't had that spirit here since nineteen ninety-nine,'
And still enforcement discretion is far away,
Shut you down in the middle of the night
Before you hear them say…

Welcome to the Hotel Varioma
Such a competitive race
Such a competitive space
Plenty of room at the Hotel Varioma
What a Judas kiss, better cease and desist

Genotypes we’re revealing,
Your DNA’s on ice
And she said 'This is all just home brew here, it’s not a medical device'
And in the judge's chambers,
They gathered for the meal
They slap it with their regulations,
But they just can't close the deal

Last thing I remember, I was
Checking my results
I had to find the passage back
To the world of consenting adults
'Relax,' said the house doc,
‘We are programmed to protest.
You can market anywhere you like,
But you can never test!’

Mary Meets Dolly on the radio [Mary Meets Dolly]

Posted: 16 Jun 2008 04:00 PM CDT

Apparently, I will be on Sacred Heart Radio Cincinnati tomorrow at 8:40 EST being interviewed by Brian Patrick. They have a Listen Live link on their website. If you are awake you might want to check it out.

From Virtuality to Reality: Second Life Fitness [ScienceRoll]

Posted: 16 Jun 2008 03:47 PM CDT

How could we combine the opportunities of Second Life, the virtual world, with the advantages of reality? Check out Second Life Fitness. You need something like this:

And it leads to this:

If you ride the bike, you can fly in Second Life. There are currently 54 users (with a total distance of 974 km).

Isn’t it a fantastic idea?

More about Second Life:

How much is that doggy in the window? [Discovering Biology in a Digital World]

Posted: 16 Jun 2008 03:30 PM CDT

Pet cloning is back!

Pets are funny things. Some owners find their pets to be closer than some human friends, other owners never really bond with their pets at all.

BioArts, a California biotech company, founded by ex-CEO of the now defunct Genetic Savings & Clone, is counting on the strength of those human-dog emotional bonds .

Read the rest of this post... | Read the comments on this post...

QBlossoc [Mailund on the Internet]

Posted: 16 Jun 2008 02:29 PM CDT

I’ve just made a release of our association mapping tool, Blossoc. The new release, nicknamed QBlossoc, adds full support for quantitative phenotypes. We’ve had support for quantitative phenotypes for a while now, but this version is the “official” release for it, with tuned default options and such.

It is mainly the work of Søren Besenbacher, who’s been running simulation experiments for the last several months to figure out which scoring methods, and with which parameters, works best.

Although the quantitative traits method hasn’t been published yet — we only submitted the paper last week — it has already been used by Monica Ledur et al. to analyse the data set from the XII QTLMAS workshop in Uppsala. There should be a paper coming out on that as well. I don’t know its status, but Monica was kind enough to send the manuscript to me.

Updates on the CCRG and C-51 [Bayblab]

Posted: 16 Jun 2008 01:19 PM CDT

We received the following email from a reader, updating us on some goings-on with respect to Bill O'Neill and the Canadian Cancer Research Group as well as Bill C-51. [Links added]

Hi, Bayblab . . .
I took an interest in Bayblab as soon as I learned that Bill O'Neill (CCRG, ISM) threatened to sue you. That put you in very distinguished company.

Here are some fairly recent developments on the CCRG, ISM scene, most of which you likely already know about:

-- Immune System Management, ISM, has been granted 'corporate membership' in OCRI.

-- Bill seems to be switching the emphasis from his CCRG to his ISM: The directory board inside the Fifth Avenue Court building still lists the CCRG as a tenant, but the sign swinging above the entrance to Bill's offices that once read "CCRG" has been replaced with one reading "Immune System Management."

-- He still hasn't replaced Dr. Eoghan O'Shea but his websites still say he has at least one "medical doctor" on staff.

-- The CCRG website began proclaiming that it had launched a lawsuit again CTV and W-Five more than 2 years ago but it has never come to court.

-- With the words "swindling people living with cancer is one of most despicable forms of fraud" the Competition Bureau launched "Project False Hope" last March to coincide with Fraud Awareness Month. It comprises 2 clever features meant to steer the unwary away from phony "cancer clinic." The Bureau grumbles that it has the power to do more. Don't hold your breath.

-- The Ottawa Citizen reported the other day that Tony Clement has folded under the intense pressure brought against his Bill C-51 by the Natural Food Products manufacturers. The original bill had enough power to force the CCRGs and ISMs to submit medical claims to scientific rigor. What with Parliament set to adjourn for the summer, it now appears certain Bill C-51 will go to the Standing Committee on Health for review and revision.

Gawd! Maybe we're all wrong: maybe what we've really got here is a candidate for the Nobel Prize for Chemistry. You take a blood and/or urine sample from a cancer sufferer's, send it to the Wizard of Oz out on Woodroffe Avenue to run thru his equipment, then feed the sufferer what the Wizard says is lacking to eradicate his tumor. So simple! How could all those scientists miss it? Must be Big Pharma squashing all the little guys again.

Regards . . .

Quickly checking some of those sites, Project False Hope seems like a nice idea, but as our reader points out, is largely toothless. What it does have is a dummy natural product site and quiz to help identify health fraud, but little else (and no mention of particular companies or groups that should be avoided). I wasn't able to find specific details about the proposed changes to C-51, but it sounds like the revised bill will create a separate category for natural health products (the current version has them grouped with prescription drugs as 'therapeutic products') which takes acknowledges "that natural health products are generally of lower risk and that their long history of use has some value." [Globe and Mail] I'll be interested to see if the proposed changes alter any of C-51's language dealing with standards of evidence and marketing for natural products which I thought was one of the major benefits of the original bill.

Visitor number 10000 [Mailund on the Internet]

Posted: 16 Jun 2008 11:48 AM CDT

I just noticed that I’ve passed 10,000 hits since I restarted my blog! 10,429 right now, to be precise. Cool.

Umbilical cord therapy gives blind girl some sight [Mary Meets Dolly]

Posted: 16 Jun 2008 10:53 AM CDT

From the Arkansas Morning News:

MOUNTAIN HOME - When 9-year-old Kacie Sallee saw her father's face more
clearly for the first time in her life, she had a question.
"She said, 'Is that what he looks like?"' said her mother, Marinda Sallee.

Kacie,
who is blind, returned last week from China, where she received
umbilical-cord stem cell treatment in hopes of improving her eyesight.
The nearly four-week trip and medical treatment was paid through
$60,000 in local donations.

Kacie was born with septo-optic
dysplasia, an underdevelopment of the optic nerve and pituitary gland.
She could see bright colors out of her right eye but only light and
dark out of her left eye.

During treatment overseas, her family
started noticing improvements. Kacie looked at a photograph of her
father, Stephen Sallee, on the computer, and saw his eyes and mouth
were more defined, Marinda Sallee said.
"Before, she would look at a face and say it had spots on it," she said. "It's little things, but for us, it's huge."
Now, Kacie is starting to see bright colors out of her left eye, which
she could never detect before, Sallee said. She also can count fingers
when they are held about four inches away from her face, she said.

Good for Kacie. I thank her and her family for being pioneers. It is a testament to how ignorant and one-minded our media is that a search in Google news for Kacie Sallee yields only 2 results. If I were an American with a disease or disability I would be hopping mad, not at Geaorge Bush and his supposed strangle hold on stem cell research, but the media and the politicians who keep insisting that money is best spent in the embryonic stem cell area.

Your personal health: Trusera launches and thoughts on participatory medicine. [business|bytes|genes|molecules]

Posted: 16 Jun 2008 10:05 AM CDT

Earlier today I got an email announcing the official launch of Trusera, a site that allows people to share their knowledge of diseases and treatments with their peers and others in the community. I remain fascinated about how sites like Trusera and iMedix will complement PHRs like HealthVault and Google Health (and lets not forget personal genetics). Leroy Hood, in his talks about P4 Medicine says that the future of medicine is participatory. We are still in the early days, with limited patient education, services that aren’t quite there yet, a somewhat ambiguous regulatory scenario and no clear idea of who owns what piece of information.

Over the next few years we will get a better picture of how we will become more direct players into our own healthcare and wellness. We will not only have access to resources and services, but the knowledge and a medical system that actively encourages patients to work with them in a collaborative approach to treat illnesses. Let’s see how many years few ends up being.

Technorati Tags: Personal Health, Trusera, P4 Medicine

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Vital Signs [Sciencebase Science Blog]

Posted: 16 Jun 2008 07:00 AM CDT

Homeopathy rVita emailed me today to enthuse about a purportedly “wonderful resource”, which is apparently the web’s first integrative medicine community (funny they should claim that as I had someone else emailing to tell me yesterday about their first such site too).

Anyway, I checked out the site, and am very, very disappointed, the first article I read was wrong, wrong, wrong. Homeopathy is most certainly not a viable alternative to vaccination against lethal diseases like polio, tetanus, and measles. To claim otherwise is not only seriously misleading but incredibly dangerous.

We’ve discussed some of the supposed issues surrounding possible problems with conventional vaccines here before, but homeopathy cannot prevent anyone from contracting such serious illness. No matter how hard followers of Hahnemann’s idea that diluting a substance repeatedly until absolutely none of the original compound remains in one’s vial and all the while repeatedly bashing the vial against a Bible believe it to work, it does not.

There is
no
valid, reproducible
evidence of the
efficacy of
homeopathy as prophylaxis
for serious diseaseThere is no valid, reproducible evidence of the efficacy of homeopathy as prophylaxis for serious disease where a vaccine would usually be used to prevent infection. The rVita article claims:

“Based on principles of natural law, you can receive protection against the flu or any disease including polio, tetanus, and measles by natural immunity.”

Seriously, there is no scientific basis nor evidence for any of the claims of homeopaths, particular with regard to prophylaxis against lethal diseases. This is as true in National Homeopathy Week as at any other time of the year.

rVita originally suggested the site would be “wonderful resource for any upcoming articles you might be planning on alternative or integrative medicine, Health 2.0, health resources on the Internet, or any other health-related topics,” well it does provide fodder for my highlighting some of the sillier claims of alt med. I hope they’ve also emailed my good friend Dr Ben Goldacre of the Bad Medicine site, I’m sure he’ll peruse it in even greater detail and point out the fatal flaws.

Apparently, for users of the rVita community, “whether researching alternative remedies for allergies, infertility, insomnia, chronic pain or even adjunctive care for cancer, users can turn to rVita for help in separating the science from the snake oil.”

Hmmm…as well as the unfounded case of homeopathy, they also discuss Reiki therapy, therapeutic touch, art therapy and the like. Beyond, the placebo effect (which is admittedly very powerful) none of these or many other alternative therapies have any basis in reality

The exceptions, of course, are some herbal remedies. After all, a large proportion of modern drugs from aspirin and AZT to ephedrine and taxol are based on natural products. And some of the manipulating methods such as osteopathy and chiropractic, while dubious in their origins and some of their wider claims, do have physical effects. I was discussing such matters as the claims of chi, energy fields and auras with a colleague in the telecommunications industry who asked, scathingly, “In what units is this universal energy measured?” It’s a rather insightful put down.

Meanwhile, Niteen Bhat Founder CEO of rVeda Inc, of Santa Clara, California, and parent company of the rVita website, contacted me in response to my email respone to their approach. This is what he had to say:

I just wanted to highlight a few things about our philosophy to present our side of the story: Our goal is to bring perspectives from both for “for” and “against” constituents for a particular therapy or modality to enable informed decision making and separate science from snake oil. We welcome experts such as yourself to either comment on any article or even write your own articles that highlight issues with any remedy. That’s the power of Web 2.0 that we are unleashing on CAM.

Having said that, consumers and integrative medicine folks are finding some of these therapy to be effective even though scientific trials are inconclusive or not done yet. One of the reason being that many CAM therapies take personalized medicine approach and essentially have slightly different variants of therapies for each individual. This is exactly the reason we currently do not promote product sales, or do-it-yourself therapies, but expect consumers to get healed via licensed CAM practitioners.

Our content is overseen by conventional medicine MDs (I have copied our Chief Medical Advisor on this email). We did discuss the issues raised and came to [the] conclusion that we need to highlight practitioner articles as such so that we keep sanctity of our select/carefully chosen experts and their opinions. We have decided to separate practitioner articles under separate categories.

So, my review of their site has had a rather positive effect, but efforts to dry up supplies of snake oil must continue.

Many commentators will not accede to using words such as “complementary” or “integrated” to refer to alternative medicine, the name change falls into the same camp as switching from “creationism” to “intelligent design”, as far as I am concerned. Show me the evidence in the form of large-scale, robust, placebo-controlled, double or even triple, blind, clinical trials, however, not spurious poorly controlled tests and selective meta studies, and I’m a believer.

If it produces a sound akin to that of the aquatic avian species falling under the taxonomic name Anas platyrhynchos platyrhynchos, then it really is best avoided, especially if you wish to stay free of lethal diseases.

For an excellent summary of alternative medicine the fact and the fiction, check out Singh and Ernst’s book Trick or Treatment

A post from David Bradley Science Writer

Vital Signs

Streets of Philadelphia [The Gene Sherpa: Personalized Medicine and You]

Posted: 16 Jun 2008 06:00 AM CDT

I want to point all of you to a comment on my blog. This is in regards to my post yesterday. I was accused of responding arrogantly. I don't think it is arrogance....I am just shocked and awed that...

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My Newest Genetics Experiment [Eye on DNA]

Posted: 16 Jun 2008 04:32 AM CDT

Megan
Born last Monday
3.78 kg (8.3 lbs)

Freeing My Father's Scientific Publications [The Tree of Life]

Posted: 16 Jun 2008 02:15 AM CDT

Today is Father's Day. It was a great day for me, hanging out with my kids and wife and doing things around town here in Davis (we kind of made it Father's Weekend and did some activities on Saturday too). Despite the wonderful weekend, this day is also filled with melancholy for me when I think about my father, Howard Eisen, who died when I was a freshman in college. I miss him greatly. But whenever I think about him I think about how he almost certainly would be really proud that his two sons (me and my brother Michael at Berkeley) are now scientists.

You see, my father was a scientist too --- an MD who did research at the NIH, focusing mostly on hormone receptors. Given my propensities for putting things on the web and trying to disseminate scientific information, I cam up with a plan last night to create some sort of web page in his honor with some information about his work and his life.

The thing is, I actually know little about his work, because while I was growing up, my parents never really talked about the details of their work (my mom is a scientist too). Sure, we went to the NIH occasionally and most of my parents friends were scientists. And they talked sciency talk. But they did not really discuss details of their work. I think in the end, this is partly why my brother and I did not shun the family business and went into science.

So, of course, being the obsessed Open Access advocate, the first thing I decided to look at was what publications of my fathers I could get my hands on. This was both to read them and to make them available on this tribute page.

So - my first step in this journey was to search Pubmed for Eisen HJ. And then I had to remove the publications by another Eisen HJ. And so I was left with 35 publications in PubMed (I know he had some other articles as well as chapters in books and such but this is a good start). So then I asked - which of these were available online in one way or another. According to Pubmed 24/35 were available online. Of those available online:

Pubmed Central: 3
Free access: 13
Fee access: 8
Unavailable: 11.

This made me both happy and sad. I was glad to see some of his publications in Pubmed Central (thanks to PNAS and the Biochemistry Journal for putting them there). It was also good to see many available for free, even if this was only at some journals site. So - thanks to journals like J. Biol. Chem. for making the material available online for free. But I was a bit saddened to see how many of his papers, which are now all over 20 years old, being available only for a fee. And I was also a bit saddened to see how many had not yet made it into the digital world.

So - what to do next? Well, my goal is to get access to all his papers and then to free them up to the world. So my first step was to see if any of the ones that Pubmed did not have links for might be available online anyway. And indeed a few were. For example, Pediatric Research back issues are available online. And these are free. In addition, his papers in Biochemistry, J. Steroid Biochemistry and Advances in Genetics is available for a fee but it is not linked from Pubmed. So with this information the new tally was

Pubmed Central: 3
Free access: 14
Fee access: 11
Unavailable: 7

Getting digitized.
So for those 7 that are currently unavailable (at least anywhere I could find) digitally, my next step is to try and lobby the journals to make them available. For some journals, this has some hope (well, not per se my lobbying, but they may make them available). For example, Endocrinology has some back issues available but just not all the way back to some of my father's publications in that journal. So, I wrote to the journal Endocrinology using the link from the journal site and asked what their plans were for older issues. And I will post here if I get a response. I am doing the same for all the other unavailable publications, although some of the journals seem to not exist anymore.

Convincing "free" access journals to deposit old papers in PMC.
My next goal is to see if the "free" access journals have any plans to submit stuff to Pubmed Central. Yes, I know PMC is not perfect, but I believe it is better to have things in PMC than just on a journals website. So I am writing to all these journals to find out if they have any plans to deposit this material.

Freeing up the "fee for access" papers.
My final initial goal, and probably the most challenging, is to figure out ways to make the papers that are current "fee for access" available for free. If these were my papers, I suppose I could put many of the PDFs on my own web site. Perhaps I can do this for my father's publications (does the right to do this get passed down?). Of course, first I have to get the PDFs and it just seems weird to me to have to pay to get access to papers my father wrote. Another possibility is that the journals would let me pay an OA fee to free up these old papers. I am going to look into that although I cannot really afford it. A final possibility would be to get the papers into PMC without the journals explicit agreement. Perhaps because my father was a government employee, the copyright would allow depositing in PMC? I do not know.

So right now, the process is incomplete. I am actually learning a good deal about OA from looking into older papers rather than just all the new papers I tend to focus on. And hopefully in the process I can free up all of my father's papers so that his scientific legacy does not fade away as rapidly due to lack of access. And then next maybe I can focus on my grandfather's publications.

Anyway -- here is a list of my father's publications with links and/or comments on their availability.

Simons SS Jr, Pumphrey JG, Rudikoff S, Eisen HJ. Identification of cysteine 656 as the amino acid of hepatoma tissue culture cell glucocorticoid receptors that is covalently labeled by dexamethasone 21-mesylate. J Biol Chem. 1987 Jul 15;262(20):9676-80. PMID: 3597435.
Cresteil T, Jaiswal AK, Eisen HJ. Transcriptional control of human cytochrome P1-450 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human tissue culture cell lines. Arch Biochem Biophys. 1987 Feb 15;253(1):233-40. PMID: 3813564.
Eisen LP, Reichman ME, Thompson EB, Gametchu B, Harrison RW, Eisen HJ. Monoclonal antibody to the rat glucocorticoid receptor. Relationship between the immunoreactive and DNA-binding domain. J Biol Chem. 1985 Sep 25;260(21):11805-10. PMID: 3840164
Antakly T, Eisen HJ. Immunocytochemical localization of glucocorticoid receptor in target cells. Endocrinology. 1984 Nov;115(5):1984-9. PMID: 6208016
Harmon JM, Eisen HJ, Brower ST, Simons SS Jr, Langley CL, Thompson EB. Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies. Cancer Res. 1984 Oct;44(10):4540-7. PMID: 6331880
Reichman ME, Foster CM, Eisen LP, Eisen HJ, Torain BF, Simons SS Jr. Limited proteolysis of covalently labeled glucocorticoid receptors as a probe of receptor structure. Biochemistry. 1984 Oct 23;23(22):5376-84. PMID: 6391542
Nebert DW, Eisen HJ, Hankinson O. The Ah receptor: binding specificity only for foreign chemicals? Biochem Pharmacol. 1984 Mar 15;33(6):917-24. Review. PMID: 6324804
Nebert DW, Brown DD, Towne DW, Eisen HJ. Association of fertility, fitness and longevity with the murine Ah locus among (C57BL/6N) (C3H/HeN) recombinant inbred lines. Biol Reprod. 1984 Mar;30(2):363-73. PMID: 6704471
Foster CM, Eisen HJ, Bloomfield CD. Covalent labeling of rat thymocyte and human lymphoid glucocorticoid receptor. Cancer Res. 1983 Nov;43(11):5273-7. PMID: 6577947
Karenlampi SO, Eisen HJ, Hankinson O, Nebert DW. Effects of cytochrome P1-450 inducers on the cell-surface receptors for epidermal growth factor, phorbol 12,13-dibutyrate, or insulin of cultured mouse hepatoma cells. J Biol Chem. 1983 Sep 10;258(17):10378-83. PMID: 6309801
Mariani G, Kortright KH, Eisen HJ, Adamson RH, Waldmann TA. A methodological approach for the study of protein synthesis by cell cultures in vitro. J Nucl Med Allied Sci. 1983 Jul-Sep;27(3):237-47. PMID: 6198498
Simons SS Jr, Schleenbaker RE, Eisen HJ. Activation of covalent affinity labeled glucocorticoid receptor-steroid complexes. J Biol Chem. 1983 Feb 25;258(4):2229-38. PMID: 6687388.
Tukey RH, Hannah RR, Negishi M, Nebert DW, Eisen HJ. The Ah locus: correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA. Cell. 1982 Nov;31(1):275-84. PMID: 6186383
Legraverend C, Hannah RR, Eisen HJ, Owens IS, Nebert DW, Hankinson O. Regulatory gene product of the Ah locus. Characterization of receptor mutants among mouse hepatoma clones. J Biol Chem. 1982 Jun 10;257(11):6402-7. PMID: 6896205
Nebert DW, Negishi M, Lang MA, Hjelmeland LM, Eisen HJ. The Ah locus, a multigene family necessary for survival in a chemically adverse environment: comparison with the immune system. Adv Genet. 1982;21:1-52. Review. PMID: 7036691. Available online for fee but not linked from Pubmed.
Eisen HJ, Schleenbaker RE, Simons SS Jr. Affinity labeling of the rat liver glucocorticoid receptor with dexamethasone 21-mesylate. Identification of covalently labeled receptor by immunochemical methods. J Biol Chem. 1981 Dec 25;256(24):12920-5. PMID: 6895516
Hannah RR, Nebert DW, Eisen HJ. Regulatory gene product of the Ah complex. Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene binding to several moieties in mouse liver cytosol. J Biol Chem. 1981 May 10;256(9):4584-90. PMID: 7217100
Stevens J, Eisen HJ, Stevens YW, Haubenstock H, Rosenthal RL, Artishevsky A. Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes. Cancer Res. 1981 Jan;41(1):134-7. PMID: 7448753
Nebert DW, Eisen HJ, Negishi M, Lang MA, Hjelmeland LM, Okey AB. Genetic mechanisms controlling the induction of polysubstrate monooxygenase (P-450) activities. Annu Rev Pharmacol Toxicol. 1981;21:431-62. Review. PMID: 7016012
Markoviƒá RD, Eisen HJ, Parchman LG, Barnett CA, Litwack G. Evidence for a physiological role of corticosteroid binder IB. Biochemistry. 1980 Sep 30;19(20):4556-64. PMID: 7426614. Available online to purchase though no listed in Pubmed.
Eisen HJ. An antiserum to the rat liver glucocorticoid receptor. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3893-7. PMID: 7001446
Hannah R, Simkins R, Eisen HJ. Synthesis of alpha-fetoprotein and albumin by fetal mouse liver cultured in chemically defined medium. Dev Biol. 1980 Jun 15;77(2):244-52. PMID: 6156873
Okey AB, Bondy GP, Mason ME, Kahl GF, Eisen HJ, Guenthner TM, Nebert DW. Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J Biol Chem. 1979 Nov 25;254(22):11636-48. PMID: 500663
Rechler MM, Eisen HJ, Higa OZ, Nissley P, Moses AC, Schilling EE, Fennoy I, Bruni CB, Phillips LS, Baird KL. Characterization of a somatomedin (insulin-like growth factor) synthesized by fetal rat liver organ cultures. J Biol Chem. 1979 Aug 25;254(16):7942-50. PMID: 468799
Simkins RA, Eisen HJ, Sparks JW, Glinsmann WH. Development of glucogenesis from galactose by fetal rat liver explants in organ culture. Dev Biol. 1978 Oct;66(2):353-60. PMID: 700252
Simkins RA, Eisen HJ, Glinsmann WH. Functional integrity of fetal rat liver explants cultured in a chemically defined medium. Dev Biol. 1978 Oct;66(2):344-52. PMID: 81156
Eisen HJ, Glinsmann WH. Maximizing the purification of the activated glucocorticoid receptor by DNA-cellulose chromatography. Biochem J. 1978 Apr 1;171(1):177-83. PMID: 646815
Eisen HJ, Glinsmann W. Partial purification of the glucocorticoid receptor from rat liver: a rapid, two-step procedure using DNA-cellulose. Biochem Biophys Res Commun. 1976 May 17;70(2):367-72. PMID: 180989
Eisen HJ, Ginsberg AL. Letter: Disulfiram hepatotoxicity. Ann Intern Med. 1975 Nov;83(5):673-5. PMID: 1200504. Back issues not currently available.
Eisen HJ, Glinsmann W. Partial purification of glucocorticoid receptor from rat liver using DNA-cellulose. J Steroid Biochem. 1975 Jul;6(7):1171-3. PMID: 170470. AVAILABLE FOR FEE BUT NOT LINKED FROM PUBMED.
Glinsmann WH, Eisen HJ, Lynch A, Chez RA. Glucose regulation by isolated near term fetal monkey liver. Pediatr Res. 1975 Jul;9(7):600-4. PMID: 125868. AVAILABLE FREE EVEN THOUGH MEDLINE DOES NOT HAVE LINK.
Eisen HJ, Goldfine ID, Glinsmann WH. Regulation of hepatic glycogen synthesis during fetal development: roles of hydrocortisone, insulin, and insulin receptors. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3454-7. PMID: 4357871
Eisen HJ, Glinsmann WH, Sherline P. Effect of insulin on glycogen synthesis in fetal rat liver in organ culture. Endocrinology. 1973 Feb;92(2):584-8. PMID: 4682869. Wrote to ask if they will become available.
Hellman DE, Eisen HJ, Goodman HM. The effects of hypophysectomy on phosphorylase activity in adipose tissue and muscle. Horm Metab Res. 1971 Sep;3(5):331-5. PMID: 4332655
Eisen HJ, Goodman HM. Growth hormone and phosphorylase activity in adipose tissue. Endocrinology. 1969 Feb;84(2):414-6. PMID: 4303531. Wrote to ask if they will become available.

On review quality… [Mailund on the Internet]

Posted: 16 Jun 2008 12:31 AM CDT

Following up on the last post, and an older one, I’m going to rant a little bit about the reviews I’ve gotten on two papers recently.

I’m not complaining about the reviews I’ve gotten for the Bioinformatics paper I mentioned in the previous post. Those are detailed, thoughtful, relevant and all reasonable. There my only problem is that I have a page limit that keeps me from adressing all the comments.

What I am a bit miffed about is two papers submitted to BMC Bioinformatics. Do not take it as a critisism of that journal, though, I have also gotten nice reviews there. I have another paper submitted there, that is getting nice reviews (in the sense that there are lots of suggestions to consider, not that they are just positive). Not so for the last two papers.

First of all, the review reports are very short. Maybe 15-20 sentences. Secondly, there aren’t really any constructive criticism. Not surprising with less than 20 sentences, of course. Thirdly, and this is the most annoying, they haven’t made any decision!

The “positive” reviews are just summaries of the paper (essentially paraphrasing the abstract). The “negative” reviews are saying things like: “I do not really like this / I do not find it interesting” or “other people are doing something similar”.

Of course reviewers are permitted to not like a paper and to not find it interesting. They shouldn’t make their decision on this, but on whether the results are novel and sound. If they think that the results are too small an increment on existing work — and there will always be similar work out there, if I submit it to BMC; it it was truly novel I would go for higher impact — in that case they should say so, justify it, and reject the paper!

Telling me that they do not find the results interesting, and then telling me to resubmit is just crazy! How can I make any improvements if that is all the criticism I get?

If I resubmit, the paper will end up with the same reviewers, and they still won’t like it.

The form letter from the editor just asks us to resubmit and include a cover letter “addressing the reviewer concerns”. That is of no help at all! “To make the paper more interesting, we have included a Dilbert strip and a picture of a clown.” Is that going to work? I doubt it.

This is really pissing me off.

If, as a reviewer, you do not have any constructive criticism — good or bad — just make your decision and let us get on with our lives. If the paper is rejected, it would probably also be rejected after a resubmission, but now I know that so I can decide on whether to abandon the paper or try somewhere else.

It is not just the reviewers that are the problem here, though. In a situation like this, I think the editor has a lot of the responsibility. The final decision is his, so he should get involved at some point. By now, he should a good idea about whether the papers will get accepted or rejected. After all, there are no additional experiments or improvements suggested, so the content of the papers are not going to change.

As a side note, BMC isn’t that bad in this regard. We once had a paper at European J of Hum Gen in review for more than a year, where each iteration consisted of very minor changes but the form letter kept telling us that no decision was made yet.

We all want our papers as good as we can get them, so if you have made your decision then let us know! If it gets rejected, we wont waste any more time on it, and if it gets accepted we will still address reasonable comments to improve the final version.

You are no more “unable to make a decision” at this point than you will be after a resubmission, if the reviews do not ask for any actual additional work!

Grrr!

Thinking About Grad School [Bitesize Bio]

Posted: 16 Jun 2008 12:01 AM CDT

Here’s a video that might help prospective grad students out there. I came across it just doing a random search, but it’s a 7 and a half minute clip with grad students, faculty and staff of Duke University giving advice for you on your search

Connection between Video Games and Bioinformatics? [The Tree of Life]

Posted: 15 Jun 2008 07:30 PM CDT

The Scientist Magazine has a nice piece on one of my favorite people in all of Science - Sean Eddy. In the article, they discuss how Sean is one of those bioinformatics folks who does not just hack together some code to do something but actually writes really good code for his programs. For those of you who do not know, Sean has made a whole collection of software tools for biologists (see his web site here). Perhaps the most widely used is HMMER, which is designed for making and using hidden markov models. But there are some other good ones he has put out. My favorite is Forester, which was made by Christian Zmasek in his lab and is supposed to be available here, although the site is not working right now. I like this because, well, it is software for "phylogenomic" analysis.

Anyway - it is a nice article about Sean, especially the parts talking about how his background in video games contributed to his success in bioinformatics. Back to something I said above, Sean is without a doubt one of my favorite people in science. There are many reasons for this but here are a few.

He is very open with ideas.

Once, at a conference, I gave a talk on this bizarre new pattern we had found when we were comparing the genomes of E. coli and V. cholerae. We had found that when we did genome-level alignments of these species there was an X-like pattern (see our paper on this here). Anyway, in the talk I said something to the effect of "we have no friggin idea how these X-like alignments could be generated" And Sean, I think in the quesiton session, pointed out that in another paper of ours we had seen what appeared to be symmetric inversions occurring around the origin of replication and that could create the X-alignment. And lo and behold he was right. We got the paper, but in a large part it was his push that got us looking at the inversions sooner than we would have.
He is very open with science.

Most of Sean's work is on the open side of science. Open Source software. Open Access publications. Open everything. And I should point out that it was a talk by Sean that catalyzed my conversion into an Open Science supporter. I was attending a meeting in Ft. Lauderdale to discuss data release policies for genome projects. This meeting led to the "Ft Lauderdale Agreement" on data release, by the way. A the meeting there were many genomics players like Eric Lander and Francis Collins who were trying to push for not completely open data release policies where genome centers could release data but there would be constraints placed on the use of the data so that the genome centers would be the first to be able to publish genome scale analysis of an organisms genome sequence.

At the time I was working at TIGR and I supported this notion of basically letting people search for a few genes of interest but preventing them from doing genome analyses. And then Sean got up and gave a talk and, well, blew my mind. I am sure I have notes somewhere from the meeting but basically what he said was - the genome projects whole point is to generate genome data for people to do genome-level analysis. So how on earth can we justify preventing exactly the type of analysis that the projects were designed to generate. He was not saying that we should not somehow protect the genome centers. What he was saying was that for the benefit of science, we need to find a way to allow people to do genome-level analyses immediately on the data. And he also said that the risks of releasing ones data with no restrictions are much less than everyone claims. I think he convinced many people that genome centers needed to open up their data release policies a bit more. And he convinced me.

And so I went home from that meeting and decided to release the data from as many of my genome projects as I could, with NO restrictions (e.g., this is what we did with Tetrahymena). And also, this new found belief in openness helped pave the way for my conversion to being an Open Access publishing supporter.

Anyway, glad to see Sean getting positive press. It is well deserved. Now off to play some video games.