Thursday, September 25, 2008

The DNA Network

The DNA Network

Why would a mutation in Google-cofounder, Sergey Brin, cause Parkinson's disease? [Discovering Biology in a Digital World]

Posted: 25 Sep 2008 07:39 PM CDT

Lots of bloggers in the DNA network have been busy these past few days writing about Google's co-founder Sergey Brin, his blog, his wife's company (23andme), and his mutation in the LRRK2 gene.

ResearchBlogging.orgI was a little surprised to see that while other bloggers (here, here, here, and here) have been arguing about whether or not the mutation really increases the risk to the degree (20-80%) mentioned by Brin, no one has really looked into the structure and biochemistry of the LRRK2 protein to see if there's a biochemical explanation for Parkinson's risk. I guess that task is up to me.

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Protective factor against breast cancer in Black women? [Yann Klimentidis' Weblog]

Posted: 25 Sep 2008 06:48 PM CDT

Breast cancer incidence has been found to be higher in those with higher SES, and incidence is highest among Whites, followed by Blacks, then Asians and Hispanics. Using several previous studies, this study finds that the disparity in breast cancer risk between ethnic groups can be accounted for by differences in SES, except for the disparity between Blacks and others.
"In contrast, for the black population, seven of the eight
analyzed datasets showed no difference in the incidence
of breast cancer at highest level of SES compared to the
lowest level, with only one dataset demonstrating a statistically significant disparity (data set 1: IRR 1.39, lower limit of 95% CI=1.04). This suggests that, as opposed to the apparent contributory effect of high SES on breast cancer risk in white, Hispanic and Asian/Pacific-Islander women, the risk of breast cancer in black women may not be significantly modified by SES."
in the conclusion:
"As for black women, the overall lack of statistically significant incidence rate ratios in Table 1 suggests that SES effects do not play an important role in modifying the risk of breast cancer in this population. This suggestion is supported by Chlebowski's analysis, in which adjustment for SES-correlated breast cancer risk factors failed to eliminate the differencein hazard ratio of between black women and women of other races. Taken together, these findings imply the presence of a protective factor, which is not modified by SES, against breast cancer in black women."
There's a brief mention at the end about the grade and aggressiveness of breast cancer among Black women.

Disparities in breast cancer incidence across racial/ethnic strata and socioeconomic status: a systematic review
Vainshtein J.
J Natl Med Assoc. 2008 Jul;100(7):833-9.
OBJECTIVES: A higher incidence of breast cancer has been reported both in white women and women of higher socioeconomic status (SES) compared to women of other races and lower SES, respectively. We explored whether differences in SES can account for disparities in breast cancer incidence between races. METHODS: We identified several studies published between 1990 and 2007 that addressed disparities in breast cancer incidence across racial and socioeconomic strata. For each study, we calculated incidence rate ratios (IRRs) for breast cancer incidence in the highest strata to lowest strata of SES for white, black, Hispanic and Asian/Pacific-Islander populations. We then used these IRRs to compare trends in SES and breast cancer incidence between races and across studies. RESULTS: The studies we identified revealed that the magnitude of the disparity in breast cancer incidence between races decreases with increasing SES. While individual census-tract based studies' methods of assessing the association between SES and breast cancer incidence did not identify consistent trends between races, adjustment for risk factors closely correlated with SES eliminated the statistical differences in breast cancer incidence between women of white, Hispanic and Asian/Pacific-Islander, but not black, ethnicity. CONCLUSION: We found that racial differences in breast cancer incidence can largely be accounted for by ethnic differences in SES among white, Hispanic and Asian/Pacific-Islander women, but not between these populations and black women. We further highlight important differences in methodology between previously published studies that may account for their disparate findings.

Obama & McCain in Nature [The Daily Transcript]

Posted: 25 Sep 2008 06:03 PM CDT

Umm ...

ObamaMccainNature.jpg

Seriously, the latest issue of Nature has a special section on the US presidential election, including another Q&A with the candidates:

Barack Obama accepted Nature's invitation to answer 18 science-related questions in writing; John McCain's campaign declined. Obama's answers to many of the questions are printed here; answers to additional questions (on topics including biosecurity, the nuclear weapons laboratories and US participation in international projects) can be found at www.nature.com/uselection. Wherever possible, Nature has noted what McCain has said at other times on these topics.

Link to the Nature article.
Link to Nature's election coverage.
Link to ScienceDebate's Top 14 Questions.

(photo courtesy of Ed from Not Exactly Rocket Science)

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Feynman videos [Mailund on the Internet]

Posted: 25 Sep 2008 04:16 PM CDT

Feynman has always been a hero to me…

The Prince and the P [Genome Blog]

Posted: 25 Sep 2008 03:45 PM CDT


Maybe Prince Charles should look again at Malthus. Malthus looked a population (P). Was Malthus wrong? In the early 1800’s, Malthus worried that the human population would soon outstrip the ability of humans to feed themselves. By the mid 1940’s agricultural methods were not keeping up with the human population and widespread famine seemed possible. Then, improved agricultural methods increased food production. Each time as the human population increases, scientific research translated into modern agricultural methods move the line. Which line am I talking about?

Closing Arguments on Big Tobacco, Boston Legal Style [Highlight HEALTH]

Posted: 25 Sep 2008 03:11 PM CDT

The ABC television drama Boston Legal is one of my favorite programs. The show features quick, intelligent dialogue and great performances. Producer David E. Kelly has used Boston Legal as a platform to speak out on a number of issues over the last four seasons. Each installment walks a fine line between entertainment and political/social issues such as the Iraq War, global warming and Hurricane Katrina. Tuesday night’s season premier titled “Smoke Signals” was no exception. In this episode, Kelly tackles big tobacco.

Attorney Alan Shore represents a client who is suing a large tobacco company; her father smoked cigarettes for over 50 years and died of lung cancer. Testifying before the jury, the tobacco company CEO maintained that “we also some good along the way”, asking, “how many industries actually spend money to discourage people from buying their products?” He claimed that “spending billions of dollars on anti-smoking campaigns and youth prevention efforts” is an “unprecedented display of corporate conscience.” In their closing arguments, the defense maintained that there wasn’t conclusive evidence that the tobacco company caused the death of the plaintiff.

Shore delivered powerful closing arguments in the case as only the incomparable James Spader could present. Throughout his closing, he cited research findings and statistics that seemed “made for TV” but are, in fact, very real. In quintessential Highlight HEALTH fashion, I have referenced the studies throughout his closing arguments below. There will only be 12 episodes in this, the fifth and final season of Boston Legal. Enjoy it while you can.

Closing arguments

Michael Rhodes smoked cigarettes for 50 years, got lung cancer and died; we all know what happened here. We also all know this death. Everybody in this room knows somebody who has fought this same battle and dies … agonizing, brutal, excruciating …

But … emotion has no play here. Michael Rhodes was eleven years old when he started smoking, it was 1948. At that time, there was no known risk, and even if there were, at eleven he certainly lacked the capacity to assume it. And after that, he was addicted. They manufacture them to be addictive.

In just the last few years, they’ve increased the amount of nicotine in the average cigarette by 11.6% to make them even more addictive [1]. Recently, we learned that tobacco companies have been adding an ammonia-based compound to cigarettes for years to increase absorption of nicotine [2]. It’s basically the same principle used in crack cocaine.

And let’s look at the obscene strategy they’ve employed here. Smoking may cause cancer, but it didn’t cause this particular cancer. It wasn’t our cigarettes, or it was genetic, or asbestos or a paper mill. Never do they take responsibility ever. And God forbid, if you sue them, they’ll bury you and your lawyer. They might even depose your doctor to death, for good measure. All their insidious methods and cunning corporate tactics aren’t just history, it’s what they continue to do now, today. Because the tobacco industry is like a nest of cockroaches, they will always find a way to survive.

They still go after kids with one strategy after another. They put up brightly colored ads at kid’s eye level in convenience stores. They hire gorgeous twenty-somethings to frequent popular venues and seduce young adults into attending lavish corporate-sponsored parties. Cockroaches will always find a way.

They can’t advertise on TV but they’ve hired PR agencies to hook them up with the film industry. And it’s worked. Researchers estimate that smoking in movies delivers nearly 400,000 adolescent smokers every year [3]. Every time you try to kill the cockroach, it finds another way. It has to, because when you make a product that kills off your consumers, you have to find a way to recruit new customers.

They’ve now got a new feminized version of the macho Camel brand using slogans like “lite” and “luscious” with hot pink packaging. Virginia Slims advertised their “thin cigarette”. Allure Magazine did a whole spread on the cigarette diet [4]. They use social and psychological profiling [5], targeting potential smokers by gender, ethnicity, sexual preference, socioeconomic groups … cockroaches don’t discriminate.

Their CEO comes into this courtroom gloating over their anti-smoking campaign, which is designed to get kids to smoke. In 2003, they spent more than 15 billion on advertising and promotion [6]. That’s a 225% increase from 1998, and they have the audacity to declare they’re trying to discourage smoking. This is not how corporations with a conscience behave.

How in God’s name are cigarettes even legal, can anybody tell me that? They are a deadly concoction of carcinogens that damage every single organ in your body. Why do we not ban them? Because it’s a free country, because freedom of choice is an American ideal worth somebody dying every six seconds? How can any company, especially one with such a conscience no less, knowingly manufacture a product that poisons its users? … and make that product look cool and hip and sexy and fun, so they can get children. How can any attorney defend a company that would do such a thing and how could any society tolerate it, but we do.

There is no conscience at big tobacco. There is no conscience in Washington, which has been bought and paid for by this industry. Conscience has to come from you, the jury. If real regulation is to happen, it has to come from you. People are smoking day after day after day and dying and dying and dying and the tobacco companies keep getting richer and richer. Last year alone, they made 12 billion dollars in profits [7]. How can that be?

How can that be?

References

  1. Connolly et al. Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997-2005. Tob Control. 2007 Oct;16(5):e5.
    View abstract
  2. How an Unregulated Industry Experiments on America’s Kids and Consumers. American Cancer Society Cancer Action Network, American Heart Association, American Lung Association and Campaign for Tobacco-Free Kids. 2008 Feb 20.
  3. Sargent, J. AAP Handout, October 2006. News release, American Academy of Pediatrics.
  4. Morris, L. “The Cigarette Diet.” Allure Magazine. 2000 Mar.
  5. Ling and Glantz. Using tobacco-industry marketing research to design more effective tobacco-control campaigns. JAMA. 2002 Jun 12;287(22):2983-9.
    View abstract
  6. Federal Trade Commission Cigarette Report For 2004 and 2005. United States Federal Trade Commission. 2007
  7. Fortune Global 500 2007: Altria Group.
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This article was published on Highlight HEALTH.

Other Articles You May Like

National Academy Tells Candidates to Start Picking Science Advisers Pronto [adaptivecomplexity's column]

Posted: 25 Sep 2008 03:03 PM CDT

Climate change, stem cells, drug research and regulation, nuclear proliferation, biological terrorism agents, alternative energy technology, nanotechnology, personalized genetics, new computing technologies, nuclear waste storage, perchlorate in our drinking water, space exploration .... all reasons why the next US President needs competent people in key science and technology positions.

Read More...

A change in NIH leadership [The Daily Transcript]

Posted: 25 Sep 2008 02:59 PM CDT

Elias A. Zerhouni, is stepping down as head of the National Institutes of Health.

I heard about the announcement last night at the NERD meeting. Many were happy. Many blog commentators have added their two cents. Here are mine:

1) He's stepping down real soon (the end of October). Why so quickly? Did something happen? And why is this happening just before the elections and not closer to January when the next administration takes over?

2) Zerhouni is an MD, and under his direction there has been more of an emphasis on translational-research and less on basic research. (Read all about it at the NIH Roadmap).You can imagine that most basic researchers have felt neglected. Thus the big question is Will the next NIH director be an MD or a PhD? Or perhaps as a compromise, we could get the someone like Joe Goldstein or Mike Brown from UT Southwestern. These two MDs have been collaborating forever on basic research involving cholesterol metabolism. Their work has not only contributed to our basic knowledge of how cells work but has led to many new treatments (i.e. statins). PhDs want someone up there who appreciate that transitional research NEEDS basic research.

Links around the blogs:
DrugMonkey: Zerhouni to retire, let's all dance the Director Shuffle
Nick Anthis: NIH Director Elias Zerhouni Announces Resignation
Revere: Director of NIH resigns
Bora: Zerhouni to step down

Read the comments on this post...

Reminder: come party with Seattle ScienceBloggers on Saturday at Ozzie's [Discovering Biology in a Digital World]

Posted: 25 Sep 2008 01:00 PM CDT

Dave, Maria, Grrl, and I will all be at Ozzie's in Lower Queen Anne on Saturday afternoon.

I've never met the other three bloggers but after checking out Maria's wedding pictures and the liquid nitrogen, I'm really looking forward to this. We'll be upstairs in the mezzanine and we'll have a ScienceBlogs poster.

Relevant details:

Saturday, Sept. 27th at 4 pm in the upstairs mezzanine at Ozzie's.
Address: 105 W. Mercer St., Seattle, WA 98119

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A Genetic Counselor Responds to “Trig’s Breakthrough” [DNA Direct Talk]

Posted: 25 Sep 2008 12:56 PM CDT

A recent editorial in the Washington Post, “Trig’s Breakthrough,” has caused a lot of discussion in the genetic counseling community. It uses Sarah Palin’s youngest child’s entry on the political stage as a platform to address genetic testing. Roxanne Ruzicka, a genetic counselor in Los Angeles and consultant to DNA Direct, sent a thoughtful commentary [...]

Applied Programming: Course plan [Mailund on the Internet]

Posted: 25 Sep 2008 12:11 PM CDT

Søren and I spent this afternoon planning our upcoming course, Applied Programming (essentially a Python programming class with focus on bioinformatics applications).  See my previous thoughts on the class here and here.

Course plan

The class runs for seven weeks, and this is the plan we came up with is listed below.  There is eight weeks there, since the first and last week are really half-weeks.

Week 1: Introduction to Python

One lecture:

  • Logging into the department’s computers and running Python there (plus how to use Idle).
  • Installing Python on your own computer.
  • Interactive Python sessions
    • expressions
    • comparisons
    • assignments
    • multiple-assignments
  • Using help() to learn more
  • built-in data types
  • scripts in files (and how to execute them)

Week 2: Control structures

First lecture:

  • branching
  • looping
  • indentation

Second lecture:

  • functions
  • (list comprehension)
  • generators
  • exceptions

Hand-in exercise:

  • Locate ORFs in a string
  • Translate them into proteins
  • Calculate frequencies of AA

Week 3: Parsing

First lecture:

  • files and IO
  • string operations

Second lecture:

  • regular expressions

Hand-in exercise:

  • parse table of genes (GFF)
  • parse sequences from FASTA
  • calculate AA frequencies

Week 4: Structuring code

First lecture:

  • modules
  • classes

Second lecture:

  • "Design by Contract"
  • Unit testing

Hand-in exercise:

  • write a class containing a multiple sequence alignment
  • add a method for iterating through the columns of the alignment
  • add a method to restrict to subset of species
  • add a method to slice the alignment
  • add a method to remove all-gaps columns

Week 5: BioPython

First lecture:

  • Introduction to BioPython (and Bio*)

Second lecture:

  • Sequences and sequence parsers
  • NCBI access
  • Blast

Hand-in exercise:

  • Read a list of human genes (or IDs) from a table
  • Download them from NCBI
  • Blast them against the mouse

Week 6: SciPy

First lecture:

  • Plotting using matplotlib (pylab)

Second lecture:

  • Fitting functions
  • Linear regression

Week 7: Go faster stripes (profiling and optimizing)

First lecture:

  • cProfile
  • Timing code-chunks

Second lecture:

  • Algorithmic complexity
  • "Big O" notation (and roughly how to figure it out)

Hand-in exercise:

  • Implement a program that builds a string by appending vs. using join()
  • Measure the running time on both solutions
  • plot and fit to O(n) and O(n2)

Week 8: Introducing the exam project

We still haven’t decided on the exam project, but it is a take-home exam where they will need to write a small program and then hand it in together with a short report.

Teaching material

We had a discussion about the teaching material.  We would really like to have a text book for this, but we have been looking for a while without finding one that fits our needs.

We also thought about using one of the many online introductions.  There are some pretty good ones.

Still, they are typically more or less at the tutorial level, and that we could just as easily write ourselves, and then get it exactly the way we want it.

I wrote my own lecture notes in previous classes (see e.g. here).  It is a lot of work, but it is nice to taylor it exactly to the needs of the class.

The downside is, of course, that the first time the class runs the notes will be pretty short and not proofread in sufficient detail.

The Pre-natally and Post-natally Diagnosed Conditions Awareness Act Passes [Mary Meets Dolly]

Posted: 25 Sep 2008 10:19 AM CDT


A mouthful, but certainly a step in the right direction. From LifeNews:

On Tuesday, the Senate passed a bill via unanimous consent that is designed to help reduce the number of abortions of babies with Down syndrome and other conditions....

The legislation would require giving families who receive a diagnosis of Down syndrome or any other condition, pre-natally or up until a year after birth, pertinent helpful information.

The information would include facts about the condition and connections to support services and networks that could offer assistance in raising a disabled child.

Sen Sam Brownback, a pro-life Kansas Republican and co-sponsor of the bill, told LifeNews.com he's glad the Senate approved it.

"This bill will greatly benefit expecting parents who receive the sometimes overwhelming news that their unborn child may be born with a disability," he said. "This legislation will provide parents with current and reliable information about the many options available for caring for children with disabilities."

He said he hopes it will reduce the percentage of abortions in such cases -- with some studies showing as many as 90 percent of parents with an unborn baby diagnosed as having Down syndrome having an abortion.

That percentage is similar for children pre-natally diagnosed with other conditions such as spina bifida, cystic fibrosis and dwarfism....

The Pre-natally and Post-natally Diagnosed Conditions Awareness Act would provide for the expansion and further development of a national clearinghouse on information for parents of children with disabilities, so that the clearinghouse would be better equipped to assist parents whose children have recently been pre- or post-natally diagnosed.

The bill also provides for the expansion and further development of national and local peer-support programs. The bill also calls for the creation of a national registry of families willing to adopt children with pre- or post-natally diagnosed conditions....

"It is difficult, sometimes overwhelming, for expecting parents to receive news that their unborn child may be born with a disability," Brownback said.

"This legislation will help parents receiving such news by supplying them with current and reliable information about the many options available for caring for children with disabilities," he added.

A general method and good student project for finding interesting anomalies in GenBank [Discovering Biology in a Digital World]

Posted: 25 Sep 2008 08:21 AM CDT

Do mosquitoes get the mumps? Part V. A general method for finding interesting things in GenBank

This is the last in a five part series on an unexpected discovery of a paramyxovirus in mosquitoes and a general method for finding other interesting things.

In this last part, I discuss a general method for finding novel things in GenBank and how this kind of project could be a good sort of discovery, inquiry-based project for biology, microbiology, or bioinformatics students.

I. The back story from the genome record
II. What do the mumps proteins do? And how do we find out?
III. Serendipity strikes when we Blink.
IV. Assembling the details of the case for a mosquito paramyxovirus
V. A general method for finding interesting things in GenBank

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

Figures and Word [Mailund on the Internet]

Posted: 25 Sep 2008 04:26 AM CDT

I’m used to writing my papers in (La)TeX.  In mathematics and computer science, that is the tradition, and quite frankly it is the only choice if you include a lot of math in your documents.

Recently, though, I’m working with people used to writing in Word, and rather than forcing them to learn LaTeX I’ve decided to use Word as well.  Only when the math content is low, though.  Writing math in Word is too painful to even contemplate.

Anyway, for simple text editing I have no complains with Word.  It does what it is supposed to, and I find the grammar checker a great help (I do have a grammar checker in the editor I use for LaTeX, but it isn’t quite as good).

I run into problems when I try to do anything but simple text editing.

Like today, I am trying to insert a figure in a document.  I have a plot in PDF and I want to insert that together with a caption.

I can insert the figure and write the caption in a text box.  No problem.  It looks something like this:

Now, to make the editing easier, I want to group the figure with the caption, so I can move them around as a unit if I need to move them later on.

If I do that, it looks like this:

WTF? Why did it suddenly turn my (vector graphic) PDF into (a very pixilated) bitmap image?

This is so not what I expected, and certainly not what I wanted…

Computing Everywhere [business|bytes|genes|molecules]

Posted: 24 Sep 2008 11:51 PM CDT

Tim O’Reilly’s keynote at Web 2.0 Expo touched upon this. I have written about this before as well, and Nova Spivack adds his voice to a trend that you can call uqbiquitous computing, ambient computing and many other words. I just call it computing everywhere.

It’s easy to make all this sound very scifi. It’s easy to bring up fears of Skynet. What I like to think about is the potential for such efforts to have an impact in so many different areas. In a recent episode of Cranky Geeks, Whitfield Diffie, VP at Sun and a guru in the Crypto world talked about Street View and about people adding their own images, which would allow us to revisit a region after a period of years, to build the kind of composite images that something like photosynth enables. The challenge will be how we make all these streams of data available, how we leverage them, and how we protect them. No trivial task, but one we can address. We must. I missed most of Clay Shirky’s talk at Web 2.0 Expo, but the point he made right in the beginning was that we don’t suffer from information overload, but rather a “filter failure”. In other words, the problem is not from the volume of information available, but the inability of the filters we have used over the years to keep up with the information explosion. Now image this information coming to us everywhere. Now imagine how critical good filters will be. The challenge of the petascale era, whether in science or the general information age is going to be how we harness these information streams, and how we keep them suitably democratic. Should be very interesting to watch all this happen

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Varmus on "The Cure" for Cancer [Bayblab]

Posted: 24 Sep 2008 09:50 PM CDT

"These are incredibly complicated scenes that we're only beginning to understand thanks to the genome project and spinoffs from the genome project.

"And the hope that advocacy groups understandably have – that if we just do a little bit more research and apply it at the bedside, that we're going to cure cancer – is really terribly simplistic.

"And when scientists give support to that simplistic notion, which they are likely to do because it's the way of raising money, they create an expectation that's very hard to meet."

...And he argued that the culture of unrealistic expectations is encouraged by the way science is taught in schools, with a focus on outcomes rather than process.

(More at the Globe and Mail)

My question: what proportion of research funding currently goes to BASIC cancer biology research with no obvious "therapeutic/therapeutic target" pay-off?

Your Doctor and the Drug Companies: A Step Forward on Transparency [adaptivecomplexity's column]

Posted: 24 Sep 2008 09:13 PM CDT

Eli Lilly and Merck are going to start reporting payments made to physicians.

How would you feel if you found out that your physician, who just prescribed you (or your child)that expensive new drug, has been receiving payments from the drug's manufacturer? Or that your physician has just attended a lavish "educational" conference at Lake Tahoe, sponsored by the drug's maker, and devoted largely to pushing the benefits of the drug?

Read More...

Overselling Genomics, Sherpa Plan part 1 [The Gene Sherpa: Personalized Medicine and You]

Posted: 24 Sep 2008 11:13 AM CDT

Yes finally, at last I am going to release my Sherpa Plan! Thank you to all who have helped form this unique set of operating instructions to help rescue the promise of personalized medicine. Now...

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