Thursday, May 8, 2008

The DNA Network

The DNA Network

An attempt to reason out loud [The Daily Transcript]

Posted: 08 May 2008 09:28 PM CDT

The lack of posts has been epic. Sorry life has been just too hectic.

I'll give you a flavor:

Running around. Setting up experiments. Training young rotation students. Off to Microbiology seminar. Off to Cell Biology talk. Off to Montreal. Where next? Vacation? Need to lengthen those telomeres. Paris, Munich, Reykjavik.

Convoluta Roscoffensis.

Need to get data club speaker. Must find new microscope room. Need to get reagent. Try to find protocol. Must get results!

Time to take a break. Flip journal. APC and mRNA? Strange. Too many people study that protein. It does everything and nothing. It's one of these proteins that entices ... study me I'm mutated in 50% of colon cancers ... but do we understand what it does? I'm not so sure. Maybe it's a sick joke. And mRNA? It's everywhere. It's nowhere. It must be somewhere. BUT WHY? We have no clue. Need a new idea.

Back to the lab. Must get results. No time to write. No time to think. Wake up, eat food, walk to the lab. Pipette liquids up and down. Coffee. Passage cells. Snap pictures. Lunch. Pipette more liquids. Type emails. Call thesis advisor. Call long lost friends. Call doctor. Pipette more liquids.

Need a break. Go to pub. Talk about Systems biology one night. All those posers. They don't know what systems is. All this data, what is it good for? Are we all just number collecting machines? N=200,000 and rising. The result, chaos. No insight. A waste of time. Next night, talk about literature. That Gore Vidal. He's incredible. And did you hear about the giant hotel. But then the same question comes up. How's the blog? Not sure. I neglect it. Bye bye readers. My blog must be dead. Have so many ideas. Big ideas. Big science. Little science. Should I continue with it? Euthanasia? Slow quiet death? Apoptois? Autophagy? Entosis. Back to the lab. And It's 9PM. Pipette more liquids. Split cells. Pipette more liquids. Done (well until tomorrow). Walk back home. Eat food. Try to read. Try to watch Jon Stewart. Forget about elections. Drift to sleep.

My blog. What to do. Maybe I need a change. Maybe audio is the next step. Maybe talk about the little bits of science that I love. How to think about a problem. How we figured out the nature of genetic material. The wonder of subcellular automata. How to think. What is an idea. How we are trapped by our own convenient theories. The tragedy of human mind. We are all trapped by misconstrued ideas. But you meet it head on in a personal way as a scientist. YOU REALY DO. So maybe audio is the way to go. Once a week. So much incredible stuff to talk about, so many great stories. So little available on the net. So much crap on blogs. No wonder the average person is confused and afraid of science. But science can be wonderful. Pondering ideas and how to think about life is so liberating. It gives you a precious and fragile possession, self-knowledge.

I'll have to think about it ...

Now where to. Toronto? Really? Let's try.

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Would your class like to clone and sequence plant genes? [Discovering Biology in a Digital World]

Posted: 08 May 2008 07:36 PM CDT

Dave Robinson and Joann Lau from Bellarmine College in Kentucky are going to be describing their student project in a free webinar next Friday, May 16th. Their students clone GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase) genes from new plants, assemble the DNA sequences, and submit them to the NCBI. Here's an example.

Plus, since GAPDH is a highly conserved, it's a great model for looking at evolution.

You can get more information and register here.


The cool thing about plants is that there's lots of material to work with.

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Scientists identify key roadblock to gene expression [Think Gene]

Posted: 08 May 2008 05:41 PM CDT

A team of scientists has provided, for the first time, a detailed map of how the building blocks of chromosomes, the cellular structures that contain genes, are organized in the fruit fly Drosophila melanogaster. The work identifies a critical stop sign for transcription, the first step in gene expression, and has implications for understanding how the AIDS virus regulates its genes. The findings will be published in the 15 May 2008 issue of the journal Nature.

The scientists found that nucleosomes–chromosomal building blocks made up of proteins around which DNA is coiled–occur at precise locations along genes that are actively undergoing transcription. They also showed that RNA polymerase–the enzyme that reads genes as the first step in making proteins–is stopped at the first nucleosome, where it remains idle until it is directed to continue moving forward. “This discovery is important because nucleosomes are barriers to transcription and we now are seeing the impact of nucleosome organization on RNA polymerase,” said lead investigator B. Franklin Pugh, professor and Willaman Chair in Molecular Biology at Penn State University.

Using state-of-the-art ChIP-sequencing, a genome-mapping tool provided by collaborator Stephen S. Schuster, Penn State professor of biochemistry and molecular biology, and computational predictions developed by collaborators Ilya Ioshikhes, an assistant professor at Ohio State University, and Istvan Albert, a research assistant professor of bioinformatics at Penn State, the scientists precisely mapped the locations of hundreds of thousands of nucleosomes. The scientists then compared these maps to the team’s earlier maps of the baker’s yeast Saccharomyces cerevisiae, revealing that evolution has organized nucleosomes differently in simple life forms compared to more complex organisms like the fruit fly.

In yeast, a nucleosome sits on top of the transcription start site, so RNA polymerase must contend with that nucleosome as soon as it begins to transcribe the gene. In contrast, nucleosomes are positioned further downstream in fruit flies, so transcription starts but then soon pauses at the first nucleosome the RNA polymerase encounters. “This pause is maintained until chemical signals from the cell cue the removal of the nucleosome and encourage the RNA polymerase to continue along its path,” said key collaborator David S. Gilmour, professor of molecular and cellular biology at Penn State and an expert on the pausing of RNA polymerase.

“A year ago, we could name about 10 genes that work this way. Now, we know of 1,000 in flies alone and we suspect there could be many more in humans,” said Gilmour. “Even HIV genes have a paused RNA polymerase. Release of this pause may be key to activating HIV replication of otherwise latent viruses. Taking advantage of this new understanding might enable the development of more effective anti-viral drugs,” he said.

“The bottom line is that we need to know how the expression of genes is regulated in order to understand the underpinnings of most human diseases, and these findings take us one step closer,” said Pugh.

Source: Penn State

New cancer gene found [Think Gene]

Posted: 08 May 2008 05:39 PM CDT

Researchers at the OU Cancer Institute have identified a new gene that causes cancer. The ground-breaking research appears in Nature's cancer journal Oncogene.

The gene and its protein, both called RBM3, are vital for cell division in normal cells. In cancers, low oxygen levels in the tumors cause the amount of this protein to go up dramatically. This causes cancer cells to divide uncontrollably, leading to increased tumor formation.

Researchers used new powerful technology to genetically "silence" the protein and reduce the level of RBM3 in cancerous cells. The approach stopped cancer from growing and led to cell death. The new technique has been tested successfully on several types of cancers – breast, pancreas, colon, lung, ovarian and prostate.

"We are excited about this discovery because most cancers are thought to come from mutations in genes, and our studies, for the first time, have shown that too much of this type of protein actually causes normal cells to turn into cancer cells," said Shrikant Anant, Ph.D., a cancer biologist at the OU Cancer Institute and principal investigator on the project.

Anant said they found RBM3 protein in every stage of many cancers, and the amount of protein increased as the cancer grew. The protein helped the cancer grow faster, avoid cell death and was part of the process that formed new blood vessels to feed the tumor.

"This process, called angiogenesis, is essential for tumor growth and suggests that targeting RBM3 may be an extremely powerful tool against many and perhaps all solid tumors," Anant said.

Source: University of Oklahoma

Previously unseen switch regulates breast cancer response to estrogen [Think Gene]

Posted: 08 May 2008 05:38 PM CDT

A tiny modification called methylation on estrogen receptors prolongs the life of these growth-driving molecules in breast cancer cells, according to research by scientists at Emory University’s Winship Cancer Institute.

The results are published in the May 9, 2008 issue of the journal Molecular Cell.

Most breast cancers contain estrogen receptors, which enable them to grow in the presence of the hormone estrogen. Their presence can determine whether tumors will respond to the estrogen-blocking drug tamoxifen.

The finding will help researchers sort out how mutations change the estrogen receptor’s function and allow some breast cancers to resist tamoxifen, says Paula Vertino, PhD, associate professor of radiation oncology at Emory University School of Medicine.

“The problem is that a significant fraction of estrogen receptor positive tumors don’t respond to tamoxifen,” Vertino says. “Development of new drugs that interfere with the methylation of the estrogen receptor may be an alternative way to treat those tumors.”

Until recently, scientists thought methylation enzymes acted only on DNA molecules or on histones, proteins that bundle DNA into spool-like packages. Methylation enzymes add tags called methyl groups to other molecules, influencing their ability to turn genes on or off.

Vertino and her colleagues found that one of the modification enzymes, called SET7, methylates a flexible part of the estrogen receptor. When they created breast cancer cells with reduced levels of SET7, the estrogen receptor molecules lasted only half as long and were less effective in turning on genes.

Vertino’s team showed that a mutation in the estrogen receptor found in more aggressive breast tumors interferes with methylation in cells. Also, the methylation appears in exactly the same spot where another protein called BRCA1 adds a different kind of regulatory marking, and may block BRCA1’s restrictive effects on the estrogen receptor.

Women who inherit a mutation in the gene that encodes BRCA1 have up to an 80 percent lifetime risk of developing breast cancer, several times the risk of those who don’t have it, according to the National Cancer Institute. BRCA1 mutations are estimated to account for about a third of all inherited breast cancers and roughly 2-3 percent of all breast cancers.

Scientists are beginning to look for drugs that could modulate methylation enzymes. Vertino says that methylation probably affects several other proteins similar to the estrogen receptor.

“I expect this will be just the tip of the iceberg,” she says. “Methylation may be just as common as other protein modifications, and even more complicated.”

Source: Emory University

Nonsensical headlines about the platypus genome. [T Ryan Gregory's column]

Posted: 08 May 2008 05:03 PM CDT

I am swamped at present and have not had time to discuss the recent publications about the platypus genome. I had planned to wait and to talk about some interesting aspects, but the headlines are just too crazy to ignore.

[Tomorrow's Table]

Posted: 08 May 2008 04:17 PM CDT

Check out the latest review of Tomorrow's Table

OATP Knock Out Murine Model [A Forum for Improving Drug Safety]

Posted: 08 May 2008 03:14 PM CDT

COMMENT: The mutant in vivo mouse model or the so-called “knock out” (ko) mouse in which a single gene is deleted or disrupted is increasingly used for the exploration of drug interactions. In the case of the OATP transporters, the so-called SLCO or SLC21 subfamily, the mouse has a single hepatic SLCO transporter, the SLC01B2 tranporter, in place of the 2 human hepatic transporters, SLC01B1 and SLCO1B3 which reside on the basolateral membrane of liver cells (the portal vein side) and influx many common drugs including rifampin and pravastatin.

In this article, details are given of how this “ko” mouse was utilized to test these 2 known SLCO substrates. Conjugated bilirubin was modestly increased, but no jaundice was seen in the ko mice suggesting that other liver transporters take up the slack of importing conjugated bilirubin when SLCO1B2 is lacking. The plasma AUC of rifampin in the KO mouse was 1.7 times that of the wild-type and the plasma clearance of rifampin was reduced. Pravastatin was similarly affected. The authors make it clear that mice SLCOs are different enough from humans that an exact comparison remains unjustifiable, but this in vivo animal model is useful for substrate, inhibitor and inducer analysis as well as drug interaction testing.

ABSTRACT:Mol Pharmacol. 2008 Apr 15 [Epub ahead of print] Targeted Disruption of Murine Organic Anion-Transporting Polypeptide 1b2 (oatp1b2/Slco1b2) Significantly Alters Disposition of Prototypical Drug Substrates Pravastatin and Rifampin. Zaher H, Meyer Zu Schwabedissen HE, Tirona RG, Cox ML, Obert LA, Agrawal N, Palandra J, Stock JL, Kim RB, Ware JA.

Organic anion transporting polypeptide (OATP) 1B1 and 1B3 are widely acknowledged as important and rate-limiting to the hepatic uptake of many drugs in clinical use. Accordingly, to better understand the in vivo relevance of OATP1B transporters, targeted disruption of murine Slco1b2 gene was carried out. Interestingly,Slco1b2(-/-) mice were fertile, developed normally, and did not exhibit any overt phenotypic abnormalities. We confirmed the loss of Oatp1b2 expression in liver using real-time PCR, Western Blot analysis and immunohistochemistry. Oatp1a4 and Oatp2b1, but not Oatp1a1 expression was greater in female Slco1b2(-/-) mice, but expression of other non-oatp transporters did not significantly differ between wildtype and Slco1b2(-/-) males. Total bilirubin level was elevated by 2-fold in the Slco1b2(-/-) mice despite that liver enzymes ALT and AST were normal. Pharmacological characterization was carried out using two prototypical substrates of human OATP1B1 and 1B3, rifampin and pravastatin. After a single intravenous dose of rifampin (1mg/kg), a 1.7-fold increase in plasma AUC was observed while the liver-to-plasma ratio was reduced by 5-fold, and nearly 8- fold when assessed at steady -state conditions after 24 hours of continuous subcutaneous (SC) infusion in Slco1b2(-/-) mice.

Similarly, continuous SC-infusion at low dose rate (8 microg/hr) or high dose rate (32 microg/hr) pravastatin resulted in a 4-fold lower liver-plasma ratio in the in Slco1b2(-/-) mice. This is the first report of altered drug disposition profile in the Slco1b2 knockout mice and suggests the utility of this model for understanding the in vivo role of hepatic OATP transporters in drug disposition.




A Challenge for Science Bloggers [Bayblab]

Posted: 08 May 2008 02:24 PM CDT

Skull in the stars has issued a challenge to science bloggers: "Read and research an old, classic scientific paper and write a blog post about it." The suggestion is pre-WWII papers, but I've decided to pick something slightly more recent (pre-Woodstock, instead).

So that's the challenge: Pick a classic, write a post and submit the link in the comments over there so they can all be compiled in one list. Get it all done by the end of May. Have fun!

The New E. Coli: Now With Minty-Fresh Scent. Not At All Like Poo. []

Posted: 08 May 2008 01:43 PM CDT


NPR ran an interesting story about MIT Bioengineering whiz-kids the other day. The really noteworthy angle was that some students didn’t like the smell of their subject, E. coli — too much like, well, poo (duh; they live in our guts and digest our food for us…) So they rather casually cooked up their own transgenic version that smelled like wintergreen — just to make life in the lab more pleasant. An even more interesting wrinkle was their second transgenic mod — to change the smell to bananas when the E. Coli matured.

You tell 'em Arnold! [Discovering Biology in a Digital World]

Posted: 08 May 2008 12:30 PM CDT

Community colleges are such extraordinary places that even California's governor, Arnold Schwarzenegger credits his time at Santa Monica community college as one of the secrets to his success.

From the SF Chronicle:

"People always ask me 'What is the secret of your success?' " he said Tuesday. "I always say, 'Come to America. Go to community college. And marry a Kennedy. It's all very simple.' "

HT to Jim DeKloe.

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Translating ELSI – From a Conference at Case Western to the World [PredictER Blog]

Posted: 08 May 2008 09:17 AM CDT

An exciting conference occurred last week in Cleveland, Ohio on the past, present, and future of research into the ethical, legal, and social implications genetics (so-called "ELSI" research). If the large number of interesting presentations at this conference is any indication, the field is flourishing. Although I saw relatively few presentations (I was only there for part of the conference), the discussions, the turnout, and the book of abstracts show the rigor and creative energy of a thriving, international group of scholars.

As part of a panel on Saturday morning (May 3rd), I presented a short talk entitled "PredictER: Indiana University's Experience in Translating Predictive Health Ethics Research into Practice". The presentation covered the work that we've been doing at the IU Center for Bioethics on the ethical and legal aspects of predictive health research. Other speakers in the same session described similar work under way in Kyoto, Japan and in Newfoundland, Canada. Genetics is truly a global field, and, thus, so is the project of examining the ethical, legal and social implications of the science and medicine. If we want to insure the ethical practice of genetic science and the equitable sharing of its benefits, the global participation exemplified by the work at this conference, must become a common feature in the investigation of the ELSI of predictive health research. – Peter H. Schwartz

How To Make Money Selling Personal Genomic Services [Eye on DNA]

Posted: 08 May 2008 03:34 AM CDT

Given my limited knowledge of how to run a business (my sister’s the Harvard MBA of the family), I’d always thought having a bigger market is the key to success (as I alluded to in my previous post, Using Dispoable Income for Genetic Tests). macbook airThere is, of course, another way of increasing company profits as Steve Jobs demonstrated with Apple:

Apple’s stock has shot up more than 70% over the past year, thanks to Jobs’ strategy of focusing on his most profitable customers and coming up with new things to sell them—the ultra-thin MacBook Air most recently—rather than just chasing more market share. [emphasis added]

~The 2008 Time 100

So what does this mean for personal genomics companies? Perhaps Knome with its $350,000 genome sequencing service isn’t too far off the mark.

NB: If you’ve got an extra $2500 that you don’t know what to do with, check out my list of DNA services you can buy with $2500.

Roundup Deluxe: Every ‘My Genome’ Post From the Start [BUZZYEAH » My Genome]

Posted: 08 May 2008 03:16 AM CDT

my genome categoryThis roundup is mostly for new readers of this blog. It's just a quick snapshot of every post I've published in the 'My Genome' category up until today.

#24 Genetic Testing on The John and Ken Show (May 5, 2008)
#23 Just Downloaded a File Containing my Raw Genome Data. Now What? (May 4, 2008)
#22 Visualization of My Genetic Similarity to People Around the World (Apr 30, 2008)
#21 How Heart Attack and Other Four Star-Rated Topics Relate to My DNA, Part 2 (Apr 24, 2008)
#20 Fun with Y Chromosomes: Exploring my Paternal Ancestry (Apr 16, 2008)
#19 Look Ma, I'm in Newsweek (Apr 14, 2008)
#18 Fun with mtDNA: Exploring my Maternal Ancestry (Apr 12, 2008)
#17 How Breast Cancer and Other Four Star-Rated Topics Relate to My DNA, Part 1 (Apr 11, 2008)
#16 Sharing My DNA Results (Apr 9, 2008)
#15 The Most Common Cancer (For Men) and Me (Apr 6, 2008)
#14 I Just Received an Exciting Email! (Apr 4, 2008)
#13 Bummer… I'm One of Those Customers (Apr 1, 2008)
#12 Still Waiting For My DNA Results (Mar 16, 2008)
#11 Demo 23andMe with the "Mendel Family" (Feb 23, 2008)
#10 We Joined The DNA Network plus Exciting Spit Challenge News (Feb 12, 2008)
#9 Spit Party Photos (Feb 10, 2008)
#8 Spit Challenge: Fill Tube With 2.5ml of Saliva in Under 146sec (Feb 7, 2008)
#7 FedEx Tracking Says DNA Kit Arrives Today (Feb 6, 2008)
#6 Saliva-Spitting 23andMe Party on Wednesday! (Feb 4, 2008)
#5 $1000 Raised! Just Ordered My 23andMe DNA Kit (Jan 22, 2008)
#4 Decoding My DNA Soon, $820 Raised So Far (Update: $1000 raised!) (Jan 11, 2008)
#3 Calling All 23andMe Saliva Spitting Bloggers! (Dec 16, 2007)
#2 Fundraising Updates for Andrew's DNA Test (Dec 12, 2007)
#1 Help Me Decode My Genome by Christmas (Dec 6, 2007)

Subscribe to 'My Genome' posts by  RSS or email.


Featured Articles From The Genetic Genealogist [The Genetic Genealogist]

Posted: 08 May 2008 02:00 AM CDT

I’ve added a new page to the blog called “Featured Articles“. It’s available 24/7 at the top of every page, and contains a categorized list of about 50 of my favorite articles from the last year. These posts are listed under categories including “Popular Articles”, “Personal Genomics”, “Learning About Genetic Genealogy”, “Ethical Issues”, and “Famous DNA”. This easy-to-read format is much easier to navigate than the clumsy “Categories” column in the right sidebar, which returns too many results in no apparent organization. If you’re relatively new to The Genetic Genealogist, you might find some interesting articles that you missed the first time around. Happy reading!

Does anyone have a clue who this could be? [business|bytes|genes|molecules]

Posted: 07 May 2008 10:02 PM CDT

Job Description

You don’t get to see job descriptions like this too often in the life sciences. Have to love the What you get section.

What does the job description tell us. It’s a web-based consumer focused company with a focus on healthcare and with an informatics backend. Comes out of Stanford and has a Nobel prize winner advising it, which sounds very much like Andy Fire (based on the Stanford angle).

Let’s start the speculation.

Guess where I found this position; by tracking ‘bioinformatics’ on Twitter

Technorati Tags: , , , ,


Tired? You May Not Be Getting Enough Sleep [Highlight HEALTH]

Posted: 07 May 2008 09:23 PM CDT

ResearchBlogging.orgA good night’s sleep is increasingly loosing out to late night television, the internet, video games and other modern day distractions, and our health is taking the toll. An estimated 50 to 70 million people suffer from chronic sleep loss and sleep disorders, and loss of sleep is associated with a variety of health problems, including obesity and depression [1]. According to a recent four state study by the Centers for Disease Control and Prevention (CDC), 70% of adults report not getting enough rest or sleep at least once over the past month; 10% report insufficient rest or sleep every day [2].

asleep-at-desk.jpgThe CDC analyzed 2006 Behavioral Risk Factor Surveillance System (BRFSS) data from four states, Delaware, Hawaii, New York and Rhode Island. The study, one of the first to present state-level information on any sleep-related measure, found that the prevalence of insufficient sleep was greater in young adults. Of those ages 18 — 34, 13.3% reported insufficient rest or sleep every day over the past month. Of those aged of 35 — 54, only 10% reported insufficient rest or sleep every day over the past month. The percentage was smallest (7.3%) for those aged ≥ 55 years. Similar trends were observed for shorter periods of time. Interestingly however, for people reporting only 1 — 6 days of insufficient rest or sleep during the preceding 30 days, young adults had the lowest percentage (27.8%), while adults aged 35 — 44 had the highest percentage (38.2%), followed by adults aged 45 — 54 (36%) and people aged ≥ 55 years (31.7%).

Persons unable to work were significantly more likely to report insufficient rest or sleep everyday than people employed, students or homemakers, people unemployed or people retired. With increasing education, respondents were less likely to report no days of insufficient rest or sleep.

The study is subject to a number of limitations. Chief among them is that it uses the results of a survey. The principle limitations of a survey are the validity and reliability of responses. Poor recall, intentional deception and misunderstanding can all contribute to inaccuracies in the data. The survey method is also descriptive and cannot offer insights into cause-and-effect relationships. Lastly, the data only reflects sleep trends in four states and may not be representative of the entire United States. Nevertheless, it is consistent with another CDC study using data from the National Health Interview Study, which found that the percentage of adults at all ages reporting six hours or less of sleep per night increased from 1985 to 2006 [3].

According to the National Sleep Foundation, most healthy adults require 7 to 9 hours of sleep each night [4]. Children and adolescents need even more sleep than adults. Children aged 3 — 5 years require 11 to 13 hours of sleep each night, children aged 5 — 12 require 9 to 11 hours and adolescents require 8.5 to 9.5 hours [4].

Here’s some tips to get a good night’s sleep:

  • Keep your room quiet and dark
  • Make sure your bed is comfortable
  • Avoid or limit caffeine and alcohol consumption
  • Don’t smoke
  • Eat dinner at least 2 — 3 hours before bedtime
  • Relax prior to bedtime
  • Don’t exercise right before bedtime
  • Establish regular bedtime and waketime schedule

Additional information on sleep and sleep disorders can be found at The National Sleep Foundation, Sleep and The Insomnia blog.

The results of this study should come as no surprise, especially to many of you who are undoubtedly reading this late in the evening. How about you? Do you get enough sleep every night?


  1. Institute of Medicine. Sleep disorders and sleep deprivation: an unmet public health problem. By the Committee on Sleep Medicine and Research. Edited by Harvey R. Colten and Bruce M. Altevogt. 404 pp. Washington, DC, National Academies Press, 2006.
  2. Centers for Disease Control and Prevention (CDC). Perceived insufficient rest or sleep–four states, 2006. MMWR Morb Mortal Wkly Rep. 2008 Feb 29;57(8):200-3.
    View abstract
  3. QuickStats: Percentage of Adults Aged >18 Years Who Reported an Average of <6 Hours of Sleep per 24-Hour Period, by Sex and Age Group — National Health Interview Survey, United States, 1985 and 2006. MMWR Morb Mortal Wkly Rep. 2008 Feb 29;57(8):209.
  4. How Much Sleep is Enough? National Sleep Foundation. Accessed 2008 May 6.
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