Canada's impact factor

I ran across some statistics that showed Canada has a pretty decent citations per paper published according to in-cites.com. Apparently after Switzerland, Sweden, Netherlands, England and the United States, Canada has an average of 11.14 citations / publication. That suggests to me that Canadian researchers are producing some quality research publications. The USA publishes WAY more papers than any other country and it's all obviously in English. So perhaps having English as an official language in Canada helps as we publish a lot of papers that may be cited by English speaking US researchers. If you are interested in some better analysis of where Canada sits internationally check out this somewhat old Nature paper (2004, subscription req.) What is disturbing to me is that despite being obviously productive researchers, this is not reflected in the Canadian governments investment in research. We are ranked 14th in health research funding!! Also check out patents granted / capita which is pretty interesting, go Iceland! These stats are of course to be taken with a grain of salt however I still find them interesting.

Cancer Carnival Call for Submissions

The 5th edition of the Cancer Research Blog Carnival is fast approaching, and what better way to ring in the new year. To all those interested in participating and/or reading the upcoming fifth edition, the deadline for submissions is Wednesday, January 2, 2008 (or thereabouts) and the post will be up Friday, Jan 4 here at the Bayblab.

If you have a story regarding cancer research, including (but not limited to) therapeutics, diagnostics, standard care, survivor stories or basic science you can submit a link either in the comments here or the carnival submission form on this site.

I am Legendary Oncolytic Virus

Bad news for those of us who think that oncolytic viruses show great potential as cancer therapeutics is coming out of Hollywood. I haven't seen it but apparently the plot of 'I am Legend' starring The Fresh Prince revolves around an cancer curing virus mutating and killing almost everyone except his Freshness.
From wikipedia (I am Legend):

A genetically reengineered measles virus called Krippen Virus or KV, created as a cancer cure by Dr. Alice Krippen (Emma Thompson), rapidly spreads and wipes out the population of the world by the end of 2009, leaving military virologist Robert Neville (Will Smith) the last human survivor in New York City and possibly the world.

The virus killed 90% of the people on the planet; fewer than one percent are immune. The remaining survivors were infected, initially exhibiting the early symptoms of rabies, but then degenerated into an animal state driven by hunger and blind rage. Neville is watched by these "Infected" people, who react painfully to UV radiation. They therefore avoid sunlight and hide in the dark underground, and in buildings (in groups called "hives" by Neville), swarming out at night. Dogs and rats are also susceptible to the virus. By 2012, Neville has not seen another normal human being since the virus' release three years earlier, and suspects that the Infected have succeeded in killing the remainder of the immune survivors. Neville is outnumbered by the infected and running out of time as he seeks a cure.

Some pretty bad press for a treatment that's just getting out of the gates, and this might be the first time many people hear about the potential of treating cancer with replicating viruses.

Rodeo confusion

Discussion over beers turned to rodeo, specifically bull riding. I thought I had heard that bulls were electrocuted on their testicles just as the gate is opened. This is apparently a mixture of partial truths. The bulls do have a flank strap which some people have thought causes pain to the bull's testicles, however here's the info on the flank strap:
The flank strap is often misunderstood. Its purpose is to entice the bull to kick more. Without it, most bulls would have greater tendency to run or fall. The flank strap serves to regulate their bucking somewhat and cuts down the risk of injury to a bull. If you are familiar with a dog's ticklish spot, then you have an understanding of how a flank strap works. Bulls and horses are notoriously ticklish around the flank area.
There is also an electric shock involved in getting the animals fired up, illegal however in most places. Almost all the information I can find on the internet is about animal rights abuse. Apparently the 'hot shot' delivers 5000volts. It is applied to the rear end of the animal just before the gate is opened. video.
Not quite as bad as getting it straight to the genitals but it sounds uncomfortable. I'm not going to weigh in on the moral issue but I find watching the bull riding entertaining( video -NSFW because of soundtrack = footloose). I think I cheer for the bull though....

Quack of the week (Pt. 2): Water, water everywhere...

What could be better for you than vortexed water with a long energy wave field? Vortexed ALKALINE water with a long energy wave field.

One of the baybs from the Bay sent us this juicy tidbit: The Kangen Water Maker. Behind this slick website is another 'miracle' water treatment that can solve your problems of indigestion, diabetes, obesity, osteoporosis and constipation (among other things). It's good for non-health applications too: artists and painters can expect more vibrant hues and smoother strokes when their paints are mixed with alkaline water! Apparantly Kangen means 'return to original' in Japanese (according to one seller) which is ironic because pure, unadulterated water should have a pH of 7 not the pH 8-9.5 that these guys suggest you drink.

How does it work? The Kangen water maker is basically an electrolysis machine that uses dissolved minerals to acidify or alkalize water. This alkaline water, they claim, contains water molecules that cluster in groups of 5-7 instead of 10-14 like 'normal' water. The theory is that the smaller molecular grouping allows the water to travel to places regular water can't, making it better for hydration and delivery of nutrients. Additionally, they claim that Kangen water alters body pH, which prevents acid build up, an associated leaching of calcium from bone and increase in fatty acid deposits.

Why doesn't it work? Even if you can maintain alkaline water for more than a transient period of time (this is accomplished by adding minerals to the water, which can alter the taste - just think about drinking 'hard' water which is also alkaline) as soon as it hits the strong acids of the stomach any alkalinity will be neutralized. Not to mention there seems to be no scientific evidence that this clustering effect is real or that it would be anything more than fleetingly transient. Most studies support the idea of a dynamically changing, disordered water structure. Not to mention that there are water quacks out there who pitch acidic water or water with LARGER clusters as the true 'healing' water.

Of course this has all the standard hallmarks of quackery to go with the pseudoscience: untested medical claims and large disclaimers about lack of FDA review. Some sellers are part of multi-level marketing schemes, and one goes so far as to combine his selling of water ionizers with marine phytoplankton for 'the best whole food nutrition available' and our pet favourite StemEnhance.

For a more in-depth analysis of the pseudoscience of alkaline water, this chemist from SFU does a pretty thorough debunking.

Bayblab Podcast Episode 14

The famous bayblab podcast is now full of holiday cheer and back where it belongs: at a pub! This time we discuss what's new in cancer research, talk about the psychology of quacks who sell fake stem cell remedies and reveal shocking lab tales of promiscuity in the dark room which may explain why Bayman is absent.

Quack of the week: Healing Water Online

In our last quack of the week, Kamel exposed companies selling algae found in pond water, and claiming they could harness the power of your stem cells. This week I found an even more impressive treatment: tap water. That's right someone has found a way to sell you tap water with the premise that it will heal you. And it's not even Coca-Cola.

Here is the explanation. First you have to accept the fact that genes do not control life. That's a lie. We just repeated it for so long that that we have come to believe it is true. But apparently it was never tested scientifically. If you don't believe me, watch this video. The quack behind this video is Dr. Bruce Lipton, who apparently was teaching medicine at the University of Wisconsin. He also wrote a book called the "Biology of Belief", which is a deceptive title since it's actually about changing your own biology with your mind. The irony of which seems to be lost on the author. Apparently he's also pretty much discovered epigenetics, which if you were not aware explains how energy from the mind alters protein expression.

While lots of nutjobs seem to love the book, there are few amusing reviews on amazon such as this one by a Columbia University researcher:

"Furthermore, Dr. Lipton claims that illness can be cured by mere belief. This isn't only nonsense; it is incredibly unprofessional and irresponsible. This is the equivalent of a TV Evangelist banging his palm against the foreheads of cancer patients, pushing them back down in their seats and proclaiming them cured, only to then say later to an investigating reporter who mentions that the patients later died that the Lord's magic stopped working because doubt entered into the hearts of the disbelieving patients. What an incredibly cruel sentiment. "

Which brings me back to water. Dr Lipton's ideas have inspired the creators of "Healing Water Online" because apparently your mind can also alter water and vice-versa. Now I'm sure a cold shower can elicit some spiritual experiences in some people (I highly recommend that link). In fact I often praise the lord when somebody flushes while I'm in the shower. But this is different. Somehow, this has to do with the energy you can produce with your mind, and the unique properties of water. For example did you know that:

"Water's reputation as a powerful solvent derives from its ability to absorb energy vibrations and its particular electromagnetic and chemical qualities, being able to break down substances into their constituent parts. Naturally flowing water creates complex structures: micro clusters of vibrating energy centres, constantly receiving and transmuting energy from every contact the water body makes; and laminar structures which generate energy from the interaction of the planes against each other."

So how can I harness this power you ask? Well it's easy, you just need to buy a $144 jug that has a propeller inside. Why? Well isn't obvious by now:

"The compact motor housed in the lid of the 2-litre jug drives a left-turning silver propeller wich forms a beautiful vortex throughout the depth of the plain tap water for 3½ minutes; this re-enlivens, restructures, reoxygenates and purifies the water by the spiral movement alone.
The energy wave field of normal tap water is 35 cm; Living Water Vortex Jug's is 2,4 metres! A healthy person has an energy wavelength of about 1,9 metres, and as a person consists of 75% water, s/he will be regenerated by the greater energy of restructured water."

Wow what a deal. That's almost a 26% increase of your wavelenght, or only 88 cents per centimeter! And they also suggest you combine your healing water with long distance healing. That's right, for only $44 they will channel energy to you, sorta like what kamel's power to make people dumb at a distance. Actually it's exactly like that.

Songbird speech

Just ran into this paper that knocks down FoxP2 in songbirds. We've mentioned FoxP2 before on the bayblab as it is necessary for proper language development in humans. And indeed these songbirds are unable to properly imitate songs after knockdown of FoxP2 in a particular brain area. This really strongly suggests an evolutionary relationship between bird songs, (at least learned bird songs) and human language. An animal model for language development = Cool.

Favourite cell lines & Cedarlame

I was curious as to what were the most popular cell lines. Personally I'm a big Hela cell fan. They are ubiquitous and you don't have to worry about Hela cell contamination of your Hela cells. Many key experiments were done in Hela cells so it doesn't feel like you are using a random cell line where cell line specific artifacts are unimportant.
Any other nominations for favourite cell lines?
MEFS, HFFs??
I sent an email to ATCC asking for a "Top Ten most popular cell lines" and they replied with a LAME response:

Dear Rob:

I am writing from Cedarlane Laboratories, which is now the exclusive
distributor of ATCC products within Canada. Your query regarding top ten
cell lines from the ATCC has been forwarded to us.

ATCC cannot provide the information that you have requested because it
is proprietary.

Thank you,
Cedarlame

Turning Mouse Tails Into Replacement Blood Cells for Sickle Cell Anemia

Induced pluripotent cells (iPS) have been garnering lots of attention (and papers) lately, since it was first shown that adult fibroblasts (and since then, skin cells) can be reprogrammed to pluripotency by forced expression of a handful of genes. Despite much speculation, it has remained unknown until now whether these cells are actually be good for anything, therapeutically speaking.

While it remains to be seen whether iPS can give rise to autonomous souls, Jaenisch's groups has now shown that iPS can be applied therapeutically. They derived iPS from the tail fibroblasts of sickle cell anemia mice, fixed their genetic deficiency ex vivo, differentiated them into hematopoietic progeintor cells and transplanted them back into the affected mice to restore a functional pool of red blood cells. Pretty damn cool.

Smoking with Friends

Just ran into this amazing factoid on the latest WNYC Radiolab podcast. Apparently "social isolation" is as risky as smoking for increasing your mortality. Unreal. Maybe however it has more to do with the particulars of the social circle you are in, ie no friends is bad, but maybe your particular friends are just as bad for you as no friends. Especially if you are getting some second hand smoke from them.
Just when I thought that social isolation was a cheap and easy alternative to cigarettes.

Supernatural Science at the BMI Department?

The Biochemistry, Microbiology and Immunology (BMI) department of our university publishes a bi-weekly newsletter for the grad student body. The latest edition, Issue 57, includes an article entitled "Specializing in the Natural and Supernatural Sciences: An Interview with Jason Tetro" (the latest issue can usually be found here but has not yet been posted at the time of this writing). The article profiles a student of the department who has a hobby (and side-job) of tarot card reading.

Personally, I don't care what people believe or do with their spare time, but for a publication of the BMI Grad Student Association to spin and legitimize tarot card reading and the supernatural as science is embarrassing for me as a member of the department. The following is our response sent to the editors of the publication:

Dear Editor,

RE: "Specializing in the Natural and Supernatural Sciences"

Science is the investigation of physical and natural phenomena through observation and experimentation. The supernatural, by definition, is unexplainable by natural law and falls squarely oustide the scientific realm.

I understand the desire to profile members of the department and, as an author of the science blog "The Bayblab", I understand that it can be difficult to come up with ideas for stories. However, a profile of the *scientific* acheivements of the student, or even a critical analysis of research articles (the references of which were omitted) mentioned in the interview, would be more appropriate. (Incidentally, we at the Bayblab devote a considerable amount of energy to promoting critical thinking and distinguishing between science and pseudoscience or quackery.)

To include an article in the departmental bulletin about the supernatural and classify it as science is a disservice to your readers and a disservice to the reputation of the department as a scientific body.

Kamel, Rob
http://bayblab.blogspot.com

Marilyn Kozak, professional critic

I think every field needs a solid critic like Marilyn Kozak. We are talking about THE Kozak of the "Kozak consensus sequence fame". She has published a few papers on criticizing the field of internal ribosome entry sites (IRESs). Her lastest is still critical of the existence of viral internal ribosome entry sites which have not only studied for quite some time now but are used as molecular tools for expressing multiple genes from one mRNA. She is persistant. Here is an older response from some scientists in the field to some of her critisisms. Despite being perhaps frustrating to those in the field it is probably good to have such a dedicated (and famous) critic to point out shortcomings in the published data. I wish there was one in my field, at least just for entertainment purposes.

Cancer Research Blog Carnival #4 is UP!

This edition is by far the best one so far. I really feel like it's taking off. Well worth the read if you're interrested in cancer research, with quite a mix of topics such as VEGF immune therapy, nestin in prostate cancer, cancer vaccines, radioimmunotherapy and much more! Ben again did an incredible job of hosting. If you would like to host the next edition, or submit a post, check out this link. Special thanks To Ben for also designing a new logo for this carnival!

Reading through nonsense

We recently heard a solid journal club presentation about genetic nonsense mutations. Nonsense mutations are point mutations in the DNA sequence that introduce a premature stop (or nonsense) codon and can lead to a truncated protein (or, in many cases, no protein at all as nonsense codons are detected by the presence of exon-junction complexes and the mRNA is degraded). The paper discussed described a drug, PTC124, that is entering the final phase of clinical trials that supresses premature termination and allows readthrough of nonsense codons by the translational machinery and production of a full-length protein.

What does this have to do with cancer? The paper discusses the therapeutic potential of the drug in terms of cystic fibrosis and muscular dystrophy - two diseases with pathology known to be caused (at least in some cases) by nonsense mutations in specific genes; CTFR for cystic fibrosis and dystrophin for muscular dystrophy. An obvious target for cancer therapeutics is p53. The p53 gene is mutated in over 50% of human tumours and of those mutants, almost 8% are nonsense mutations (source:IARC p53 mutation database). Research has shown that reactivation of p53 has therapeutic potential in mouse models of cancer, leading to growth arrest and regression of tumours. One need not limit this idea to p53. Nonsense mutations in many other genes, such as BRCA or Rb, have been associated with cancer and bypass of nonsense-mediated decay represents an interesting area to explore when dealing with cancer, and other, therapeutics.

Noam Chomsky quote of the day

Since we're discussing the freedoms of being graduate students and the responsibilities of "speaking truth" as intellectuals (if you want proof of that check out how Kamel's wit triumphs over ignorance in the 100 or so crazy comments of this post), I thought I would bring up this quote from Chomsky, one of the leading intellectuals of this era:

"Students are at a stage of their lives where these choices are most urgent and compelling, and when they also enjoy unusual, if not unique, freedom and opportunity to explore the choices available, to evaluate them, and to pursue them. [...] Well, there are really some moral truisms. One of them is that opportunity confers responsibility. If you have very limited opportunities, then you have limited responsibility for what you do. If you have substantial opportunity you have greater responsibility for what you do. I mean, that's kind of elementary, I don't know how it can be discussed. And the people who we call 'intellectuals' are just those who happen to have substantial opportunity. They have privilege, they have resources, they have training. In our society, they have a high degree of freedom-not a hundred percent, but quite a lot-and that gives them a range of choices that they can pursue with a fair degree of freedom, and that hence simply confers responsibility for the predictable consequences of the choices they make. "

Welcome to Gene Genie!

Welcome to the 21st edition of gene genie! In this edition we cover everything from selection constraints on the evolution of the vulva in nematodes, to the importance of the insertion site in transgenic and the history of microarrays...

Gene

Greg Laden presents The Nematode Vulva and the Nature of Evolution. Greg explains how the vulva can be used as a model in comparative genetics to determine whether evolution is primarily governed by selection and/or selection-independent constraints, not stochastic processes such as drift in unconstrained phenotypic space. He concludes that evolution is more deterministic than stochastic.

96well presents Where do you express your transgene? posted at reportergene.com. This post does a good job of explaining one of the biggest problems with transgenics, namely how poorly we understand integration. The transgene can integrate in any place in the genome and be subject to tissue-specific chromatin remodeling which may render results uninterpretable. One way around this is to target insertion near the beta-actin gene as the author explains: "Recently, the lab of Bernd Kinzel (Novartis), published a technology report in Genesis (vol.45), in which the locus of beta-actin was identified as a good dock for gene expression. Beta-actin is a cytoskeletal building-block expressed in almost every mammalian cell, and it is necessary for life, so only heterozygous transgenic can be developed."

other

FitBuff presents What Is Healthy? posted at FitBuff.com's Total Mind and Body Fitness Blog. FitBuff is asking the question "What is healthy"? At first, this may seem like an easy question to answer. However, when you actually stop and think about it, it's not easy at all... here is what he thinks: "In my opinion, healthy is following a positive lifestyle; one that is manageable, as stress-free as possible, involves the eating of several small meals throughout the day (including lean protein, complex carbohydrates, and healthy fats), incorporates a workout program that is realistic and consistent, and always ends with a good night's sleep."

Techniques

AJ Cann presents DNA Microarrays posted at MicrobiologyBytes. AJ gives us a good primer on how microarrays work along with some educational videos.

That concludes this edition. Submit your blog article to the next edition of gene genie
using our carnival submission form. Past posts and future hosts can be found on our blog carnival index page.

Graduate research: is it school or work?

Here's an Opinion piece posted on behalf of Joel:

"I had an interesting (mostly one-sided… sorry Laura) conversation yesterday, which has led me to write a little opinion-piece.

I obtained my first research experiences working in a basic biology department at a small university. I was lucky enough to find a phenomenal mentor and get some experience in molecular biology in a department with a faculty that focused mostly on ecology, fish biology, teaching, and (for many tenured profs) reading the paper while waiting-out the years until retirement. The graduate students that I worked with were paid primarily by the department; however, they had to earn their living wages (which amounted to about $12,000 a year). They worked as TAs for 2-3 afternoons a week and marked lab reports for at least 10-15 hours every week. They did this to have the opportunity to do research. Similarly, graduate students in basic science programs throughout Canada are paid very little; they also need to TA and to mark reports to earn it. Therefore, they do their research in what amounts to spare time. Although it makes doing their research difficult, it gives them independence. They are not employees of a prof, they are students; they learn in their chosen lab, work on projects that are within the scope of the research interests of their PI, but tailored to their own interests and goals. This should sound familiar: it’s called being a grad student.

In Ottawa, particularly at the OHRI, we are paid comparatively well, and asked only to do our thesis research in return. However, our salaries (unless externally-provided) are paid by our PIs, through their grants. I found the research environment very different when I arrived in Ottawa. People here refer to their PIs as “boss”. They call their research “work”. I have always rejected the term boss for my PI. He is my mentor; I’ll even go as far as to call him my “thesis supervisor”, but never my boss. I don’t go to work. I go to the lab. This matter of semantics has been my private rejection of a system that I have never been able to understand.

To me, a PI has a specific role. They obtain funds to work on projects that they find interesting. They recruit like-minded people to help them work towards their research goals. The PI obtains funds, and thus has responsibilities to both the providers of funding - to ensure that the money is well spent - and to the people that work in their lab, to ensure that they are able to pursue their research in a good environment. This is where the formal authority of the PI ends for me.

Graduate school is a learning experience, not a job. Any PI that tries impose hierarchical ruling on a graduate student (outside of the realm of authority that I described above), is not only exercising unwarranted power, but is also harming the potential of the project and the student. Creativity and invention are what makes good research great research. When creativity is stifled, mediocrity is inevitable. Whenever such unnecessary imposition of force is encountered, it should be rejected and fought. However, it is so pervasive in Ottawa that all incoming graduate students undergo a form of indoctrination that keeps them from questioning the role of their mentor in directing their day-to-day activities.

I will finish with an excerpt from a biography of James Watson (maybe not the greatest role model for potential PIs, but a man who often makes some great points and who obviously achieved great things in his mentoring and administrative careers):

“(Watson’s students and post docs) knew that they were working “primarily to advance their own careers.” Though terrified of Watson, they weren’t working for anyone but themselves. “I never worked for anybody,” Watson recalled on his 60th birthday. “I could never work under others. You only get somewhere with people if they feel they are working for themselves”."

Carnival season

To all those interested in participating and or reading the upcoming fourth edition of the Cancer Research Carnival the deadline for submissions is Wednesday and the post will be up Friday on Ben's blog... Also for those of you looking for the Gene Genie carnival, my bad, it's a day late but it will be up sometime later today.

Want to join the 200 mile high club?

As a joke in my lecture about sperm motility I mentioned some experiments made in space by NASA which have shown that sperm is more motile in microgravity and less motile in hypergravity (high G). There had been numerous rumors that Leica wasn't the only one to have gone doggy style in space. It is now confirmed that both Russians and Americans have joined the 200mile high club. The result: only 4 positions are possible in space, the rest is left to the imagination...

"Twenty positions were tested by computer simulation to obtain the best 10, he says. "Two guinea pigs then tested them in real zero-gravity conditions. The results were videotaped but are considered so sensitive that even Nasa was only given a censored version."

Only four positions were found possible without "mechanical assistance". The other six needed a special elastic belt and inflatable tunnel, like an open-ended sleeping bag.

Mr Kohler says: "One of the principal findings was that the classic so-called missionary position, which is so easy on earth when gravity pushes one downwards, is simply not possible.""

Too bad it's a hoax. When is NASA going to concentrate on some real priorities that people actually care about ;)

Paedophiles are left-handed

I can't think of a group of people more despised by society than left handed people. Well, not surprisingly, not only is pedophilia associated with low IQ, they are three times more likely to be left handed. (read the whole article, it's there, along with some interesting information that indicates this awful sexual disorder has a physiological basis.) The corollary of which is left-handed people are three times more likely to be pedophiles. We all must suffer for the existence of left-handedness, even to the extent that a newly proposed law in Manitoba suggests not reporting left-handers to the appropriate authorities could result in up to two years in jail.

Pro-Probiotics or Anti-Probiotics

We all know that there are some pretty essential bacteria that make up our intestinal flora. So the idea behind probiotics is that you can replace or enrich or modify the beneficial bacteria in your body by eating them. It does seem amazing that bacteria can survive the harsh environment of your stomach but apparently they can be recovered from your feces.
The data to data do indeed suggest that if you have rotavirus induced diarrea probiotics may definitely be helpful. And collegenous colitis, which is difficult to treat, may be slightly relieved with probiotics. And a big one, irritable bowel syndrome (IBS) may be treatable using B. infantis (that is the bacteria that are largely found in the intestines of human infants)
Unfortunately since bacteria are pretty easy to make, and they are already in your food like yogurt and other fermented milk, anyone can make something and call it probiotic. And of course it is suggested that we all need it and that it is a general 'cure all'. For instance this manufacturer states that:

Factors that lead to overgrowth of pathogenic bacteria:

• Poor eating habits – especially sugar and refined foods
• Chlorinated drinking water
• Stress, aging and disease
• Born by caesarean section
• Alcohol consumption
• Bacterial infections
• Traveler's bugs
• Antibiotics in food production or prescription medications

While I don't know for sure that any of these are wrong, (born by cesarean does seem strange whereas bacterial infections is redundant), I don't think that anyone can say that probiotics can help with all pathogenic bacteria.
So maybe probiotics are great for some conditions and maybe we should all be eating more yogurt but I don't know if eating a bunch of lyophilized bacteria is going to make me 'feel better.'

James Dewey Watson Quote of the Week

"But I guess I owe most of all to Francis, who really did look after me, and who often tried to keep me from being silly. I wasn't as silly as he thought, but he was so sensible that I had occasionally to say things I didn't believe, to see if I could trap him. And I sometimes did".

Nature, 302, 21 (April 1983): 652.

Do you know your cell lines?

We all work with various cell lines. Sometimes those have been in the lab for a long time. Sometimes they are older than you. So how do you know you're still working with the right cell line, that the passaging hasn't completely changed the properties of the cell or that worse, they have been contaminated with another line. I vividly remember a talk from an older well respected researcher who candidly recalled how she wasted years studying a strange cell that happened to be a hybrid of her cancer cell line and a mouse fibroblast cell. Even the HeLa cells, the bread and butter of cell biology, are know to easily contaminate other cells lines:

"Because of their avid adaptation to growth in tissue culture plates, HeLa cells are sometimes difficult to control. For example, they have proven to be a persistent laboratory "weed" and they can contaminate other cell cultures in the same laboratory, interfering with biological research. The degree of HeLa cell contamination among other cell types is unknown, because few researchers test the identity or purity of already-established cell lines. It has been demonstrated that a substantial fraction of in vitro cell lines - approximately 10%, maybe 20%, are actually HeLa cells, due to the fact that the original cells in the cell culture have been overwhelmed by a rapidly growing population derived from HeLa contaminant cells. Stanley Gartler in 1967 and Walter Nelson-Rees in 1975 were the first to publish on the contamination of various cell lines by HeLa."

And recently the TE-7 which have been used for over 20 years as an esophageal cancer model, were found to be a completely different cancer. This has led to the proposal that all cell lines be continuously tested:

"He said the best way to get scientists to comply would be to withhold research grants and publication in scientific journals unless their research used authenticated cell-lines. This verification can be achieved using a technique of DNA profiling which compares the cell-line with a list of known contaminants and can cost as little as £180 per sample. "

Paranoid or justified?

HIV - Out of Africa, via Haiti

The origin of HIV in North America has been a hotly contested issue. It's had conspiracy theories (the Nazi's invented it, it was designed by a pharmaceutical company to kill off Africans), African origin theories, biblical theories (Gods punishing homosexuals) and many many others.

Well, it seems we're a significant step closer to actually telling where the heck HIV did come from.

HIV was first formally described around the 1980's, but it was believed that the first cases (Robert R, famously... a possible African-American rent-boy from LA) were around the 1968 mark.

Well, the news is now out. It seems that it was no coincidence that initial 'outbreak' in the USA was among Haitians. Using new mutation analysis techniques, a group from the University of Arizona in Tucson has now identified the path of the virus by analysing a number of old stored samples from that initial outbreak. The current new hypothesis is that the jump from simians to humans occurred around the 1930's, making the 'big' jump from Haiti to the USA around 1969 (give or take a year, apparently). Their paper has a neat little diagram showing where the virus went, how the virus has spread. Infact, their consensus data is pretty convincing, and seems like they have definitively nailed this little link down.

The final implication of all of this is that HIV must have been floating about in the USA for about 10 years before anyone actually clued up that something was up. Furthermore, there is plenty of evidence that there were several good cases in the mainland USA (Los Angeles, Detroit, Chicago, New York etc) for some time before the first case was identified.

What else could we be incubating?

Ethical "Embryonic" Stem Cells from Your Skin

First it was mouse fibroblasts, and now human dermal fibroblasts have been reprogrammed to have pluripotent ES-like potential. Again, as in murine cells, ectopic expression of the fantastic transcription factor foursome of c-myc, Sox4, Klf4, and Oct3/4 will do the trick. Alternatively, Klf4 and c-myc can be substituted with Nanog and Lin28. Either way it's personalized stem cells from your skin. I'm going to get to work on mine right now...

Holy Freaking Heterogeneous Ribosomes!

Once again I have Palazzo to thank for pointing out a cool paper - this one from Pam Silver's lab, showing that different paralogous (duplicated) yeast ribosomal proteins are involved in translating different messenger RNAs. Since there are some 60 or so duplicated ribsomal proteins, this suggests a huge possible amount of ribosomal heterogeneity in the cell. Ribosomes are not all the same - even in basic subunit structure -and this might be an important piece of the translational regulation puzzle. The authors go on to point out the parallels between this situation and that of histone proteins, which can also bind nucleic acid, are also highly duplicitous in yeast, and also highly subject to regulation through post-translational modification. Thus they propose that if there's a "histone code" that regulates transcription, there may also be a "ribosome code" that regulates translation. Personally, I don't see the evidence that either sort of code exists (vague speculation about codes usually strikes me as an easy way to score sexy points), but there's certainly something interesting going on here.

More interestingly, we recently had a great journal club about the evolution of paralogous histone-modifying enzymes in yeast. The paper examined the evolutionary balance between redundancy and diversity of function in duplicate gene pairs, and showed that functionally distinct (non-redundant) paralogues can compensate for their partner when, and only when, the other is deleted. Presumably then, a similar evolutionary dynamic could be at play in the evolution of ribosomes and the regulation of translation in general.

Speaking of histones, if there's no such thing as histone code, maybe it's more of a universe. The complexity of chromatin structure is unbelievable. What's even cooler is that it's dynamic. So not only is chromatin complex, it's ALIVE. At least that was the impression I took away from a recent talk by Ottawa chromatin mapper Marjorie Brand. Check out her lab's latest paper on how spreading of chromatin-associated MLL protein mediates communication between a distal upstream activator element and the B-globin promoter during differentiation.

Another random factoid that was mentioned in the first paper, and news to me: the yeast (S. cerevisiae) arose from a massive whole-genome duplication, but eventually all but 10% of duplicated genes were lost. Weird. Was the initial duplication event selection-neutral for the original yeast cell it occurred in? Hard to imagine, since I would think two genomes take longer to replicate than one, not to mention the structural instability associated with having all that homologous DNA around. So what's the advantage? Not much, if most duplications were eventually lost. Doesn't this say there was indeed a fitness cost to having extra copies of all those genes if they were ultimately weeded out by selection? The only thing that makes sense to me is if the cost/benefit of duplicate genes has varied over yeast evolutionary time. So it was advantagenous to have backup gene copies back sometime in ancient history, but then became unnecessary or cumbersome more recently. Maybe the environment or the yeast's response to it changed. For example, maybe at one point gene inactivation via radiation-induced DNA damage was a big problem for yeast, so it was often useful to have a backup genome copy around. Then, either environmental radiation diminished or yeast evolved a system for preventing or repairing DNA damage, and they no longer needed to keep the backup genes around. I suppose another possibility is that it has something to do with the role of sexual reproduction..........

Alas, I rant like a raving lunatic. Someone set me straight.

When a "Minor" Species is Not so Minor: The Discovery of mRNA

One of my favorite features out there on the blogosphere, John Dennehy's Citation Classic of the Week, this week discusses the story of a somewhat obscure paper that reports the author's rather unwitting discovery of mRNA. Volkin and Astrachan managed to detect incorporation of radioactive phosphorus into the RNA fraction of phage-infected E coli, into molecules whose base composition resembled that of phage DNA molecules. Judging from their discussion of the results, they didn't really seem to immediately appreciate the true significance of what they had found. Interestingly, people at the time were hung up on the fact that abundant ribosomal RNA was likely the protein-encoding message, rather than this "minor species" of "DNA-like RNA" that Volkin and Astrachan had detected. Naturally, none other than a super-team of molecular biology super-heroes, Brenner, Crick and Monod, saved the day and put it all together: based on the data of Volkin and others, this minor species was indeed the messenger nucleic acid that directed protein synthesis. Read more about the affair over at The Evilutionary Biologist.
(Above figure is from Volkin and Astrachan, Virology, v2 pg. 149 (1956).

10 simple rules to be a sucessful scientist

PLoS has been running a series of editorials about simple rules to follow in research. For example you can check out the 10 simple rules to publishing, to getting grants, for reviewers, for post-doc'ing, collaboration, oral presentation and poster presentation. I just wish they had one for teaching, as I'm facing my first class tomorrow.

The culmination of this series are the 10 rules to do your best research:

1. Drop modesty (strive for excellence)
2. Prepare your mind (luck favors the prepared minds)
3. Age is important (research strategies should be different depending on your age, although I'm not sure I agree with that one)
4. Brains are not enough, you also need courage (I assume this means taking risks)
5. Make the best of your working condition (don't let your environment limit you, but exploit the advantages you have)
6. Work hard and effectively (all the successful scientists I know are workaholics)
7. Believe and doubt your hypothesis at the same time (so be skeptical and accept data for what it is, but don't give up on ideas before you test them)
8. Work on the important problems in your field (work on something interesting and relevant, no matter what the current trends are)
9. Be committed to your problem (because it might take a looong time to solve it)
10. Leave your door open (interact as much as you can with other people, you never know where the insights might come from)
    

Jaenisch On Iran

Rudolf Jaenisch, arguably the foremost stem cell researcher in the world, certainly doesn't shy away from politics. Last time I saw him speak, his lab had engineered the "ethical" stem cell, but he also dedicated quite a few slides to ridiculing US anti-stem cell research policies. Now he's tackling American anti-Iran extremism, with this article on his recent trip to a stem cell conference in Tehran:

"Delays and setbacks are built into the scientific process no matter where it occurs, but researchers in Iran face an additional burden imposed, largely, by politics. Cell biologists lack even the machines that sort cells by surface-protein markers because the necessary US-made equipment cannot be imported. They cannot perform many experiments that we consider routine, but rely on collaborators who have the necessary equipment. Even when equipment has been procured, Iranian researchers face logistics that prevent them from getting on with their experiments.

It seems to me that these restrictions are not in anyone's interest. Scientists themselves exacerbate the situation, fuelled by misinformation that they put themselves at personal risk by travelling to Iran. Of course, people who would not be able to refrain from political discussion or dress as expected would be wise not to go. But the vast majority of scientists would find themselves surrounded, as I was, by courteous, hospitable, well-informed men and women who relish interaction with other scientists. Unfounded apprehensions about the risks of travelling to Iran effectively add a scientific embargo to the politcal one.

"There are clear differences between our countries, but these fade in the laboratory as we approach scientific questions. Furthermore, attitudes and policies that stifle scientific work and collaboration hinder not only science, but also international relations. When we don't have an exchange of ideas, we foster fanaticism and intolerance; this is something that science could help to counteract."

I think it's commendable that Jaenisch has the guts to take positions that powerful people in his country might disagree with, rather than bury his head in the sand alongside many of his colleagues.

PINK EYE outbreak

I love it. There is a bit of conjunctivitis (aka pink eye) making it's way through the lab in which the bay is a part of. It may be that it is from microscope eyepieces, so I wanted to see what I could find on other experiences with this, but I couldn't really.
I did find one person on a forum who said they have encountered pink eye contaminated eyepieces, not once but twice.
I also found out that breast milk cures pink eye. I'm skeptical.
I think one of the reasons I think it's funny is because it's such a childhood thing and one of the funny scenes from "Knocked Up" indicates it can be caused from farting on someone's pillow.
I'm sure I'll think it's funny until it infects someone in the bay.

The Bayblab Pumpkin Brewing Project

In anticipation of our 100000th page load (today!), to celebrate Hallowe'en and just because this is the kind of thing we do here in BayNation, we decided to concoct a special brew. And so began the Bayblab Pumpkin Brewing Project - (BP)^2**

In the fine tradition of marrow rum and in keeping with the season, a pumpkin was chosen as the fermentation vessel of choice. On Hallowe'en night, a small hole was bored into the top of the pumpkin and it was inoculated with a package of baker's yeast, some sugar and a healthy dose of spookiness. The pumpkin was then filled with water and left to ferment at room temperature.

One week later, on the notably less spooky 7th of November, the pumpkin brew was deemed, by arbitrary measure and impatience, ready for tasting.

Tapping the keg: AC makes the first cut

The usually clean Rob, splattered with a mix of pumpkin and baby vomit

Once the pumpkin was cracked open, the yeasty aroma of our brew and the foul stench of evil filled the air. What does evil smell like? As one bystander put it: "It smells like cheese beer." Spectators were simultaneously turned away in disgust and drawn to the spectacle.

Pumpkin ale, or portal to hell?


The resulting liquid

Filtering out the filth

The liquid inside the pumpkin was deemed too 'chunky' to swig fresh from the fruit, so it was put through a coffee filter before tasting. While AC and Rob argued over safety (and who would drink first), I took a sip of the filtered brew. It passed the first test: I didn't keel over. Despite the stink, it was drinkable. It was what I imagine watered down dough put through a blender would taste like. Slight pumpkin overtones. It didn't taste good enough to drink enough to get a buzz given the low alcohol content. This was more bread than beer.

Rob and an uncowardly Coward contemplate the pumpkin ale

Anonymous Coward reacts as Rob takes a healthy swig, while a bystander looks on in disgust

Rob was unsatisfied with the weakness of the drink, so he braved drinking the unfiltered swill. My recommendation for Pumpkin Project 2.0: skip the water, let the natural pumpkin liquids provide the base and let it ferment longer. Of course we still wanted to see what the inside of the pumpkin looked like, so we cracked it right open and let its full bouquet permeate the Bay.

The pumpkin innards and remaining brew

A handful of the resulting goo

Most of the pumpkin innards had pulled away from the shell of the fruit and partially liquefied. Have we stumbled upon a quick and easy way to clean a pumpkin for carving? the inner surface of the pumpkin had softened and was covered with yeasty growth. All drinkers survived the experience, but adjustments need to be made for a successful recipe.

**The Bayblab encourages attempting this experiment at home and posting the results here but takes no responsibility for any injury or illness - physical or mental - that may occur.

Creation museum revisited

I know, I know, it's old news by now, but if you want a good laugh check out this guy's review of the museum... Sample after the break, (and that's only the first paragraph!) :

"Imagine, if you will, a load of horseshit. And we’re not talking just your average load of horseshit; no, we’re talking colossal load of horsehit. An epic load of horseshit. The kind of load of horseshit that has accreted over decades and has developed its own sort of ecosystem, from the flyblown chunks at the perimeter, down into the heated and decomposing center, generating explosive levels of methane as bacteria feast merrily on vintage, liquified crap. This is a Herculean load of horseshit, friends, the likes of which has not been seen since the days of Augeas."

Obstacles to Open Publishing

Palazzo leads a nice little discussion on obstacles to "open access" publishing, based on a conversation with Cell editor Emily Marcus. Many would like to see some sort of Utopian free-love, open-access, internet-based scientific publishing world, but at what cost?

A good time to be a gene hunter

Two interresting mutations have popped up this week. Unfortunately neither will turn you into a hero...


This man has some kind of mutation which rendered his immune system unable to control the warts growing as a result of an HPV infection. Another reason to get the HPV vaccine! The doctors have proposed to use high doses of vitamin A to stop the warts, and remove the rest by surgery.


This 7ft tall 12 year old, had all his teeth by 4 months and was already has big as a 12 year old by the time he got to kindergarden. This is not a case of gigantism, which occurs because of pituitary tumours excreting too much growth hormone, rather this seems to be a new kind of mutation. Joining the 50 or so different genetic syndromes which cause excessive growth such as:

"Extra sex chromosomes (beyond the normal two) with therefore extra copies of the SHOX gene (beyond the normal two) usually results in enhancement of height growth. The most common of these karyotypes are 47,XXY (Klinefelter syndrome), 47,XYY, and 47,XXX. The added height increment is usually modest.

A very rare but more extreme version of "eunuochoid" tallness occurs when a mutation of the estrogen receptor reduces the response of the bones to estradiol. Estradiol is a byproduct of testosterone in both males and females, and is the most potent accelerator of bone maturation and closure known. If a person fails to respond to estrogen, growth can continue until late-20s or longer, and the affected person can reach 8 feet or more in height. Estrogen resistance is the only other endocrine condition that can rival growth hormone excess in producing gigantism. In contrast, the tallness associated with the more common androgen insensitivity syndrome averages only a few inches, as estradiol is not produced directly but rather through conversion from androgens by aromatase.

Marfan syndrome is an uncommon genetic disease due to an inherited defect of connective tissue. In addition to moderate tallness, persons with this condition usually have a slender body build with unusually long fingers (arachnodactyly). Many can also develop a dislocaton of the lens of the eye or, more seriously, a progressive deterioration of the walls of the aorta which can result in sudden death in adulthood. It is usually inherited as an autosomal dominant trait.

Sotos syndrome resembles acromegaly in its mild distortion of facial growth. In addition to tallness, the chief characteristics are large head size, slow development, and autosomal-dominant inheritance."

Sweet Reads

Having just completed James Watson's Avoid Boring People: Lessons from a Life in Science (highly recommended, however you feel about his antics), I am fortunate that a couple of new books have found their way into my possession. Otherwise, I would soon run out of quotes and anecdotes to bore people with. The first is Right Hand, Left Hand: The Origins of Asymmetry in Brains, Bodies, Atoms and Cultures, in which I expect to learn more about the superiority of left-handedness in all of the above. A quick leaf through reveals that even crystals can be chiral! No doubt the lefties are more stable. I love it.

Next up will be Science Friction: Where the Known Meets the Unknown, by Skeptic editor Michael Shermer. This one also promises to be a doozy, kicking it off with the following gem of an opener:

"It is in the vacuum of such will-nilly whencing and withering that we humans are so prone to grasp for transcendent interconnectedness. As pattern-seeking primates we scan the random points of light in the night sky of our lives and connect the dots to form constellations of meaning. Sometimes the patterns are real, sometimes, not. Who can tell?"

So many ideas, so little time. I'll go so far as to recommend both before even reading them. Or, check back at the bayblab for periodic updates and (what I think) are the coolest memes therein.

One last bonus - since I find myself reviewing the arts - I have to recommend Feist for great music to write or read to. Funky enough to stave off depression and keep you alert, soft enough not to be distracting. I've been checking out "Let it Die" and "The Reminder", and there's not a non-kick-ass track to be found on either. Big up to Amherst, Nova Scotia. Maybe she'll sit in with the spineless Kevin-Z one of these days. Hey, I could see it...

Bayblab Podcast Episode 13

One year anniversary podcast: supersize edition (twice the length, half the content). Discussions of the appendix, the Ignobel, the cancer carnival, and the usual beer-fueled nonsense.

James Dewey Watson Quote of the Week

"I don't think we're for anything, we're just products of evolution. You can say 'Gee, your life must be pretty bleak if you don't think there's a purpose' but I'm anticipating a good lunch."

- from a BBC interview with Richard Dawkins

Bay recipes: Marrow Rum

As we await the results of the Bayblab Pumpkin Brewing Project [(BP)²], I thought I'd share a recent discovery I made at the annual Ottawa Wine and Food Show. By discovery, I don't mean something I actually found and tasted, but a drink that came out of discussions with another (inebriated?) show patron. That drink is marrow rum.

The method is simple: cut the stalk off a fresh marrow (a marrow is a squash, similar to a large zucchini) and scoop out the seeds leaving as much flesh behind as possible. Pack the resulting opening with sugar (most recipes use Demerara - or raw cane - sugar). Replace the top, puncture the bottom and suspend over a bowl or some other receptacle. Most recipes I've seen depend on natural yeasts entering the marrow and fermenting the fruit, but I suspect adding yeast may be required. Some call for the addition of chopped ginger or raisins to add flavour. Fermentation time seems to range from a week up to several months, depending on the recipe!

A sample recipe:

Large marrow
Demerara sugar
Ginger
Pair ladies' nylon stockings

Slice the top off the marrow and scoop out the seeds, but leave as much of the flesh as possible, and don't puncture the skin. The seeds are attached to the inside of the marrow with little strings: one way to detach obstinate seeds is to fill the marrow with water and shake well. Fit a stocking onto the marrow, and pack the marrow tightly with Demerara sugar. Stand upright in a large vase or similar and leave for a day. Osmosis will draw fluid from the marrow into the sugar, dissolving some and leaving a gap below the end of the marrow. Add a teaspoon of ginger (finely chopped fresh ginger root if available, otherwise dried ginger) and pack more sugar on top. Replace the marrow upright in the pot, and cover to ensure nothing can fall into the pot or the end of the marrow. Pulling the second stocking down over the top of the marrow and pot is a good way to do this. Leave in a cool dark place for at least two weeks, and if possible, four. Inspect at intervals.

The idea is that the sugar ferments, generating an alcoholic liquor which gradually eats its way through the bottom of the marrow and collects in the pot. It takes three or four weeks to reach full strength, during which time the marrow becomes very floppy. The stocking filters the liquor and also provides much-needed surgical support. I have tried this recipe three times, twice with marrows and once with a Turk's Head Turban gourd, also from Elder Stubbs. One week's fermentation gives a liquor which has a pleasant taste but is not very strong - after three weeks, it has a noticeable punch. The ginger adds pungency to counteract the blandness of the marrow, giving the rum a pleasant warmth.

Whether the ensuing brew is a tasty potable, or instead something worthy of its British cooking heritage is unclear but it seems like a good candidate for the next bayblab project. Perhaps other fruit would make good candidates for recipe adaptations.

TH-sea

When I was in Japan recently I had the chance to try sea urchin sushi, which were delicious if you don't mind the texture. I hadn't eaten sea urchin since being a kid, when we used to collect them from the local beach in Spain and eat them fresh out of the sea with a dash of lemon. Now I was amused to find out in this article that sea urchin ovaries (the part you eat), has non trivial amounts of anandamide. Anandamide, which is derived from the word bliss in Sanskrit, is the endogenous canabinoid our body secretes. This may explain why some biologists waste their time with invertebrate zoology. More interestingly, the company described in the articles is trying to develop a THC - anadamide hybrid mollecule that would be even more potent against pain.

When thinking about it a little more it didn't surprise me that reproductive organs would contain the ligand, since they are known to express the receptors:

"With respect to reproductive organs, cannabinoid receptors and/or endocannabinoids have been detected in the pituitary gland, testis, Leydig cells, epididymis, prostate, sperm cells, ovary, uterus, oviduct, preimplantation embryo, placenta, embryo, fetus and neonates"

It is thought that in sperm, the anandamide prevents the acrosome reaction, therefore preventing the sperm from activating before it reaches the female tract and also preventing polyspermy during fertilization. The question is, how much anadamide (AEA) is there in reproductive biological fluids?




"We detected AEA, OEA, and PEA in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by HPLC/MS"

And the sequela, how much of that stuff do you need to feel a buzz?

"Oral administration of AEA and 2-AG to mice can produce psychotropic effects, suggesting that these endocannabinoids reach the brain ( Di Marzo et al., 1998)."

A quick survey of the literature suggest that 5.8mg/kg is the ED50 of AEA to impair working memory performance (i.e. get a mouse high). So a rough approximation of the dose of milk for an infant to feel the effects is 20,209 L of milk, or for a woman to get high of seminal fluid she would need to chug a good 62,142 L. Notice that calculating the converse would be morally reprehensible.

I suppose the fact that it's so dilute is a good thing for the baby since: "Newborn humans, that had been exposed to marijuana prenatally, exhibit increased tremors, exaggerated responses to stimulation, and spend less time sleeping quietly ( Fried and Smith, 2001).".... but it fails to explain why babies have such munchies...