Viral Catapults

It's been quite some time since I've written any posts here (not exactly true, I have about a dozen unfinished drafts of posts that I may get around to finishing eventually), so I thought I'd break the silence with the details of some interesting research on viruses recently published in Science¹.

How viruses spread and infect new cells within the body is just as important as learning how viruses are spread from person to person (or from other animals to humans, as the case may be). There are lots of ways viruses can spread to new cells once a host has become infected, and some of them are pretty interesting. Some viruses churn out massive amounts of viral particles and cause the host cell to rupture, and the swarms of progeny will infect nearby healthy cells. A team of researchers in the UK, however, have discovered a new method of viral cell to cell transmission that's a bit...different: viral catapults.

The team from Imperial College London, lead by Geoffery Smith, fluorescently tagged vaccinia poxvirus and using live-imaging techniques, were able to visualize how vaccinia is able to move from cell to cell. What they found is pretty interesting.

Once a cell has been infected by vaccinia, the virus hijacks the cell's replication machinery and uses it to rapidly produce massive amounts of two particular viral proteins called A33 and A36. These two proteins are then transported to the cell's membrane and are expressed on the outer surface, forming a sort of mesh around the cell. This mesh acts kind of like a tag that tags the cell as having been infected. When another vaccinia virus comes along and contacts the cell, it isn't able to get inside because of the A33/A36 complex. Instead, the virus gets lodged in the mesh.

Now for the really cool part. Once the virus has become lodged in the protein complex, this triggers a cascade within the host cell that rearranges its actin microfillaments (microfillaments, composed of action, are a part of the cell's cytoskeleton, the network of fibers that allows cells to maintain their shape and structure, as well as playing a role in cellular locomotion, division and intracellular transportation). The fillaments are rearranged into one long fillament that protrudes out at the site of viral attachment and sends the virus flying off into the intercellular medium, hopefully to find an uninfected host cell far away from the site of infection. Think of it kinda like hitting a billiard ball with a cue and knocking it to the other end of the pool table.

Totally cool.

This explains some observations made by Smith and colleagues about the rate of infection of the vaccinia virus. Vaccinia is seemingly able to move through populations of cells at a faster rate than would be predicted by viral reproduction rates alone (they were able to film a short video of the virus spreading quickly through a culture of cells, too! It certainly does move fast.) This ability of vaccinia to catapult itself to new potential hosts provides an adequate explanation.

Smith and co. went even further with their research. They knocked out the genes for A33 and A36 from the virus and found that these mutant viruses had significantly increased infection times. Furthermore, they inserted the A33 and A36 genes into healthy human cells, and found that it was sufficient to induce the virus-flinging reaction. This suggests that the whole mechanism - reception of the viral docking into the complex, signaling to trigger the rearrangement of the actin filaments and recruitment of the filaments to the proper location - is mediated by only two proteins! The team is not sure how the two proteins are able to pull off this task, but I'll be keeping my eye out for more research from their lab to find out.

---------------------------------------------------------------
1. Doceul, V., Hollinshead, M., van der Linden, L. & Smith, G. L. Science advance online publication doi:10.1126/science.1183173 (2010).

A.C. Grayling Knows This Much

AC Grayling is perhaps one of the better known philosophers of today, and he recently wrote a piece for The Guardian entitled "This Much I Know", filled with interesting philosophical tidbits. Here are a couple that I found the most poignant.

Science is the outcome of being prepared to live without certainty and therefore a mark of maturity. It embraces doubt and loose ends.

The democracy of blogging and tweeting is absolutely terrific in one way. It is also the most effective producer of rubbish and insult and falsehood we have yet invented.

A human lifespan is less than a thousand months long. You need to make some time to think how to live it.

I'm not sure it is possible to think too much. You don't refresh your mind by partying in Ibiza.

Fox News needs a lesson in geography...

Fox News might be the self-proclaimed "Fair and Balanced" (yeah right) news channel but it would seem they spent too much time mopping up Bill O'Riley's vile spew and not enough time reading their geography text books.



Notice anything a little off here?

I ask: how can anyone find Fox News a trustworthy source for information pretaining to issues in the Middle East when they don't even know the correct location of Egypt?

(via Media Matters)

The Food Network caves to Big Prayer™

The Food Network is not a television station that I watch alot (mainly because it makes me very hungry whenever I do), but earlier today I was watching a show about using liquid nitrogen in the kitchen. During one of the commercial breaks, an ad caught my attention. It featured a man, on the street, lamenting about the world's economic situation (try as I might, I can't seem to find the ad on Youtube). What piqued my interest was that the man began saying how he began praying that things would get better...but it didn't seem that prayer made any difference. He went on to say how he was beginning to question if prayer actually did anything. "Alright," I said to myself, "an ad supporting critical thinking and rationality!" That's when the ad turned a different direction: the answer, the man said, was because he simply wasn't praying big enough.

The ad, it turns out, was for a book called Pray Big. There wasn't really any information about the book, but it gave a website to check out: praybig.ca. So I did.

Pray Big, sponsored by "Crossroad Christian Communications" (the folks responsible for spewing out 100 Huntley Street) is written by Will Davis Jr., a guy who resembles a wimpy Al Bundy. He likes to point out that his official title is Dr. Will Davis Jr., despite the fact that his CV consists of a BA in History from Baylor University and a Masters in divinity and a "doctorate in ministry", whatever the hell that is, from Southwestern Baptist Theological Seminary (try getting a PhD from a real University before calling yourself a doctor next time, Davis).

The website claims:

"Will Davis Jr. offers straightforward guidance on how you can pray with focus and confidence for big things, small details, other people and, yes, even yourself. He teaches you how to pray and includes one hundred pinpoint prayers based on the Bible."

Davis supposedly teaches the idea of "big, pinpoint prayers". In other words, he thinks that prayers work better if they are specific and for big things (ignoring the fact, of course, that prayer of any kind doesn't work at all). He claims that when people pray they typically "underask" for things from God. The problem with prayer, he says, is that people should ask for MORE.

To be honest, I'm not surprised by this at all. The whole idea of prayer is inherently a selfish one. Christians believe that God put humans on the planet for the sole purpose of worshiping him, and nevertheless, they expect that their God should give them whatever they demand, just as long as they put their hands together, close their eyes and whisper some words off into the aether. Davis simply takes the egotistic concept of prayer and stretches it to the next level: don't ask for wimpy things, ask for BIG things!

But the bigger issue here is: why is the Food Network airing ads for this Christian hogwash? They are a private company, so I suppose they are allowed to air whatever ads they wish, but what do you think the chances are of airing an ad supporting a secular or humanist view? What do you suppose their excuse would be rejecting such an ad?

BBC puts 'mediums' to the test: Surprise! They're hacks!

Psychic "mediums" are con artists. Most critically thinking individuals are readily aware of this fact, but a large portion of the general public seems unaware of this. Why else would Sylvia Brown be a frequent guest of Montel Williams (despite her being wrong, wrong, wrong on so many occasions)? Why else would John Edwards have had a popular day-time TV show?

In an attempt to inform the general public and help keep people from being swindled by these snake-oil salespeople, the BBC put three mediums up to the test. The result: they're all cheaters. Big surprise there. Video below:



They took three mediums to "The Chocolate Factory", a made up factory with a fictitious history which they published on an "official" website, as well as planting tidbits of info around the building (like a portrait of the fake original owner, complete with his name on a plaque). They then took the mediums through the building and asked them to "channel" the history of the factory.

They all were able to "divine" the fictional history of the factory. Funny how they could contact the ghost of a person who never even existed.

The reasonable explanation, of course, is that they had read the information of the website before hand. Nevertheless, they all presented the information as having come from a channeled spirit.

And, as usual, once they are told that the whole thing was made up, they attempted to make excuses: "Oh, I was just testing you", "oh, I was reading your thoughts instead", "oh I wasn't wearing my glasses when I standing in front of George Bull's portrait".

Typical.

Beer, Chemistry and Marketing, a violently exothermic reaction of the brain.

Television advertisements.

Some of them can be absolutely ingenious. Some of them can be incredibly annoying. And some of them can be unquestionably, mindbogglingly stupid. The latest marketing campaign for Miller Genuine Draft beer belongs to this last category.

You've probably seen the commercials. They portray someone in a tough situation where they are uncommonly open, and consequently resolve the situation to their benefit. This is complete with their marketing slogan: "Miller Genuine Draft is in a clear bottle because it has nothing to hide", showcasing their unique clear bottles. And it's those damn clear bottles that make this marketing campaign so stupid. It would seem that the folks at Miller forgot to hire a chemist or two for their marketing department, because beer is bottled in dark bottles for a reason.

One of the key ingredients in beer is hops. Hops contributes much to the flavour of beer, through a class of chemicals known as isohumulones. Isohumulones are in all types of beer, and are perfectly fine. They are not a problem by themselves. Problems can arise, however, because of another chemical found in beer: riboflavin.

Ribovlavin (better known as Vitamin B2) is found in all kinds of foods and beer is no exception. Unfortunately, riboflavin and isohumulones don't get along very well. Riboflavin tends to break down isohumulones, so having them both in beer can be problematic. Normally, this is not a big deal, though, because the chemical reaction whereby riboflavin degrades isohumulones requires a catalyst, and that catalyst is light. This is the reason why beer comes packaged in dark-coloured bottles. The dark colouration keeps out light, and prevents the isohumulones from breaking down.

Why is isohumulone degradation a bad thing? Well, when these chemicals are broken down by riboflavin, they form a compound called 3-methylbut-2-ene-1-thiol. This compound gives the beer a very, very bitter taste: the beer becomes spoiled (unless you happen to enjoy very bitter beer, I suppose). If this happens to beer, then it is often referred to as being "skunky". Little wonder why: 3-methylbut-2-ene-1-thiol is very similar to the compound used by skunks in their spray.

So beer that is bottled in clear bottles like Miller Genuine Draft (as well as Corona, and beers bottled in green bottles like Heineken) will end up spoiling and becoming very bitter much quicker than beers packaged in dark bottles.

So does Miller Genuine Draft really have nothing to hide? I think the fact that their beer contains skunk juice is something worthy of keeping hidden.

EDIT: It's been brought to my attention that Miller uses a strain of hops that contains a more light-stable form of isohumulone to prevent their beer from skunkifying when exposed to light. Nevertheless, the chemistry remains the same and is still interesting. Take note all you home brewmasters out there.

Sex Determination and Lizards

Sex determination is a pretty hot topic in molecular biology. Trying to elucidate the underlying mechanisms that determine whether a fetus is male or female has been a productive field. Many species rely on a hemizygous¹ method of sex determination, and we humans are no exception (but rather, we are the rule). Males are XY and females are XX, and this is the way it works in all mammals² (even in monotremes like the platypus, though monotremes go to the extreme and can have as many as ten sex chromosomes; a male platypus is XYXYXYXYXY, for instance). Birds rely on a similar ZW system, but in this case, the females are heterogametic; females are ZW and males are ZZ. Some insects use an entirely different system, the XO system, where there is only one sex chromosome - X - and females have two (XX) whereas makes only have one (XO)³.

Despite the system used to determine sex, all the above examples have something in common: they all rely on genotypic sex determination (GSD). In these cases, it is the sex chromosomes (the number, presence or absence) which determines the sex of the resulting fetus. GSD, however, is not the only mode of sex determination. External environmental factors may also influence sex determination. Crocodiles, for example, have no sex chromosomes whatsoever. It is the temperature of the eggs which determines the sex; eggs laid in a warm nest become male and those in a cooler nest become female. Environmental sex determination (ESD) and GSD are not mutually exclusive, of course, and it has been known that many species of reptiles rely on both GSD and ESD. The interaction between ESD and GSD in these species was not thought to be a complex one; eggs at moderate temperatures use GSD, but the sex-chromosome method is bypassed and a temperature-dependant method is used if the eggs are at more extreme temperatures.

A new paper in Current Biology, however, shows that things might not be so simple.

Rajkumar S. Radder, David A. Pike, Alexander E. Quinn, and Richard Shine looked at sex determination in the eggs of the lizard Bassiana duperreyi⁴. They were examining how temperature effected the sex of the hatchlings when they noticed a correlation between the size of the eggs and the resulting sex: those eggs that were larger had female hatchlings and the smaller eggs had male offspring.

Of course, a simple correlation like this does little to prove an actual relationship and may simply be coincidence. So Shine and colleagues decided to try adding or removing yolk from the eggs during their development. What they found was pretty astounding. When they added extra yolk to the eggs, the hatchlings came out female, even if the sex chromosomes had already determined the sex to be male. And those eggs that had yolk removed switched to male even when the sex chromosomes had been set to female. This finding would suggest that sex determination in B. duperreyi is determined by a complex interaction of a minimum of three factors: sex chromosomes, temperature and egg size.

This also suggests that sex determination in any species may not be as simple as once thought.

------------------------------------------------------------------------

1. Hemizygous may not be a term you learned in Genetics 101. Whereas homozygous and heterozygous refer to having one or two different alleles, respectively, hemizygous refers to having only one of a set of two chromosomes. Female humans have two X chromosomes (XX), whereas males are XY; they are hemizygous with respect to the X chromosome. You could also refer to females as homogametic and males as heterogametic.

2. To be more specific, sex determination in mammals relies on a gene called sry (Sex-determining Region Y) located on the Y-chromosome. The gene encodes for a transcription factor called TDF (testis determining factor). When TDF is expressed, it influences the undeveloped gonad to develop into testes instead of the default state of developing into ovaries. If the SRY region of the Y chromosome is deleted or mutated, then the resulting child will be phenotypically female but genotypically male. Likewise, a translocation of SRY onto an X chromosome can lead to children who are phenotypically male but genotypically female. Interestingly, TDF does not begin to work, and consequently sex is not determined, until after the nipples have developed, which is why men have nipples that are pointless (beyond giving purple nurples, of course).

3. One interesting downside of this system is that it can lead to bilateral hermaphroditism. It is possible for the X chromosome to form a "ring chromosome" where the ends of the chromosome fuse together to make a ring. This ring chromosome is easily lost during cell division. If an embryo begins as XX (female), and very early on in development (at the 4 cell stage, say) a ring chromosome is formed and lost in one cell, the embryo will become split right down the middle, one side being male and the other side being female. This is rare, but not uncommon, in Drosophlia. Such flies are called gynandromorphs.

4. Rajkumar S. Radder, David A. Pike, Alexander E. Quinn, and Richard Shine. Offspring Sex in a Lizard Depends on Egg Size. Current Biology, 2009; DOI: 10.1016/j.cub.2009.05.027

Move over Boy Scouts, make way for the O.O.T.S.S.O.E.R.A.A.A.P

That is, the Order of the Science Scouts of Exemplary Repute and Above Average Physique. If you do science, this is the organization to be part of! And just like the Boy Scouts, you earn badges (to show off on your website/blog/whatever - along with a brief explanation how/why you've earned each one) for doing awesome sciencey stuff!

Here are the one's I've earned:

The "talking science" badge: Required for all members. Assumes the recipient conducts himself/herself in such a manner as to talk science whenever he/she gets the chance. Not easily fazed by looks of disinterest from friends or the act of “zoning out” by well intentioned loved ones.

The "I Blog About Science" badge: In which the recipient maintains a blog where at least a quarter of the material is about science. Suffice to say, this does not include scientology. Don't know exactly what porportion of my blog is about science but it's definately more than 1/4.

The "I’m pretty confident around an open flame" badge: Recipients have demonstrated proficiency around open flames in laboratory settings. I regularly use a Bunsen burner without disasterous consequences.

The "Destroyer of Quackery" badge: In which the recipient never ever backs down from an argument that pits sound science over quackery.

The "Sexing Up Science" badge: In which the recipient has had experience with things such as selective breeding, crossing, mate selection, prokaryotic conjugation, fertility studies, STD related microbiology, and/or any other acceptable interpretation of the badge. I vowed never to breed Drosophlia

again but at least it got me this badge.

The "has frozen stuff just to see what happens" badge, levels 1-3: In which the recipient has frozen something in the freezer (I)/dry ice (II)/ liquid nitrogen (III) for the sake of scientific curiosity.

The "I’ve done science with no conceivable practical application" badge. Perhaps this should be known as the "basic research" badge.

The "I know what a tadpole is" badge: In which the recipient knows what a tadpole is. Basically, an easy way to get a badge that looks a little like the semen one above.

The "Cloner" badge: In which the recipient has cloned something or other. I've done more cloning than you can shake a stick at. A cloned stick, even.

The "totally digs highly exothermic reactions" badge. Because who doesn't enjoy a fanciful display of exothermic activity?

The "somewhat confused as to what scientific field I actually belong to" badge. I'm trained in genetics, but I do molecular biology in a biochemistry lab. You tell me what my field is.

The "Works With Acids" badge. Usually only HCl and acetic acid, but hey, DNA

is technically an acid too!

The "Non-explainer" badge (Level 1): Where the recipient can no longer explain what they do to their parents.

My take on accomodationism.

Lately the science blogosphere has been abuzz with discussion about accomodationism. It all started off with a piece by Jerry Coyne for New Republic on the subject, which has since stirred the pot and prompted Chris Mooney, Jason Rosenhouse, Ken Miller and P.Z. Myers to give their two cents on the issue (a chronological list of postings and replies [as of June 12th] can be found here). There is alot to read about accomodationism but it all revolves around one question: is there room in science for religion - that is, can science and religion get along, or are they diametrically opposed?

And if you ask me, no, they can't and yes, they are.

The simple reason why is because science deals with the observable, the empirical, the testable; while religion deals with the metaphysical, the unobservable, the untestable. To be a scientist requires, then, a certain mindset - one that forsakes reliance in the intangible and deals wholly with physical reality. For one to have this scientific mindset and still hold a belief in religion requires a measure of doublethink in the true Orwellian fashion.

Much of the accomidationism discussion has talked about Gould's Non-Overlapping Magisteria (NOMA). In his 1999 book, The Rock of Ages, Gould proposed that science and religion attempt to explain different aspects of life: science attempting to explain how the world works and religion attempting to explain how we should act. If kept separate, then, the two magisteria should never conflict with one another. Accomidationists tend to use NOMA to suggest how science and religion can co-exist: if people keep them separate then there should be no problem with believing in both. Unfortunately, there is a big problem with using NOMA to justify accomodationism: the two magisteria DO NOT stay separate. Religion constantly makes an attempt to explain how the world works - take creationism for an example. Religion makes many claims about the physical world, which is supposedly science's realm. And many times, what religion claims and what science posits conflicts. To believe BOTH means you have to twist one to fit the other - usually twisting religion to fit science. The usual way is to claim that certain Biblical statements are just "symbolism". This poses a question: how do you decide which aspects to take "for real", and which are just "symbolism" (the answer is, of course, there is no criteria for deciding this). And if ANY of the Bible is symbolic, then what reason do you have to believe that any of it is real?

But there lies a bigger problem with accepting NOMA as a basis for accomodationism. If one is able to keep the magisteria separate, the very fact that one accepts the religious magisterium means that one accepts the idea that there are intangible, untestable entities and processes in existence. As a scientist, how could you ever divorce that idea from explaining the observable world? What keeps you from invoking the metaphysical to explain the physical? Again, there is no defined criteria for this judgement. One is resigned to proposing that there might be some unknown, intangible - in other words, unscientific - entity/process behind the physical world. And at that point, one ceases to be a proper scientist.

Now, I want feel I should say that this does not mean you cannot be a good scientist and be religious, or that being religious necessarily makes one a bad scientist. What matters is whether or not you incorporate your religious beliefs into your scientific activities. Once you try mixing the two, you cross the line from "good scientist" to "poor scientist". This is what separates the Ken Millers from the Michael Behes; Miller, while openly Christian, leaves his religion out of his science, and Behe, also openly Christian, insists on mixing the two. The problem lies, as I said above, in that to do this requires a measure of doublethink. You have to ignore (or attempt to explain away) the areas where science and religion are in disagreement, and you have to use the metaphysical for religious purposes and the physical for the scientific despite having no clear reason why they should be kept separate in the first place.

No doubt the accomodationism debate will continue. One wonders if it will ever be settled.

Why Biorad is one of my favourite companies.

If their first video wasn't awesome enough, this one is:



I also think it's funny how they made a 70's-esque video about a technique that was not developed until the mid-80's (unless you coun't Kleppe's paper as describing PCR¹).

--------------------------------------------------------------------
1. Kleppe K, Ohtsuka E, Kleppe R, Molineux I, Khorana HG "Studies on polynucleotides. XCVI. Repair replications of short synthetic DNA's as catalyzed by DNA polymerases." J. Molec. Biol. vol. 56, pp. 341-61 (1971)