The Scientific Quarterly

TWO GUYS WITH CREATIVE FACIAL HAIR DISCUSS THE MERITS OF THE FEDERAL GOVERNMENT’S INVOLVEMENT IN THE TERRI SCHIAVO CASE

By Christopher Monks

Hey, bro.

Hey.

What’s up?

Not much. You?

Not much. Just had a burrito.

Cool.

Yeah.

Was it good?

Was what good?

The burrito.

Oh, right. Yeah, it was.

Cool.

Yep.

What kind burrito was it?

Veggie.

Cool.

Yeah, it was a pretty cool burrito, bro.

Where’d you get it?

Get what?

The burrito.

Oh, right. I got it at Gary’s party.

Gary had a party?

Yep. It just ended. Was a blast.

I didn’t hear anything about it.

You didn’t?

No.

Hmm. I was wondering why you weren’t there.

Why didn’t Gary invite me?

Oh, I’m sure he meant to invite you.

?

Probably.

What kind of party was it?

Oh, it was a cool party, bro. Gary called it a “Feeding Tube” party.

A “Feeding Tube” party?

Yep. It was awesome.

What does that mean?

What does what mean?

“Feeding Tube” party.

Oh, right. Well, you see Gary knows this guy who’s a doctor, or maybe he’s a nurse — I forget — doesn’t matter, anyway, he brought, like, all this medical stuff from his hospital and we all got feeding tubes planted in our stomachs.

You all had feeding tubes planted in your stomachs?

Yep. Still got mine. Take a look.

[Looks at feeding tube]

Pretty sweet, huh?

Yeah, it’s kind of sore right now, actually, but whatever.

You ate your veggie burrito through a feeding tube?

You know it, bro!

?

That was like the best “Feeding Tube” party I’ve ever been to.

[Knock-Knock]

Hey, bros!

Gary! My man!

Hi, Gary.

Do I know how to host a “Feeding Tube” party or do I know how to host a “Feeding Tube” party?

Bro, you are the King of “Feeding Tube” parties!

No lie, bro!

I think my invitation got lost. Sorry I couldn’t make it, Gary.

What do you mean?

Well, there must have been a mix-up because I never got an invitation to your “Feeding Tube” party.

Oh, don’t worry about it.

Okay. Cool.

You didn’t get one because I didn’t invite you.

‘Kay, bros, gotta run. Gary out!

Later, Gary!

Man, that Gary is awesome.

Why didn’t he invite me?

Invite you to what?

His “Feeding Tube” party.

Oh, right. Don’t know. You make him mad or something?

I don’t think so.

I bet he was just pulling your chain, bro.

You think?

Yep. Definitely. That Gary is a prankster.

Maybe so.

[Knock-knock]

I’m back, bros!

Gary, baby!

Forgot my gun.

Oh, yeah, it’s over there on the coffee table.

Sweet.

That was a pretty funny prank you pulled on me, Gary.

What do you mean?

Well, when you said you didn’t invite me to your “Feeding Tube” party.

Prank?

Yeah.

?

Okay, guys! Gotta split. Gary out!

Later, Gar!

Gary is the man.

So my feeding tube is starting to itch.

Take it out then.

Is it supposed to itch?

I don’t know. Just take it out.

I’m afraid to.

Oh, for godssakes. Let me do it then.

Okay.

[Grabs feeding tube]

Be gentle, bro.

[Pulls on feeding tube]

Ow!

There. It’s out.

What’s out?

The feeding tube. [Flings feeding tube on the coffee table]

Oh, right. Thanks, bro.

No problem.

Wanna go get a burrito?

Okay.

Cool.

(Images from here).

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Christopher Monks once got a B on a biology quiz. He also wrote a book, "The Ultimate Game Guide to Your Life." In stores November, 2008. For more information please go here.

BREAKTHROUGH BREAKDOWN

By Jeffrey Roy Helm


(graphic altered from Kadivar et al., 2006)

If it’s not new, you can’t publish it; it is an axiom that illustrates a sickness in science. Doing biological research is not cheap, it takes time and money, and there is not enough of either to go around for everyone to fulfil their Nobel Prize dreams. If a scientist wants stability and adequate funding, i.e. a career, they have to produce. But these days knowledge is not enough; it has to be something that can turn into a “breakthrough”, a patent, or a pill. The pressure to produce, and for experiments to “work” can be enormous. Scientists can break under that pressure, having worked in many different research labs I have seen it happen. Although it may come as a surprise to some, scientists are only human.

Obviously Dr. Hwang Woo-Suk is only human as well, despite the initial fervent belief of his entire country that he was something more. Dr. Hwang Woo-Suk was made a molecular biology superstar when he published a paper in Science back in 2004 that described the first successful cloning of embryonic stem cells. The discovery, if true, would have given medicine a powerful new tool to treat spinal injury, neurological disease, and even cancer. But he faked all the results. Consequently the once drab orderly world of science got some drama and the papers have delighted in portraying a science community shocked by Hwang’s betrayal.

I have seen scientific ideals get quashed for the sake of a “positive result”. A whole career can be dependant on whether a drug makes a line on a computer screen go down. In that situation, when the line started edging down on its own, I heard a senior scientist say “quick, put on the drug now before it goes down more”. This is the true scandal that the Hwang fraud has uncovered, a cut-throat competitive climate where fundamental principles of science are disregarded in favour of getting a breakthrough.

A New York Times article quoted a researcher from Stanford that went off the same research track because it looked like Dr. Hwang had “made the process so efficient.” In the same article, a biotechnology company that was also doing similar research shut down when “the company’s financing dried up after Dr. Hwang claimed success.”

When a competing scientist has got everything apparently figured out and presented in a nice little package as Hwang did, other scientists get off the same research. This is often because they can’t get any funding for the project since the companies and agencies that hold the money bags tend to have a narrow view that one publication is enough “proof”. Even though scientific reasoning would say that once is never enough to prove anything.

A publication can provide a compelling argument for a theory but it doesn’t hold water until other scientists replicate the results. Any scientist worth their salt is a sceptic; there is no truth, only theory. If no one is able to replicate a scientist’s data the death of their career is just as certain, if not as dramatic, as Hwang’s. Hwang broke under pressure, he couldn’t have been thinking straight because every scientist knows that fraud will be found…eventually. You might be able to fool funding agencies, but you cannot fool the scientific community for long. Any well grounded scientist understands this fundamental concept that keeps science honest. So how did Dr. Hwang loose sight of this and commit fraud when he should have known that he would be found out eventually?

The larger issue at the core of this scandal has to do with what academic scientific research has become, a business in search of the positive result, the patent, and the pill that will secure a scientist’s future. Should we all be surprised that Hwang succumbed to dreams of fame and fortune? Or should we be more surprised that there are not more cases of fraud in science?

One publication puts out a model for scientists to test, but these days no one is getting any money to test anything. If a lab does get the luxury to investigate another scientist’s work it has to couch it with a new twist before it can publish and get the information out. The current economics of science is the true scandal in the Hwang fraud. Labs only get money for the breakthrough and science journals only want to print the breakthrough. So what or who is going to make sure the breakthrough is real?

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Jeffrey is an ex-scientist turned science writer. Right now he's in the Journalism program at UBC and trying to be a writer...or at least get better at writing. Apart from science writing he also dabbles in the Rock and does pieces for Discorder.

CHILD’S PLAY

By Kara Stanley

My brother sent me a subscription to the British magazine New Scientist last Christmas. I love it. It arrives once a week and sits, like a center piece, in the middle of the kitchen table. Everyone in the family takes turns reading it, each finding, at different times during the week—over coffee and toast, before soccer practice, while the spaghetti sauce simmers—bits of articles that are so awesome we are compelled to read them aloud to one another.

Oh my god, one of us will say, you have to hear this.

Over the past year conversations at the kitchen table have included the plight of the very versatile, yet genetically challenged banana; the implications of the epaulette shark’s ability to rise, like Lazarus, seemingly from death; the possible global value of jojoba oil, and, most spectacularly, a phantom menace that has the potential, as the headline read, to rip the cosmos apart. I collected this particular issue from my mailbox the week before U.S and British forces declared war on Iraq. It turns out that in the month prior to the war, as thousands around the world demonstrated, physicists were grappling with revolutionary new information. The first results of the Microwave Anisotropy Probe (MAP) were released and its potential implications were, well, explosive.

Stand by for a nightmare end to the Universe—the article began—a runaway expansion so violent that galaxies, planets and even atomic nuclei are literally ripped apart.

* * *

The initial profile of our universe, according to MAP, looks like this :

Age: 13.7 billion years (or roughly 3 times the age of the earth)

Age when first light appeared: 200 million years ago

Contents:
4% ordinary matter
23%dark matter, nature unknown
73% dark energy, nature unknown

Hubble constant (the expansion rate of the universe):
71km/sec/megaparsec

Shape: flat

* * *

My partner Simon and I became avid Star Trek watchers during the time I was pregnant with our son. After dinner, we snuggled up in a big wicker chair, a spot just big enough for both of us and my belly, and turned on the TV. Space, the intro began, the final frontier. Simon would speak along with the resonant voice of Jean Luc Picard. Space, he’d say, bigger than a breadbox. I enjoyed the show but my favourite part was always Simon’s improvised over-dub.

Space……bigger than the gap in your little sister’s two front teeth.

Space….right after spa in the dictionary

Sometimes he leaned towards my tummy, my extroverted belly button acting as a kind of microphone.

Space…he’d say, loud enough for unborn Eli to hear, it lacks a reliable transit system.

* * *

The fourth member of our household, a goofy black dog, was named by Eli. We were reading Madeleine L’Engle’s novel A Swiftly Tilting Planet, which takes place over a Thanksgiving weekend. During dinner the family receives a phone call from the President informing them that the world is under dire threat. A mad dictator from an obscure nation is threatening to deploy nuclear weapons. The main characters use time travel and mental telepathy to alter the fabric of history and, in doing so, avert the global catastrophe. They are helped in their mission by a stray dog who appears unexpectedly during the long dark night. They call her Ananda.

“It’s Sanskrit,” Charles Wallace explains, “[meaning the] joy in existence without which the universe will fall apart and collapse.”

“When we get our puppy,” Eli interrupted my reading, “I want to call her Ananda.”

Ananda was born on September 10th 2001, a date which has always been significant to Eli.

“It’s a hopeful thing,” he says.

* * *

Much of what I read in New Scientist I don’t really understand. For example, I don’t know how to understand that space is flat. It seems incomprehensibly strange and I feel what it must have been like, in times long past, to newly learn the earth was round. But….but…but.., I stutter, the universe may be flat but it is not just flat. Not if there are wormholes, and parallel or alternate universes, not if existence is multi-dimensional, time non-linear. Wormholes, parallel universes, an eternally present moment—to some degree these are fantastical concepts I can entertain, at least metaphorically, if not through an equation or a geometric diagram. But…flat? I’m not sure what to do with a thought like that.

I open the pages of my rather thin magazine and suddenly I am transported, a child who has been told to go outside and play. I step into a back yard that has been un-fenced and the world unfolds around me, vast and messy: flat, peaked, blobbed, swirled, swollen, bubbled, pocketed. Unimaginably large. Unimaginably unimaginable.

I did not enjoy feeling like a child the week that U.S and British troops moved into Iraq, but it was a feeling I couldn’t shake. It tailed me through town, as I filled my car with gas, as I picked up bulk bags of all-natural lamb, rice and veggie dry dog food, when I stopped at the grocery store to pick up ice cream. The week before I had experimented with a ‘compound’ flavour of ice cream and it had caused ripples, and not the good, butterscotchy kind.

“Bring home some vanilla ice cream,” Simon had said. “Make me feel like I have a home again.” After securing two litres of Breyers All Natural Light Vanilla I somehow managed to fill my cart with things I didn’t even know I needed: 4 packages of Minute Maid orange juice drinking boxes (on special), a pineapple (also on special), peanut butter (you can never have too many jars). And more: fold-over sandwich bags, Dad’s chocolate chip cookies, pre-made hummus, a box of instant oatmeal. Standing in line, staring at my full basket of questionable necessities, I felt kind of sick. Spoiled. “The war on Iraq,” a TV news item from the night before had begun, “wages war on American waistlines.” People, suffering from war time anxiety, were soothing their stress with excessive amounts of fast food. Ahead of me in line, two guys, around my age, talked in excited, drippy tones about the latest U.S military gear.

“I know it’s not cool,” one said, “but, fuck, watching the fighting at Umm Qasr was like watching the best video game ever.”

At home I abandoned my groceries and wandered into my overgrown garden. In the car, the ice cream melted. I was distracted by the witch hazel. It had been a damp, gray winter and this bright yellow bloom was an unexpected gift. In and out of the fringed petals flitted a hummingbird, the first of the season. It was a sharp sliver of brown, this hummingbird, a tiny racing heart with wings. I sat by the witch hazel a long time watching the buzz and blur of colour come and go. I was tired of not knowing what to do. I wanted to grow-up.

* * *

It is forgivable that, in the aftermath of MAP’s findings, scientists were either a little shrill, or totally silent. MAP confirmed some of the most speculative of speculations. Designed to measure the cosmic microwave background, MAP now provides a clear record of the history of our universe. The way I understand it, it’s kind of like carbon dating a dinosaur bone, but on a lot bigger scale.

Scientists have known for roughly the past 70 years that the universe appears to be expanding, but, with a kind of arrogant anthropomorphism, it was assumed that, like human life, the expansion rate would eventually peter out. MAP findings suggest otherwise. Still, it seems to me that sensational concern over increased expansion is kind of a misplaced anxiety, a galactic red herring. (I mean, c’mon guys, why get your panties in a twist over a “Big Rip” scenario that could play out as soon as 22 billion years from now.) No, the thing that is really upsetting the physicists, as far as I can figure, is that after all their theories—general, special, quantum, string—it turns out that only 4% of the universe is know-able, ordinary matter. Only 4% is the stuff that makes up planets and super novas, car keys, milk-shakes, beaks, bones, tidal waves, meteors and moth wings. The rest—96%—is a mystery.

* * *

I didn’t know what to do. What do you do when you feel something to be so profoundly wrong and yet you have so little power to affect it? What do you do when morality and reason flat-lines at the highest levels of power and influence?

In January 2000 George W Bush stood before an audience at the Iowa Western Community college and, in language that eerily pre-dated the rhetorical flourishes of the War on Terror, had this to say:

When I was coming up, it was a dangerous world and we knew exactly who they were. It was us versus them and it was clear who them was. Today, we are not sure who they are. But we know they’re there.

This was not the speech of a studied and thoughtful politician. This, to me, was Big Brother engaging in some horrific form of child’s play. Could the devastation that war entails really be as arbitrary, as entertaining, as the ultimate millennial game of cops and robbers? The definitive cinematic version of cowboys and Indians? The best fucking video game? And if that idea scares you, or sickens you, what do you do? What do you do with thoughts like these?

I didn’t know what to do but to start with the details: small, banal, daily, domestic, personal. So. The next week I bought a bulk bag of organic oatmeal and woke up fifteen minutes earlier to make it for breakfast. I called my best childhood friend and told her I loved her and that I didn’t want to maintain my side of the argument—old as brothers and sisters—that lay between us. I took a day off to take Eli to a track and field meet. Afterwards, instead of rushing back to work, we bought milkshakes and went to the beach. I read a story out loud from the New Scientist about the discovery of a star called HE0107-5240I which, at 13.5 billion years old, shared its infancy with the universe. I tried to be a better, less distracted parent. Simon and I had long discussions about how compelling the phrase ‘you’ll do it because I told you so’ was when parenting a pre-pubescent boy. We talked strategies; we talked conflict-resolution. I avoided TV and newspapers because it was there, through daily repetition, that the unthinkable was being transformed into the acceptably normal. I visited ZNET (The Spirit of Resistance Lives) for Iraqi conflict updates. I kept a journal of information I could reliably consider facts:

March 29th Cluster bombs explode, biblical in their wrath, and scatter bomblets over a wide radius. The sky rains grenades. A single cluster bomb saturates an area the size of football field with sharp, flying steel. At least 5% of the bomblets, often far more, don’t explode, but live on as landmines. Human Rights Watch says that approximately 4,000 civilians were killed by unexploded cluster bomblets after the ’91 Gulf War. Presently, deaths and injuries sustained by children from unexploded cluster bombs are approximated to be around a 1000 a month.

Baby steps. I felt as if I had reached some kind of developmental plateau, one defined by my own limitations, my own irrelevance. It was hard, and it hurt, to read or see or think too much on the subject. And it wasn’t just me. People were soon tired of talking about it. Conversations aggressively veered away from the topic. It wasn’t cool to belabour the point. “NBC moves War”, began a satirical headline in the online magazine The Onion, “to Thursday, after Friends.” No weapons of mass destruction were found. The language of war, rife with bulky, over-fed acronyms, split its seams. Semantic distinctions blurred in translation. A ‘defensive line’ was both defensive and offensive, depending on which side of the line you stood. A liberator looked an awful lot like an invader, depending on which side of the line you stood. Friendly fire was not friendly at all. The predictably disastrous side effects of war upon an already devastated country’s infrastructure and ecology occurred, continued to occur. May 1st came and went. The war was over but, like the over 300 000 rounds of uranium shells leaching into the soil and water of the Iraqi landscape, I found the ideas it generated, whether we talked about them or not, still continued to sicken.

* * *

Alongside my journal entries I compulsively collected the articles in the New Scientist that pertained to dark matter and dark energy. It was perversely gratifying to see how these unknown forces seemed to echo, on a cosmic level, both current U.S foreign policies and, more generally, the aims of all terrorist activity. The fact that the U.S represents 4% of the world’s population—the same percentage of mass that constitutes the knowable universe—seemed to be a coincidence pregnant with possibility, albeit possibilities I could never logically unravel. The physicist’s initial choice of nomenclature, (cold dark matter, repulsive dark energy), with all its social and metaphorical baggage, translated, at the time, into a literal representation of how I felt. Small and insignificant. Helpless against larger and unknown forces.

* * *

Often, I miss the ecstatic and anarchic despair of my adolescence, (soundtrack by Peggy Lee and Patti Smith, and a little Neil Young, for when the boys came around). Then, my anger and confusion had been visceral and immediate, uncompromising. Stylistically pleasing. I would never have worn track pants out the door, nor Gore-Tex. There had been both tragic glamour and scrappy indifference in the act of lighting a cigarette. I always wore funky, revolutionary shoes.

I find myself cringing a little at the wholesome earnestness of my ‘mature’ personal solutions to global crisis: oatmeal recipes and parenting tips, quotes that run along the predictable lines of ‘seize the day’ or ‘take nothing for granted’.

But… I can no longer do apocalyptic joy any more than I can sleep in until two in the afternoon. I have a child. And as often as I feel like a kid (bewildered, bumfuzzled, lost at the mall), I am also a parent.

Spring dressed itself up into summer. In our front yard the cherry tree bloomed, the fruit ripened. It was a hot summer and the cherries ripened quickly, faster than we could pick them, and the fruit fermented in the uppermost branches. The birds congregated like college students and threw an all-day and all-night party, their cries becoming more lucid and slippery. Eli and I left shallow dishes of water, (not deep enough to pass out and drown in), around the yard so the soused birds didn’t dehydrate. Ananda kept an eye out for cats on the prowl.

* * *

After a while the headlines became less shrill. The scientists started outlining the details they could reliably consider to be facts. Cold dark matter, aka WIMPs (Weakly Interacting Massive Particles), or 23% of the universe, has proven, to the physicists who would like to ascribe singular and consistent characteristics, remarkably unpredictable. What is known of the nature of repulsive dark energy, aka the cosmological constant, or 73% of the universe, is paradoxical: the cosmological constant would appear to be the property of nothingness, the energy of empty space. The fact that a cosmological constant has now been proven to exist stands as a challenge to hundreds of years of thought about the ‘fixed’ laws of nature. Our entire paradigm of human life—and its place in space—needs to be re-thought.

The details of our universe just got a whole lot messier. Messy, I’d like to think, in the good way that kitchens can be. If our natural laws aren’t fixed, then, really, anything is possible. It seems we—parents, children, physicists, dictators—are all just playing in the dark. I imagine skipping through time and space like a kid playing hopscotch. I imagine travelling unexplored landscapes that, by their nature, resist narrow definitions and are immune to mandates of conquest and colonization.

These are ideas that make me feel infinitely happy.

* * *

A few weeks before Christmas, Ananda was killed by a hit-and-run driver. In the difficult days after her death I struggled with the superstitious thought that, without her, the three of us would somehow lack cohesion as a family. It was a trick of my mind, I knew, true and not true, a mental slight-of-hand playable only in a time of crisis.

It was my son’s first experience of loss and, as he moved through the different stages of saying good-bye, I made a conscious decision not to make this family tragedy relative. I made a conscious decision not to rank it on the great scale of earthly tragedy. I let it be. Grief rolled through our home like a tidal wave. And then, gradually, it receded.

* * *

(REPRINTED FROM ISSUE ONE, JUNE 20th, 2005)

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Kara Stanley is a graduate of UBC's MFA Creative Writing Program. She is currently hard at work finishing up her first novel gutbucket thunder. "Child's Play" originally appeared in Fugue.

RESURRECTING DAMAGED NEURONS: ARE WE FIGHTING A HOPELESS BATTLE?

By Melvin Kwok

Spinal cord injury (SCI) has been documented throughout history. Early physicians described patients with this affliction to be conscious and aware yet unable to innervate their limbs. Up to the mid 1960s the proper course of treatment for SCI was to stabilize the spinal cord to avoid further injury. Repair, however, was deemed impossible. It wasn’t until recent developments in molecular biology and biotechnology over the past decade that an understanding of the true molecular mechanisms behind SCI has been unraveled to provide a small glimpse of hope. To this day, there is not a cure for SCI but studies in biochemistry and genetics are starting to paint a clearer picture of the events that occur during SCI. With these insights comes the hope that there is a cure buried among the depths of this information. However, there exists some doubt as to whether a cure is really possible. Are scientists and physicians fighting a hopeless battle?


Figure 1: a diagram of a healthy spinal cord

Since the mid 1990s when the first neuronal chemical attractant was identified by Tessier-Lavigne and his group[1-3], numerous studies have identified chemicals that attract and repel growing neurons during development [4-6]. These chemical signals are important because they guide the developing neuron toward its target so that it can innervate specific neurons or muscle fibers. Among the chemicals and receptors being identified, there were some identified as responsible for destroying the path-finding portions of growing neurons known as the growth cone [4-8]. Growth cones are the sensing unit of the growing nerve cell that is designed to sense the surrounding environment in order to help make decisions about which direction to grow [9]. Immediately following SCI, injured nerves have demonstrated the ability to form new growth cones that explore the surrounding environment and try to make connections that have been lost due to the injury [10,11]. Figure 2 shows how a growth cone should function either during development or in the event of nerve damage. Why, then, are previous connections not reestablished?

Severed neurons have difficulty growing and finding their original targets because the environment surrounding these new growth cones is a hostile one [12,13]. The nerve and the surrounding area has sustained significant trauma. As a result, the insulating myelin sheath has usually been torn and there is inflammation of the surrounding area in response to the injury [14,15].

Secondary Damage
Inflammation under normal circumstances is a welcomed primary immune response to injury because the series of events: heat, swelling, redness and pain are all useful to the body [16]. It promotes the recruitment of macrophages and other immune cells [16]. Macrophages are responsible for the clearance of cellular debris, production of toxins to kill any foreign bacteria or viruses as well as the generation of chemicals that promote the healing process [16]. The spinal cord is usually an immune privileged site, which means that immune cells normally do not have access to this area. However, when SCI is sustained, the barrier that separates the nervous system from the rest of the body is damaged and macrophages gain access.

Under these circumstances, inflammation can do more damage than good because the toxins that macrophages create are deadly not only to bacteria and viruses, but to the cells of the nervous system as well. These toxins include reactive oxygen and nitrogen species that are capable of destroying proteins and damaging cellular membranes [12-15]. Also, macrophages will produce and secrete chemicals known as interleukins. Interleukins have the ability to trigger the activation of many intercellular signals by activating nuclear factor kappa B (NFkB)[16-18]. Active NFkB will lead to the transcription and activation of genes that cause cellular decay and programmed cell death, known as apoptosis, to occur. As a result, the normally positive actions of the immune cells turn out to have disastrous effects on the newly injured spinal cord, causing an effect known as “secondary damage” [12-15]. Through the actions of secondary damage, the initial mechanical damage done to the spinal cord and surrounding tissue is made worse by chemical damage due to inflammatory events [14]. Secondary damage will spread outwards from the point of injury killing damaged cells and, eventually, even healthy cells that are adjacent to the injured areas [14].

Growth Cone Collapse
Although the inflammatory response can make things worse, given enough time inflammation does dissipate, the reactive oxygen and nitrogen species are no longer created and the area is allowed to recover to a normal healthy state. Why, then, will the damaged neurons not send out new growth cones across the damaged area to reestablish previously severed connections?

When the nerve is damaged, the surrounding glia cells tend to up-regulate the production of chondroitin sulfate proteoglycans (CSPG)[19]. These proteins are normally responsible for facilitating interactions with cell adhesion molecules and growth factors necessary to maintain a healthy nervous system [19]. However, the over-production of CSPG causes the formation of a blockade that surrounds the broken nerve endings. This is known as the glial scar and has inhibitory effects towards axon regeneration [20]. Embedded in the glial scar are molecules that have been demonstrated in several lines of experiments to have repulsive effects on the growth cone [19,20].

Nogo protein was the first to be identified as having inhibitory effects towards newly developing growth cones [21]. It is a small transmembrane protein that is found on the inner-most layer of the myelin sheath [22]. This protein was identified by isolating protein fractions from rat brain myelin that displayed inhibitory effects on growing growth cones [22]. Through subsequent characterization, an extracellularly exposed region of 66 amino acids known as Nogo-66 was found to be responsible for the inhibitory effects of Nogo [23-25]. Myelin-associated glycoprotein (MAG), a protein initially implicated in the formation and maintenance of myelin sheaths was also identified to have inhibitory effects on neurite (cultured neuron) outgrowth [26,27]. MAG turns out to have dual roles of developmental significance: it can promote the outgrowth of immature neurons and inhibit the growth of mature neurons [28]. Finally, oligodendrocyte myelin glycoprotein (OMgp), a protein involved with the onset of myelination during the development of growing neurons was also identified to have neurite outgrowth inhibitory effects [29,30]. Nogo, MAG and OMgp together are responsible for the majority of the inhibitory effects observed at the site of injury [31].

Contrary to the conventional single ligand to single receptor model, all three of these proteins have strong affinity towards the same receptor known as the Nogo-66 receptor (NgR) [24,30,32]. The binding of just one of these inhibitory proteins to NgR on the newly developed growth cone is enough to cause the initiation of downstream events. Activated NgR has the ability to signal a downstream cascade. This cascade starts with the activation of Rho, one of the 3 main proteins responsible for actin remodeling within the cell [33-35]. Rho has the ability to down-regulate the effects of Rac and Cdc42, causing destabilization of actin filaments and leading ultimately to growth cone collapse [33,34,36]. Once the growth cone has collapsed, the growing nerve axon can no longer grow in that direction until a new growth cone is formed.

Fighting A Hopeless Battle?
Certainly, with the evidence presented it would seem that regenerating a severed spinal cord is an impossible dream. There are layers upon layers of complications that make it difficult for neurons to grow even if they wanted to. But why are there so many obstacles in place? If the regeneration of peripheral nerves from a cut at your finger tip is possible, why is it so difficult to regenerate damage sustained by the central nervous system? Although the answers still elude scientists, progress in molecular medicine has provided important insights. For example, pyrrolidine dithiocarbamate, an anti-inflammatory drug, when administered to rat models of SCI demonstrate that an attenuated inflammatory response following injury will limit the degree of secondary damage sustained [37]. In mice, stopping NgR from binding to its partners demonstrated partial functional recovery following experimental SCI [38]. Ongoing experiments are underway to identify the genetic determinants that are responsible for inhibiting the growth of recovering neurons. Researchers are looking into treatments such as gene therapy, synthetic nerve fibers, surgical grafting approaches and even the use of specialized electromagnetic fields to stimulate the regeneration of damaged nerves [39-42]. With more work and an even greater understanding of the mechanisms mentioned in this article, potential cures are just around the corner. The once impossible battle against spinal cord injury may not be so hopeless after all.

References
1. Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell. 1994 78(3):409-24.

2. Kennedy TE, Serafini T, de la Torre JR, Tessier-Lavigne M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell. 1994 78(3):425-35.

3. Colamarino SA, Tessier-Lavigne M. The role of the floor plate in axon guidance. Annu Rev Neurosci. 1995 18:497-529.

4. Garbe D, Bashaw G. Axon guidance at the midline: from mutants to mechanisms. Crit Rev Biochem Mol Biol. 2004 39(5-6):319-41.

5. Salie R, Niederkofler V, Arber S. Patterning molecules; multitasking in the nervous system. Neuron. 2005 45(2):189-92.

6. Hinck L. The versatile roles of “axon guidance” cues in tissue morphogenesis. Dev Cell. 2004 7(6):783-93. Review.

7. Barton WA, Himanen JP, Antipenko A, Nikolov DB. Structures of axon guidance molecules and their neuronal receptors. Adv Protein Chem. 2004 68:65-106.

8. Chotard C, Salecker I. Neurons and glia: team players in axon guidance. Trends Neurosci. 2004 (11):655-61.

9. Hippenmeyer S, Kramer I, Arber S. Control of neuronal phenotype: what targets tell the cell bodies. Trends Neurosci. 2004 27(8):482-8.

10. Martin KC. Local protein synthesis during axon guidance and synaptic plasticity. Curr Opin Neurobiol. 2004 14(3):305-10.

11. Ramesh V. Merlin and the ERM proteins in Schwann cells, neurons and growth cones. Nat Rev Neurosci. 2004 5(6):462-70.

12. Beattie MS, Farooqui AA, Bresnahan JC. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 2000 17(10):915-25.

13. Beattie MS, Li Q, Bresnahan JC. Cell death and plasticity after experimental spinal cord injury. Prog Brain Res. 2000 128:9-21.

14. Beattie MS. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med. 2004 10(12):580-3.

15. Kulkarni AP, Kellaway LA, Lahiri DK, Kotwal GJ. Neuroprotection from complement-mediated inflammatory damage. Ann N Y Acad Sci. 2004 1035:147-64.

16. Janeway, CA., Travers, P, Walport, M, Shlomchik, M. Immunobiology. 5th ed. New York and London: Garland Publishing; c2001.

17. Murakami Y, Shoji M, Hirata A, Tanaka S, Yokoe I, Fujisawa S. Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages. Arch Biochem Biophys. 2005 15;434(2):326-32.

18. Mukundan L, Bishop GA, Head KZ, Zhang L, Wahl LM, Suttles J. TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J Immunol. 2005 15;174(2):1081-90.

19. Matsui F, Oohira A. Proteoglycans and injury of the central nervous system. Congenit Anom (Kyoto). 2004 44(4):181-8.

20. Jain A, Brady-Kalnay SM, Bellamkonda RV. Modulation of Rho GTPase activity alleviates chondroitin sulfate proteoglycan-dependent inhibition of neurite extension. J Neurosci Res. 2004 77(2):299-307.

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22. Caroni P, Schwab ME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J. Cell Biol. 1988 106:1281-88

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29. Barton WA, Liu BP, Tzvetkova D, Jeffrey PD, Fournier AE, Sah D, Cate R, Strittmatter SM, Nikolov DB. Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins. EMBO J. 2003 22(13):3291-302.

30. Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He Z. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 2002 417(6892):941-4.

31. He Z, Koprivica V. The Nogo signaling pathway for regeneration block. Annu. Rev. Neurosci. 2004 27:341-68.

32. Liu BP, Fournier A, GrandPré T, Strittmatter SM. Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor. Science 2002 297:1190-93.

33. Dickson BJ. Rho GTPases in growth cone guidance. Curr. Opin. Neurobiol. 2001 11:103-10.

34. Ettienne-Manneville S, Hal A. Rho GTPases in cell biology. Nature 2002 420:629-35.

35. Luo L. Rho GTPases in neuronal morphogenesis. Nature Rev. Neurosci. 2000 1:173-80.

36. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998 279:509-14.

37. La Rosa G, Cardali S, Genovese T, Conti A, Di Paola R, La Torre D, Cacciola F, Cuzzocrea S. Inhibition of the nuclear factor-kappaB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats. J Neurosurg Spine. 2004 1(3):311-21.

38. Kim JE, Liu BP, Park JH, Strittmatter SM. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron. 2004 44(3):439-51.

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40. Tsai EC, Dalton PD, Shoichet MS, Tator CH. Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection. J Neurotrauma. 2004 21(6):789-804.

41. Itoh S, Matsuda A, Kobayashi H, Ichinose S, Shinomiya K, Tanaka J. Effects of a laminin peptide (YIGSR) immobilized on crab-tendon chitosan tubes on nerve regeneration. J Biomed Mater Res B Appl Biomater. 2005 7; [Epub ahead of print]

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(Images by Jane Philpot)

* * *

(REPRINTED FROM ISSUE ONE, JUNE 6th, 2005)

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We know Melvin Kwok is a graduate student at the Department of Pathology at UBC. Beyond that, we assume he was, perhaps, on holiday.

HEADS UP: RAMEN

By David Johnson

(In which we present this piece to acknowledge that a bevy of FSM contest pieces will soon be presented in the upcoming weeks. This, of course, includes the one that will win $100 worth of Ramen noodles)

- – -

In the beginning, there was nothing. What happened thereafter has come under great debate, until now. Recent archeological finds and the forefront of scientific discoveries have aligned to reveal to us that He created all. The Flying Spaghetti Monster is set apart from average deities and is certainly not your average flash-in-the-frying-pan David Koresh or Heaven’s Gate Doctrine. No, as the logical arguments that follow will prove, we all have been constructed in the image of His Noodly Appendage and our technology hinges upon gifts He revealed to us in His weaker moments.

The historical evidence of the Flying Spaghetti Monster abounds. Recently discovered noodles show just how far back we have been creating and eating mana from Him. The Chinese have uncovered a bowl of noodles four thousand years old. The Arabic peoples claim noodle consumption for three thousand years and the Europeans did not exist without noodles with which to whet their palettes. For it was believed, millennia ago that to make Him present required one of the most holiest of skills—boiling water. It was through this magical process of heating water that one could perform transubstantiation on grain-based dry noodles and produce His essence.

The mere fusion of meat with grain shows that He is Complete in knowing of all things and an expert in Carne Knowledge.

Indeed, unity is seen in the Flying Spaghetti Monster as all grains can take the holy shape of long life giving strands. Regardless of color, texture or heartiness, any grain can be used to produce the base of The Dish which permeates all of our souls. In this, we see that The Flying Spaghetti Monster has created all equally.

With recent research done in string theory, we can prove that we all have been constructed—on a very basic level—to look like Our Dish Most Holy. Super strings reveal to us the unifying and binding miracle of life that He has breathed into us. Every atom of our being is made of quarks which are in turn made of tiny strings vibrating towards spaghettidom. Popular physicists like Brian Greene have been chosen as the prophets of this new revelation. His message is clear! He is with us at the quantum level! This is the final noodly link between the electromagnetic and nuclear forces of science!

Gödel failed to account for spaghetti in his Incompleteness Theorem. Newton never dropped noodles on his head—had he done so he would have discovered they slide off and defy gravity. Einstein could never explain the amount of energy one gets from consuming hallowed spaghetti. This is why these brilliant men failed to recognize His Power. And I will close with evidence that He is with us even through poetry. The following ancient haiku reveals how revered The Flying Spaghetti Monster truly is:

Time is but a noodle
connected from end to end.
Forever turning.

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David Johnson has a bachelor of science in computer science from the University of Minnesota in the Twin Cities. He is now a graduate student at George Mason University in computer science. Between a full time job and school, he enjoys reading "Ulysses" by James Joyce obsessively. His outlets include playing bass, making light of serious things and whiskey.

A FABRICATED PAPER: MITOCHONDRIAL EVOLUTION: SHOULD I STAY OR SHOULD I GO?

By Jonathan Choy, Kenneth Liu, Catherine Tucker, Mitra Esfandirei, and Steven Quayle

(This paper was designed by a group of students for a class project, and as such is completely fabricated)


TITLE:
Mitochondrial Evolution: Should I stay or should I go?

ABSTRACT:
The distinction between prokaryotic and eukaryotic cell structure is still accepted today as the most fundamental discontinuity in the living world. In the process of analyzing the newly sequenced bacterium Rickettsia prowazekii it was discovered through a BLAST search that a non-coding region of DNA showed high homology to the importin-α gene of eukaryotes. The genomes of Rickettsia canada and Rickettsia rickettsii were both found to contain a sequence homologous to importin-α as well. This sequence was found to have high homology when compared to the primitive protists Nosema locustae and Reclinomonas americana, which close ancestors to the lineage. The predicted protein sequence of R. prowazekii, R. canada and R. rickettsii contained the highly conserved amino acid motif cys-arg-glu-ala-thr-glu-…-ser-glu-val-glu-asn-asp-ala-tyr-ser. We believe this motif may be specific to a new lineage of prokaryotes, which we have termed the Eukobacteria. Through the data collected we propose a new model of mitochondrial evolution wherein one or more mitochondria escaped from their eukaryotic hosts and developed into the Eukobacteria.

(download pdf of paper here)

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These students are real - pathology graduates actually.

HISTORY’S GREATEST MINDS TACKLE SCIENCE’S GREATEST UNSOLVED MYSTERIES

By Patrick Francis

Dark Matter

En route to Daphne’s uncle’s seaside cabin, Scooby Doo and the rest of the Mystery Inc. gang are waylaid at an abandoned amusement park – which, according to the kindly local innkeeper, is haunted by matter that cannot be detected from the light which it emits. So mysterious is this ‘dark matter’ that its presence can only be indirectly inferred from motions of astronomical objects. Unclear as to how this would constitute the type of adventure the gang is usually involved with, Freddie remains in the Mystery Machine while the rest of the team begin to investigate. Whilst Shaggy and Scooby get involved in some hi jinx involving the local fauna, Velma discovers that, indeed, if it weren’t for this dark matter and its associated gravity, most galaxies would fly apart due to their own velocity. Undaunted by Freddie’s petulant horn honking, Daphne’s general uselessness and Shaggy and Scooby’s cowardly antics, Velma carefully plans and executes a scheme whereby she successfully captures the dark matter. When the authorities show up Velma confidently lifts the mask off the dark matter revealing none other than Lou, the kindly innkeeper, whose motives remain unclear although they seem to involve treasure.

- – -

The Origins of the Universe

Having just returned from yet another battle with the Decepticons, Optimus Prime wearily examines one of the monitors in the communications room deep within Autobot City. He lets out a deep sigh as Jazz enters in a jubilant mood “That was some battle. We sure showed those bastards. High five?” Optimus is clearly in no mood and leaves Jazz hanging. It is awkward. “What’s wrong?” Jazz asks his beloved leader as he makes a move to suggest his hand had been raised in order brush back his hair.
“Do you ever wonder where we all come from?” the autobot leader is clearly in one of his moods.
“Cybertron,” replies Jazz confusedly.
“No no, I mean from where did the universe arise?”
“Well, extrapolating back from the known expansion of the universe we can imply that at the beginning of time all matter and energy were at an immense temperature and density.”
“Sure, but what happened prior to the big bang.”
Jazz has no immediate answer. Instead the two transformers stand silently. Optimus Prime gazes thoughtfully into space. Jazz brushes some dust off his shoulder and does some stretches.
“Maybe our universe’s initial hot, dense state arose from the collapse of a similar universe and there have been an infinite number of past bangs and crunches,” continues Optimus.
Jazz seems unconvinced and merely nods his head in an effort to convey his ambivalence.
“Of course I don’t want to preclude the existence of a creator God, we are after all giant robots, someone must have built us. Do you think that’s it?” Optimus asks.
“I’m a nihilist,” responds Jazz.
“Really?”
“Yep.”
“I didn’t know that.”
“Oh yeah, huge nihilist.”
“So you don’t believe in anything?”
“Well there are different schools of thought. First you can believe that nothing exists. Or you can think that the reality as we experience it does not exist. Personally I like to think that as reality is unknowable, pursuit of understanding is pointless.”
Again the two twenty foot robots stand in silence for some moments before Optimus breaks the stillness, “Good talk.” Deciding that the conversation has come to an end, Jazz transforms, with the accompanying beeps, into a Martini Porsche 935 Turbo and drives out of the communications room. Optimus Prime turns back to the monitor he had been examining.

- – -

Grand Unified Theory

The two scientists couldn’t help but feel vaguely disappointed. Finding this man had not been easy. They had been buoyed on their long journey by all the passer-bys who had said the one they sought would no doubt be able to help them to unify hypercharge, the weak force, and quantum chromodynamics. The imposing woman who lived in that castle had been especially convincing. Sure she seemed to be half falcon, but she had made some excellent points. And the large anthropomorphic bee they met had called him, “the most powerful man in the universe.” It was those kinds of endorsements that had kept the men going on their search. And now they had found him and he wasn’t what they were expecting. Firstly he was wearing a loincloth. It seemed unlikely that anyone wearing a loincloth would be intimately familiar with the vagaries of quantum mechanics. Also, he was sitting astride a panther.

“He man?” the first scientist timidly asked. “What can I do for you?” the large, half naked man, replied. The scientists then launched into a detailed description of their problem but soon trailed off as He-man went from being politely interested to manifestly confused before losing all interest and beginning to play with the giant sword he had strapped to his back. The talking skeleton had been right; this He-man character hadn’t been worth all the effort. The two scientists thanked He-man for his time and headed off dejectedly. They had heard some wonderful stuff about a woman named She-Ra, maybe they’d check that out.

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Patrick Francis is freakishly strong. However, his fighting technique is almost as bad as his dancing and so he would probably perform poorly in any sort of cage match. Also, he likes pie.

A LESS THAN FORMAL TREATMENT OF BIOLOGY CONCEPTS FOR THE BUDDING BIOINFORMATICS WANNABE

By Misbah Naseer

As a student assistant, I have been learning about bioinformatics for the last three months. During this time, I have found it to be an organization-obsessive rationalist in the house of sciences. It is not enough to get things right; you also have to arrange them in the proper order, and then try to make some sense out of them.

Not so strictly speaking, bioinformatics brings molecular biology and computer science together, often with the help of the unifying power of the mighty Internet. It stores the onslaught of biological data coming out of research labs and provides tools for interpreting and analyzing this data.

Now that I have become the only person knowledgeable in bioinformatics among my artsy friends, I am expected to know everything about biology AND bioinformatics (Boolean expression intended). So for the interest of those inquisitive minds who wish to increase their knowledge of biology, I have attempted to put together an informal list of general biological questions AND their relationship with bioinformatics.

1. What are DNA and RNA?
Deoxyribonucleic Acid (DNA) is found in the nucleus of cells. It carries the genetic information required for growth, development, and replication of an organism. DNA is a double stranded helical molecule made of subunits called nucleotides. Nucleotides are made of one of four bases (Adenine, Cytosine, Guanine and Thymine), deoxyribose (a sugar) and phosphate. DNA sequence is a shorthand notation of the base composition of a DNA molecule.

Ribonucleic Acid (RNA) is a single stranded molecule similar to DNA in structure, but has ribose in place of deoxyribose, and in most cases, has uracil in place of thymine. There are different types of RNAs including messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). RNA is synthesized from DNA by an enzyme called RNA polymerase and plays a number of important roles, most notably those involved in protein synthesis.

DNA and RNA sequences are fuels of bioinformatics, keeping it busy. Bioinformatics provides tools to store, interpret and analyze sequence data. It can find genes and the changes within them, relate them to one another, find similarity among them, predict their function and much much more.

2. What is the difference between a gene and a genome?
Genes are fundamental units of heredity. Alternatively, a gene can be thought of as a sequence of DNA nucleotides holding information about characteristics and biological function e.g. those that participate in eye or hair color, widow’s peak (v-shaped hair on forehead, I kid you not), height and even diseases like Hemophilia and Huntington’s disease. The complete set of genetic information (DNA) of an organism is called a genome. H.Influenzae was the first lucky organism to have all of its genes (~1700 of them) identified. The human genome project (HGP), which identified a whopping ~30,000 genes in humans, was completed in 2003. (More information about HGP can be found at the US Department of Energy’s Website, http://www.doegenomes.org/)

Genome data lets the fine folks in bioinformatics do what most tabloid reporters do i.e. find out more about the sequence in question, found out what type of relationships it might have, and quite likely produce unflattering pictures of them. Of course, bioinformaticians are expert reporters who gather all current information, dig up ‘old dirt’, and do not talk without some line of concrete evidence. See phylogeny if you really want to know more.

3. What is a model organism?
O.K. so I don’t look like Heidi Klum, but hey, turns out most of my genes are like hers. In fact, Heidi and I also share genes with some of our less sanitary neighbors living in garbage dumps, like fruit flies and mice. In essence, many fundamental biological aspects are conserved in organisms during evolution. However, it is obviously easier to study certain organisms than others. A model organism is therefore used for research in that it can provide insight into the biology of other organisms and also provide some semblance of convenience. In order to become a model you usually have to be small, readily available, easy to manipulate, and a quick breeder – all things that every CV should have. Once hired, models are (what else) manipulated and observed. Some famous names in the modeling world are Escherichia coli (bacteria), Saccharomyces cerevisiae (“baker’s yeast”), Drosophila melanogaster (fruitfly), Mus Musculus (house mouse), and Caenorhabditis elegans (roundworm). And of course, the perk for being a model organism – have all your genes identified! Mind you, they pay the price by being constantly hounded about relationships and the like (genetic ones only).

4. What is phylogeny?
The evolutionary relationship between different organisms is called phylogeny. Phylogenetic relationships can occur at many levels such as genes, proteins and species. Bioinformatics tools are used to find similarity in genes and identify evidence for the existence of common ancestors. These relationships are usually presented in the form of phylogenetic trees in which branches represent the divergence patterns of different organisms or parts of organism (e.g. genes). A web project featuring tree of life is currently in process of completion and can be accessed at http://tolweb.org/tree/phylogeny.html.

5. What are homologous genes/proteins?
Homologous genes/proteins have a common ancestor but they may or may not have a common activity. In bioinformatics, homologs are used to find phylogenetic relationships. Homologs can be searched using bioinformatics tools like BLAST, and Homologene.

6. Where did proteins come from? Isn’t bioinformatics about the genes?
Proteins are just as important as genes for bioinformaticians. Protein data is used to understand protein function, to make three-dimensional structures, to understand protein interactions, to even understand interactions between the cells of an organism. And similar to how kings conveyed messages to each other with the help of transcribers and translators in the old days, proteins are produced from genes via both transcription and translation processes. Specifically, this is a two-step process in which both DNA and RNA are involved to assemble amino acids (the building blocks of proteins).

First, a gene from DNA is transcribed into mRNA. Next, mRNA uses something called ribosome to translate RNA into amino acids, which subsequently join together to form proteins. To understand this process visually, it is perhaps best to see a simple animation developed at University of Nebraska. For the enthusiasts wanting more details, there is a detailed animation featured at ‘Biology’ (textbook) website. (Click on protein synthesis).

7. What is alternative splicing?
A gene is first transcribed as pre-mRNA from the DNA. Briefly, in eukaryotic cells, pre-mRNA has intronic regions (which are considered non-coding) and exonic regions (which are considered to be coding). Intronic regions are removed or spliced from the mRNA, whereas combinations of the exonic regions are retained by the final mRNA product. This splicing process and combinatorial approach can yield different mature mRNAs. In turn, this will lead to the translation of different proteins with potentially different functions – all originating from the same gene. It allows complexity in genomes because one gene actually has the potential to make many proteins. Just think of the possibilities!

8. How can I find a protein sequence or a gene sequence?
There are many searchable databases available to the public for searching a sequence. A comprehensive list of protein and nucleotide databases can be found at Expert Protein Analysis System (Expasy)’s website at www.expasy.org/links.html. Do not let the length of the list scare you. Databases are our friends.

9. What is a mutation?
Any change in the DNA sequence is called a mutation. It may be caused by external factors such as ultraviolet rays or it can be a result of error during DNA or protein synthesis. A change in DNA may lead to the production of incorrect or non-functioning proteins. (Mutations may or may not grant ‘X-Men’ status.) Depending on the importance of the biological function of the protein in the organism, mutations can cause genetic disorders and disease and are, therefore, studied extensively. To read more about different types of mutations, and diseases caused by mutations, visit 2can, the European Bioinformatics Institute’s educational website.

So there you have it—a smattering of some of the concepts that appear frequently when exploring bioinformatics. The list is not complete by any chance. Heck, it will just keep growing once you dive in the field but that’s the whole point of learning – to learn new things (and brush up on stuff you thought you were never going to see again in life). Enjoy the thrill ride!

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Misbah has been on the Earth for 20 years as the daughter of brilliant parents; is married to her soulmate; has the nickname "geek" via her two brothers; is currently in the final year of her Bachelors of Integrated Sciences at UBC; is working as a student assistant at the UBC Bioinformatics Centre; is a computer lab attendant at UBC-Arts ISIT; is an assistant editor for 'The Miracle'; (and) would like to end this bio by listing a few interesting injuries (needle in foot for 21 days at age 13, and a twice scratched cornea).

HARMONY IS ALWAYS HERE

By David Ng

The SCQ would like to introduce a new category, which we have tentatively called “impressions.” Think of it as an avenue to reflect on the music, words, or film that affect your relationship to science or your relationship to something that entails a small link to science. Hmmm, is that vague enough?

- – - – -

I’m not entirely sure if I became a rational scientific person by nature or nurture. Whether it is genetic or whether it is the obvious result of too many years of study. Whatever the case may be, I am a slave to my curiosity, and sometimes I swear I bleed science. To me, everything needs an answer, deserves an explanation, or craves a solution. Even Ben.

And it would not be a stretch to say that I have known Ben for his entire life. In fact, I was even there at his birth – an intense, wet and happy event that will forever resonate in my head. Not all that surprising when you consider that Ben is only 12 months old and also my son. And as a father, I know that children are truly marvelous creatures – they are like noisy habits, capable of providing endless emotion, delivering that bullet of equal parts joy, worry and fatigue.

They are also mysterious to me. Not in the sense that being a parent fills me with fear, but more in the sense that I am often in wonder at how perfect these small beings really are – a testament, if you will, to the marvel of biology. I mean really, what exactly makes them do the things that they do?

Take music, for instance – it reaches out to Ben. And for whatever reason, certain songs can even elicit specific fervent reactions. Although the examples seem to change weekly, currently they include: Vertigo by U2 (spontaneous heading bobbing – head banging really), Won’t Give In by the Finn Brothers (spontaneous twirling/cuddling), and the Dora The Explorer Theme Song (spontaneous manic hip swaying) – all in a child that is a little over one year old.

It is really quite amazing to behold and so I find myself compelled to ask (as a scientist would tend to do), “Could there really be something biological about music?” A question that, surprisingly enough, is not such a silly question after all. Consider:

People use music therapy to help them cope.
People make their children listen to Mozart.

Still, the skeptic in me takes pleasure in scorning such things. But even I have to concede that it all sounds more or less reasonable. Especially so when you realize that in essence, these statements only rely on the simple inference that some things happen to sound right, whereas other things happen to sound wrong – an unobtrusive statement that in science-talk translates to the phenomenon of sounds being either consonant (pleasant) or dissonant (unpleasant).

But this inference solves nothing. Further, it does not make me understand my child better. So I dig deeper. And I learn that there is an astonishing amount of research in this matter.

People monitor brain activity under difference musical note combinations.
People follow prenatal, neonatal and infant stages of music development.
People compare vocal abilities between various organisms.
People study song structures from various different ethnic and cultural populations.
People search for similarities between language and musical consonance.

In fact, there is so much research that it becomes almost common to hear of the “universality of music.” A phrase that I suppose suggests a special, maybe holy link between music and biology, between music and nature. Maybe even God is at play here. Indeed, studies do exist that contend some truly grand links between music and nature.

People have shown that aspects of musical prowess are genetic in nature.
People have used DNA code to compose musical works.

But God is not an explanation in itself. Not for me anyway. Not today. And while this hunt for answers thrills the scientist in me, the fact that they still remain elusive leads only to frustration.

Concerning the three songs mentioned above. Perhaps, I should ask Bono himself. He is undoubtedly someone who has an inordinate degree of perspective. As a musician, global icon, humanitarian, and parent it wouldn’t surprise me if he, himself, had some wise words on the matter. And truth be told, I’d also be curious to hear what Neil and Tim Finn would have to say, given their brotherly genetics and their ability to craft those near perfect melodies.

But ironically, in the end, I suspect that it is what Dora the Explorer has to say that is most prevalent – which, given her being a cartoon and all, is to say that nothing should be said. That perhaps with music, elements of logic and calculation needn’t get involved; that with music, science is beside the point.

And even though such an assertion personally breaks my scientific heart, I feel it has merit. I feel it when I see Ben move his head to the loud rhythms of Vertigo, an action made all the more fiercely expressive when he is in our car, restrained by his baby seat. And I feel it especially in those precious moments just before bedtime, listening to Won’t Give In, when he chooses to hold me tightly like I’m the only thing that matters in the world.

These are the moments when I realize a new possible truth. And that truth is this – that although the relentless pursuit of knowledge is widening my eyes and mind, I am perhaps losing my soul in the process.

But really, this is just another hypothesis. So for now, I take comfort in knowing at least one thing. I know that for the rest of my life, whenever I hear one of Ben’s favourite songs I will think only of him. And thankfully for now, that is something I’m pretty sure has nothing to do with science.

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David is Director of the Advanced Molecular Biology Laboratory, the educational arm of the Michael Smith Labs. He's also the dude that edits the SCQ. You can follow David on twitter at http://twitter.com/dnghub

THE GIRAFFE: A FAVOURITE TEXTBOOK ILLUSTRATION OF EVOLUTIONARY THEORIES

By Richard Peachey

High-school biology texts regularly present Darwin’s theory of evolution in contrast with Lamarck’s earlier explanation, and the organism most often used to illustrate the difference between the two views is the giraffe (e.g., Creager et al., pp. 233-240). Lamarck, it is said, told a story of giraffe necks becoming longer as the animals tried to stretch their necks to reach food (Law of Use and Disuse). The longer necks acquired in this way would then be passed on to their offspring (Law of Inheritance of Acquired Characteristics). Continued stretching over the generations led to today’s long-necked giraffes. Darwin, on the other hand (it is said), proposed that early giraffes had necks of different lengths, some longer and some shorter (Variation). Limited food supplies meant that not all giraffes could obtain enough food to survive (Competition). Giraffes with longer necks could survive better and reproduce, passing their long-necked trait to their offspring, while those with shorter necks more often died off before being able to reproduce (Natural Selection). Over the generations the average giraffe neck became longer due to this process. But a number of things are wrong with this story:

1. Historically, there is no evidence that either Lamarck or Darwin used the giraffe as a significant part of their presentation of evolution. In his sixth edition of Origin of Species (though not in the first five editions), Darwin (201-203) did discuss the giraffe’s neck, as part of a new section attempting to refute St. George Mivart’s objections to the theory of natural selection (Gould 54). But then, Darwin explicitly accommodated Lamarckian thinking in his explanation; he accounted for the giraffe using natural selection “combined no doubt in a most important manner with the inherited effects of the increased use of parts” (202, cf. 133-139). The late Harvard evolutionist Stephen Jay Gould states: “When we look to presumed sources of origin for competing evolutionary explanations of the giraffe’s long neck, we find either nothing at all or only the shortest of speculative conjectures. . . . The giraffe’s neck just wasn’t a big issue for the founders of evolutionary theory—not as a case study for arguing about alternative mechanisms, not for anything much at all. No data from giraffes then existed to support one theory of causes over another, and none exist now” (21).

2. Female giraffe necks, on average, are two feet shorter than male necks! “If a longer neck were needed to reach above the existing forage line, then the females would have soon starved to death and the giraffe would have become extinct” (Davis and Kenyon 71).

3. Many researchers now suggest that the primary function of giraffe neck length is not for reaching leaves on tall trees, but for male combat (“necking”), or for spotting predators, or for shedding heat through increased skin surface area. All of these functions “have been viewed by prominent scientists as a chief reason for the evolution of the long necks” (Gould 56f.). Darwin himself (202) alludes to some of these as alternate possibilities.

4. There is no fossil record showing a gradual increase in giraffe neck length. “All giraffes belong to a single species, quite separate from any other ruminant mammal, and [allegedly] closely related only to the okapi (a rare, short-necked, forest-dwelling species of central Africa). Giraffes have a sparse fossil record in Europe and Asia, but [alleged] ancestral species are relatively short necked, and the spotty evidence gives no insight into how the long-necked modern species arose” (Gould 56).

5. The giraffe neck is not simply a longer version of an okapi neck; it is a well-designed “adaptational package” — a combination of unique features that work together to help the giraffe survive in its environment:

“To drive blood eight feet up to the head, the heart is exceptionally large and thick-muscled, and the blood pressure—twice or three times that of a man—is probably the highest in any animal” (Foster 409). “When a giraffe is standing in its normal erect posture, the blood pressure in the neck arteries will be highest at the base of the neck and lowest in the head. The blood pressure generated by the heart must be extremely high to pump blood to the head. But when the giraffe bends its head to the ground it encounters a potentially dangerous situation. It must lower its head between its front legs, putting a great strain on the blood vessels of the neck and head. The blood pressure plus the weight of the blood in the neck could produce so much pressure in the head that the blood vessels would burst. Mercifully, however, the giraffe is equipped with an adaptational package, including a coordinated system of blood pressure control. . . . Pressure sensors along the neck’s arteries monitor the blood pressure, and can signal activation of other mechanisms to counter any increase in pressure as the giraffe drinks or grazes. Contraction of the artery walls [which have increased muscle fibre toward the head], a shunting of part of the arterial blood flow to bypass the brain, and a web of small blood vessels (the rete mirabile, or ‘marvelous net’) between the arteries and the brain all serve to control the blood pressure in the giraffe’s head. Notice that adaptations require other adaptations so that a specialized organism such as the giraffe can function optimally” (Davis and Kenyon 71). The giraffe also has special “control valves in the jugular veins” (Foster 409); these “heavily valved veins control return of blood to the heart” (Davis and Kenyon 70).

“The lungs are oversize to compensate for the volume of dead air in the long trachea. Without this extra air-pumping capacity a giraffe would breathe the same used air over and over” (Foster 409). “The giraffe’s lungs are eight times the size of those of humans, and its respiratory rate is about one-third that of humans. Breathing more slowly is necessary in order to exchange the required large volume of air without causing windburn to the giraffe’s rippled 3.6 metres (12 feet) of trachea. When the animal takes in a fresh breath, the oxygen-depleted previous breath cannot be totally expelled. For the giraffe this problem is compounded by the long trachea that will retain more dead air than man can inhale in one breath. There must be enough lung volume to make this ‘bad air’ a small percentage of the total” (Hofland 12).

“Equally marvellous is the fact the blood does not pool in the legs, and a giraffe does not bleed profusely if cut on the leg. The secret lies in an extremely tough skin and an inner fascia [fibrous connective tissue] that prevents blood pooling. This skin combination has been studied extensively by NASA scientists in their development of gravity-suits for astronauts. Equally helpful to prevent profuse bleeding is that all arteries and veins in the giraffe’s legs are very internal. The capillaries that reach the surface are extremely small, and the red blood cells are about one-third the size of their human counterparts, making capillary passage possible. It quickly becomes apparent that these unique facets of the giraffe are all interactive and interdependent with its long neck. But there’s more. The smaller red blood cells allow for more surface area and a higher and faster absorption of oxygen into the blood. This helps to retain adequate oxygen to all extremities, including the head” (Hofland 12).

References
Creager, Joan, Paul G. Jantzen, and James L. Mariner. 1985. Biology. New York: Macmillan.

Darwin, Charles. 1958. Origin of Species. (reprint of 6th edition). New York: Mentor.

Davis, Percival, and Dean H. Kenyon. 1993. Of Pandas and People. 2nd edition. Dallas: Haughton Publishing. See especially pp. 12-13, 69-71.

Foster, Bristol. 1977 (Sep). Africa’s Gentle Giants. National Geographic Vol. 152, No. 3. pp. 402-417.

Gould, Stephen Jay. 1996 (May). The Tallest Tale. Natural History Vol. 105, No. 5. pp. 18-23, 54-57.

Hofland, Lynn. 1996 (Sep-Nov). Giraffes: animals that stand out in a crowd. Creation Vol. 18, No. 4. pp. 11-13.

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(REPRINTED FROM ISSUE ONE, JUNE 6th, 2005)

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Richard Peachey is a public school science teacher with a background in biology and chemistry. He finds himself in agreement with T. H. Huxley and E. O. Wilson, both of whom dismissed the logical possibility of believing evolution and the Bible at the same time. Formerly a friend of the prevailing evolutionary worldview, he now takes his stand with the Bible, and with Jesus Christ, who taught concerning humankind, "At the beginning the Creator made them male and female."

 



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