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Monthly Archives: April 2013

A suggestion and a request

As you can see from my previous post, my general bio class has been delving into the molecular mechanisms of replication, transcription and translation. All of these processes were worked out in the latter half of the 20th century following the publication of DNA’s structure by Watson and Crick. Because Watson and Crick’s work was so seminal, it seems reasonable for me to make a couple of book recommendations relating to that work. ImageThe first is The Cartoon Guide to Genetics.  With a title including the word ‘cartoon’, it is tempting to dismiss this book, but you would be doing yourself a disservice. This is one of the most clearly written genetics books you can ask for. Despite the apparent simplicity, it is surprisingly thorough. I am presently considering making this book required reading for a genetics / ecology course I am planning.

Another book is James Watson’s The Double Helix. This book is short and an easy read, yet it puts you right in the center of the Imageaction – both scientific and personal – that surrounded the elucidation of this molecule’s structure.

This brings me to my request… As I mentioned above, I am working on a new course which will act as a second semester to my current general bio class. The main topics of this class will be inheritance, population genetics, the dynamics of populations and how all this informs our knowledge of evolution. I have a couple ideas already, but I thought I would open this space up to accept any suggestions the peanut gallery may have. If you have a book that you like that was a good read and brought up some interesting conversations, let me know and I’ll check it out.

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Posted by on April 30, 2013 in Uncategorized

 

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DNA –> RNA –> Protein (in greater detail)

I emphasize the importance of ‘the central dogma’Image pretty regularly throughout the semester in General Biology. This idea represents one of the core theories of biology and helps to explain an enormous amount about life. This ‘dogma’ explains how the information contained in DNA is replicated prior to cell division – and used to make drafts of that information (RNA) that can guide the construction of proteins that get the work of the cell done.

In the current unit, we are expanding this theory and examining the processes and the molecules they create more closely. Fortunately, each of these processes is elegantly illustrated in a set of animations available on the HHMI website.

The first video presents a model of replication. The model (as shown) is correct in its idea, but is not intended to be a model of HOW replication occurs, only how, in the words of Watson and Crick, “… [T]he specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

http://www.hhmi.org/biointeractive/media/DNAi_replication_schematic-lg.mov

The actual mechanism of DNA replication is complicated by the anti-parallel arrangement of the paired DNA strands and the fact that DNA Polymerase, the enzyme responsible for copying the DNA, can work only in one direction.

The action of the DNA polymerase, along with some additional enzymes (Helicase and Ligase) is illustrated mechanistically in the following animation:

http://www.hhmi.org/biointeractive/media/DNAi_replication_vo2-lg.mov

Screen Shot 2013-04-30 at 6.36.15 PMOnce DNA is replicated, during S Phase of the cell cycle, the cell is ready to divide and provide one complete copy of the DNA to each of the two daughter cells. In this way, DNA replication allows for the continuity of genetic information from one generation (of cells or whole organisms) to the next.

Throughout the cell’s life, it is necessary to produce proteins to accomplish the work of that particular cell. Again, the information contained in the DNA is copied, this time to a messenger RNA (mRNA) strand, and the instructions to make the protein are carried into the cytoplasm. This process, called Transcription, is carried out primarily by the enzyme, RNA polymerase, as illustrated below:

http://www.hhmi.org/biointeractive/media/DNAi_transcription_vo2-lg.mov

Once an mRNA is constructed, it is transported from the nucleus (where the DNA resides) into the cytoplasm. There, a Ribosome will coordinate the recruitment of transfer RNAs (tRNA) bearing specific Amino Acid building blocks called for to synthesize the protein. This process, called translation, is illustrated by HHMI below:

http://www.hhmi.org/biointeractive/media/DNAi_translation_vo2-lg.mov

 
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Posted by on April 29, 2013 in Uncategorized

 

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A quick description of Lymphocyte Development and Activation

Lymphocytes Development and Activation

Lymphocytes (B cells and T cells – we’ll not talk about NK cells here) go through a generalizable sequence of maturation events. Each starts in the Bone Marrow (BM) as a Hematopoietic Stem Cell (HSC), where it starts its development. T cells leave the BM relatively sooner and go to the Thymus, while B cells remain in the BM for most of their development and then finalize development in the spleen.

 Positive Selection for BCR/TCR Development

Regardless of the type of cell (T or B), development occurs in two stages – First, each cell will attempt to make a unique lymphoid receptor (B cells have a BCR; T cells have a TCR). In order to do this, genetic material must be shuffled. While this shuffling does randomize the binding pocket of the lymphoid receptor, it may also destabilize these same receptors’ structure. To account for this, lymphocytes undergo a ‘positive selection’ period that ensures that a viable receptor is formed. This is actually done twice: once to ensure that a ‘Pre-Lymphoid Receptor’ is formed and again to for a ‘Mature Receptor.’  However, both are considered positive selection. Failure to pass this selection point leads to death of the cell. (In the figure below, Pre-Lymphocyte receptors are colored red, mature receptors are grey)

Negative Selection Against Self-Reactive BCR/ TCRs

Once cells have survived positive selection, they are considered Immature Lymphocytes. Although the terminology is poor here, these immature cells have mature lymphocyte receptors. At this point, these receptors have to be tested against all possible ‘Self ‘- antigens. In this case, binding means that these cells have the potential to react against the self – this is a no, no. The Immune System turned against the self is extraordinarily dangerous. Therefore, self-reactive cells are eliminated during this negative selection process. (In the figure below, mature lymphocytes have grey nucleus, all prior stages have red nuclei).

LymphosFollowing these developmental stages, the cells that have survived both positive and negative selection are 1) stable, mature lymphocyte receptors and 2) not reactive to ‘self’. These cells then enter the immune repertoire for that organism and are available to react against any foreign threats. Again, it is important to emphasize that each lymphocyte has a unique receptor and therefore will only get activated by a unique foreign antigen.

I may write more later to discuss some of the details that distinguish B and T cell development, but for now, this generalizable description will suffice.

Clonal Selection

Once a part of the immune repertoire, lymphocytes are on the lookout for foreign antigen that is capable of being bound by that cell’s receptor. Depending on the cell type, this interaction may be in one of several contexts (either in the context of MHC I, MHC II or as a naïve, soluble antigen), but regardless of the context, these ‘naïve’ lymphocytes will become activated by binding of their lymphocyte receptor. And once activated, lymphocytes will proliferate and differentiate. Differentiation typically goes in one of two general directions:

1)   generating activated effector cells (these secrete antibody if B cells, kill target cells, if CD8 T cells, or become helpers if CD4 T cells)

–or-

2)   generating memory cells, cells that act the same as the mature naïve cell that was activated, but are more numerous and can, themselves be activated upon stimulation.

An example of this activation is shown below in this HHMI video about how CD8 T cells can be stimulated to activate and then kill any target cells. This video also does a good job of illustrating how antigens get digested within a cell and expressed in the context of MHC I.

http://www.hhmi.org/biointeractive/media/antigen_ctl-lg.mov

 
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Posted by on April 25, 2013 in Uncategorized

 

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Colour Vision

I stumbled upon this essay on color vision and wanted to point it out. Also take a look at my own previous posts on color vision at https://downhousesoftware.wordpress.com/2013/02/13/3298/ and https://downhousesoftware.wordpress.com/2012/09/28/natures-hidden-beauty-a-tangent-from-intro-bio/

standingoutinmyfield

There has been a perfect storm leading up to this post.  It was just inevitable that I tackle the topic, because of several coinciding factors.

The first factor is that it is SPRING and the world is erupting in rich colours, vibrant pinks, baby leaf greens, and the subtle blush of red maples flowering in the mountains.

The second factor is that I have been running long distances, and when I run long distances, I like to listen to science-based radio shows.  Which means that I have been listening to podcasts of Radio Lab for solid hours on end.  It is a popular NPR radio show, and it has one of my favourite science writers, Robert Krulwich, and his charismatic co-host Jad Abumrad.

The third factor was this excellently written post by an online comic artist Matthew Inman on Mantis Shrimp.  If you haven’t read that strip…

View original post 347 more words

 
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Posted by on April 25, 2013 in Uncategorized

 

The Curse of Sisyphus -Coming Soon to iTunes

ImageThe Curse of Sisyphus, from DownHouse Software is coming soon to iTunes.

Sisyphus’ is a tale of cleverness and cunning in which the malevolent King Sisyphus offends  and then repeatedly infuriates Zeus  until the King of the Gods is forced to personally curse Sisyphus to a punishment befitting his crimes: To slave beneath a stone, pushing it each day to the peak of a great mountain in the underworld and then have it come crashing down upon him, leaving him to repeat the task again … and again … and again, throughout eternity.

But Zeus has tried to hold Sisyphus captive before only to find that the clever human is not so easily trapped.

In this volume, Sisyphus taps into the vengeance of scorned brother, the wisdom of an oracle and the might of a demigod as he masters the rules governing gravitation and motion to escape his punishment.

Look for it in the iTunes book store this May.

 

Also, take a look at In Parts: A Tale of Fractional Zombies, free in the iTunes Bookstore now until Saturday!

 
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Posted by on April 23, 2013 in Uncategorized

 

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I’ve been thinking about Tylenol a lot lately.

ImageHaving only recently recovered from the Flu, the constant headache I’ve been suffering for the past 24 hours may well be due to my inability to keep up with a healthy intake of caffeine while ill. My wife assures me, that with a conscientious recaffeination strategy I can be well on the road to wellbeing soon enough.

That’s good. Hopeful, even.

ImageAnd if the constant headache makes me question the meaning and value of life, then it’s a comfort to know that a dose of acetaminophen can help with the headache AND with the existential angst. The Psychological Science paper, The common pain of surrealism and death: Acetaminophen reduces compensatory affirmation following meaning threats tells us not to worry about existence… pop a pill. Well, they don’t actually say that, but they do offer evidence suggesting that it may help.

The research by Daniel Randles, Steven J. Heine and Nathan Santos of the University of British Columbia, is based on the Meaning Maintenance Model (MMM), which “focuses on people’s compensatory responses to violations of expectations, termed meaning threats. The model argues that any perceived meaning threat produces unpleasant arousal that often lies outside of awareness, and is non-specific to the causal stimulus.” They explain that people will respond to these disturbances  “by affirming any available unrelated schema to which they are committed. These affirmations of intact meaning frameworks serve to dispel the unpleasant sense that something is wrong.”

To test this, among other things subjects were exposed to David Lynch’s Rabbits, which is defined by its lack of any discernable meaning (vs a control screening) and then either given 1000mg of acetaminophen of placebo.

Now here’s the fun part. How do people respond to disturbances of meaning (AKA existential angst)? Right, by affirming any available unrelated schema… like, say, the criminal justice system. Because the study was taking place soon after a riot incited by the Vancouver Canucks failure to claim the Stanley Cup, students were asked how severely rioters should be punished.

You know the answer, it’s in the title, but by how much?

ImageNo kidding?! – Watching David Lynch really makes people that much more likely to serve up stiff sentences? Whaddayaknow.

I found this article to be really entertaining. Another common method for testing people’s meaning – threats is to ask how high bail should be set for someone being tried for prostitution. How can you not read this stuff? You can download a copy of the original article as a word doc here. Or read someone else’s account of it here.

 
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Posted by on April 22, 2013 in Uncategorized

 

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On a lighter note…

I always like to point out this video to my students. One can only fully appreciate it once one has been under that particular wheel, but here it is nonetheless:

 
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Posted by on April 21, 2013 in Uncategorized

 

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