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<docHead>
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<title>How Toxins Work (Blog Post - WP2)</title>
<author xml:id="g14">Benjamin Gincley</author>
<version n="1" date="2016-07-31"/>
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</docHead>
<blog_post>
<background>
<pb/><section_header>How does venom work?</section_header>
<question>Are there different kinds and why are some animals resistant or immune to the
venom?</question>
<pb/>
<technical_principle n="1">Venom is a mixture of chemicals that different organisms have
evolved to use as a defense mechanism or to immobilize prey. <important_idea n="1"
>There are different kinds of venoms, namely, neurotoxins (that affect the
nervous system and cause paralysis, convulsions, etc.) and haemotoxins, which
affect the blood (prevent clotting, etc.).</important_idea> We'll focus on
neurotoxins.</technical_principle>
<misconception n="1">One common misconception people have is the difference between
venom and poison. <important_idea n="2">Venom is dealt by biting, stinging, or
otherwise injecting into body tissue through a wound, while poison is a secreted
toxin that, when ingested, inhaled, or absorbed, delivers its
effects.</important_idea><analogy>For example, people can eat many venomous
snakes and scorpions because they do not secrete their toxin onto their skin or
other body tissues. Poison ivy secretes its toxin onto its leaves, and doesn't
go around trying to bite or sting people.</analogy></misconception><pb/>
<visual type="comic"
url="http://www.birdandmoon.com/wp-content/uploads/2015/07/toxic.jpg">Comic courtesy
of birdandmoon.com</visual>
</background>
<answer>
<pb/>
<section_header>What, basically, is going on?</section_header><technical_principle n="2"
>Understanding how neurotoxins work relies on a basic understanding of neurobiology.
Nerve cells in the body, be they in the brain, spinal cord, or connecting to your
muscles, rely on a combination of chemical and electrical signals to transmit
information from one cell to the next and one part of the body to the next. Cells in
the body exist in a fluid matrix that contains all sorts of different chemicals, and
the concentration of these chemicals is often different inside and outside of the
cell's membrane that separates it from the rest of the world. Many of these
particles are ions, meaning they lack or possess extra electrons, effectively giving
them an electric charge. When the concentration of these ions is different inside
and outside of the cell, it creates a difference in potential charge, called the
Resting Membrane Potential.</technical_principle><specific_topic n="1">Cells possess
tiny channels in their membranes that allow these ions to travel into and out of the
cell, which effectively changes the electrical potential difference between the
inside and the outside of the cell. These channels can be opened either by a change
in the electrical potential in the membrane, or by the presence of a particular
chemical that causes them to change shape and open or close them. The act of opening
or closing many of these channels at once results in a sudden transfer of ions into
or out of the cell, which often changes the balance of charge that was maintained
and therefore causing the voltage across the membrane to
spike.</specific_topic><important_idea n="3"> The key ions used by neurons are
potassium ions and sodium ions.</important_idea><pb/><visual type="drawing"
url="https://dundeemedstudentnotes.files.wordpress.com/2012/04/picture22.jpg"
>Depiction courtesy of dundeemedstudentnotes.wordpress.com</visual><pb/>
<important_idea n="4">The core unit of transmission is called the Action Potential, in
which there is a sudden change in this electric potential in a local area of the
cell, and the arrangement of channels in the cell membrane allows for this local
change in potential to propagate, or travel down, the length of the cell
membrane.</important_idea>
<technical_principle n="3">Neurons contain a long extension called an axon, which allows
this current to travel a relatively far distance before reaching the end of the
cell. Once it reaches the end of the cell, the current arrives at a synapse, or a
gap between the current cell and the next one. The current has no place left to go,
as it has reached the end of its cell, but at the synapse there are structures that
can secrete chemicals called neurotransmitters.</technical_principle><pb/><visual
type="drawing"
url="https://figures.boundless-cdn.com/19537/full/figure-35-02-04.%402x.png"
>Depiction courtesy of Boundless.com, The Nervous System, Figure 35.</visual>
<specific_topic n="2">These neurotransmitters can leave the cell, travel through the
intercellular space, and make contact with the cell on the other side by interacting
with receptors on the next cell's membrane. These receptors respond uniquely to the
neurotransmitters they are designed to bind with,</specific_topic>
<important_idea n="5">but it is important to note that what is occurring is an
interaction between complementary shapes, meaning that if a different molecule had a
region that was similar in shape to the neurotransmitter in question, it too would
interact with the receptor.</important_idea><pb/><visual type="drawing"
url="http://www.daviddarling.info/images/neurotransmitter.jpg">Drawing courtesy of
daviddarling.info.</visual><pb/><analogy>Imagine the shape-fitting toys that
toddlers play with, where you insert a triangle or a circle piece into various
cutouts, trying to match the correct shape with the correct hole. The
neurotransmitter is the inserted piece, and it only inserts into the correct hole,
or receptor. As an example, let's say the neurotransmitter dopamine is a triangle
piece, and serotonin is a circle. Dopamine will only fit in the triangle receptor,
and serotonin will only fit in the circle receptor<note type="instructor"
resp="#kgs">OK nice work! I really needed this at this point, I was beginning to
get lost (as a total outsider to this field).</note>.</analogy>
<technical_principle n="4">Once activated, the receptor continues the signal cascade in
the next cell, either chemically or electrically, furthering the transmission of the
signal to its destination, whether it be to the brain to signal something, or to a
muscle to tell it to move.</technical_principle><pb/><visual type="drawing"
url="http://i.imgur.com/LsVfrJu.png">In this case, the "triangle" dopamine only fits
in the correct "triangle" receptor.</visual><pb/><analogy>Now consider a modified
version of the shape matching toy mentioned earlier where instead of falling through
the hole, the insert has a larger block connected to it, so the piece inserts where
the shapes match but the rest of the piece hangs out. The natural neurotransmitter
is a triangle inserted into a triangle hole successfully, but there can be other
chemicals that can interact with the board too. Another piece with a triangle that
fits the hole is referred to as an agonist (one that binds successfully to the
receptor), and a piece that partially fits the hole but doesn’t fit perfectly and
prevents other pieces from fitting is referred to as an antagonist (obscures the
receptor without activating it).</analogy><pb/><visual type="drawing"
url="http://i.imgur.com/5IeQkm4.png">Other shapes, like a "trapezoid"-shaped
chemical, can also fit into the "triangle" dopamine receptor, activating
it.</visual><pb/>
<explanation n="1">Neurotoxins are molecules that affect the chemical transmission
between neurons, by affecting the cell transmitting the chemicals (pre-synaptic) or
receiving them (post-synaptic). Some neurotoxins like tetrodototoxin (TTX), which is
found in pufferfish and poison dart frogs, acts by blocking the sodium channels in
the pre-synaptic cells. <analogy>TTX is a large chemical (compared to a sodium ion)
that attaches to the channel and stops it like a cork for tens of seconds at a
time.</analogy> This blockage prevents sodium ions from entering the cell, and
as a result, the cell can no longer transmit action potentials. Contact to your
hands would cause paralysis, as even though your brain is telling your hand to move,
the message stops upstream of the muscles, and they do nothing. The toxin becomes
fatal when it reaches critical tissue like the heart or lungs, where the stoppage of
the involuntary nerve impulses that tell your lungs to expand and contract or your
heart to beat causes those organs to become paralyzed. Then you die.<note
type="instructor" resp="#kgs">well there it
is.</note></explanation><pb/><explanation n="2">Other toxins can interact with other
ion channels or receptors to produce various effects, some of which can become very
complicated and involved. Some toxins like tetanus bind to presynaptic inhibitory
interneurons (neurons that release chemicals to other neurons to prevent them from
firing action potentials), resulting in repeated muscle spasms because they can't
"turn off" the muscular neurons. This ultimately leads to paralysis. Overall, most
neurotoxins lead to paralysis in one way or another, and nature has come up with
creative ways to cause this from perceivably every angle that it possibly can.<note
type="instructor" resp="#kgs">so every way it can interact with the shape board
that you talke about?</note></explanation><pb/><explanation n="3">Why some
animals are immune or resistant to toxins, animals like the mongoose that can
sustain repeated cobra bites, comes down to shape, once again<note type="instructor"
resp="#kgs">I like that you pull this thread through</note>. These animals have
evolved channels and/or receptors that have a slightly different shape that prevent
the toxin from interacting, while continuing to allow the normal molecules to do
their thing. Let's return to our original analogy. <analogy>Imagine if the triangle
hole now had a circular bump around it that prevented larger pieces from staying
in place. The normal piece can still fit fine, but now the toxin piece can no
longer fit properly because of the bump.</analogy> Toxin can't bind, toxin can't
block the channel, toxin can't prevent the cell from signaling, and the mongoose
goes on its merry way getting bit by cobras. It's not immune, as given enough toxin
pieces, eventually as soon as one comes off, another toxin piece takes its place,
and the cell can't take in sodium fast enough for an action potential, but the
animal is at least resistant to a few bites.</explanation><pb/><visual
type="drawing" url="http://i.imgur.com/9YFCOhI.png">If the organism evolved a raised
"ring" around the "triangle" receptor, molecules with other shapes that hang off the
side would bind briefly, then fall off.</visual>
<conclusion><pb/><section_header>So, how does venom
work?</section_header><important_idea n="6">Venom is a chemical compound that
interacts with receptors and channels in nerve cell membranes that disrupt the
transmission of messages, namely via action potentials, between the
neurons.</important_idea> This often results in paralysis in some way or
another, as the messages from the brain or spinal cord can no longer get to the
muscle tissue. The result, a paralyzed animal that either can't move and is much
easier to kill, an animal who suffocates to death because their lungs can't move, or
a potential predator that now has a paralyzed arm or tentacle and won't come near
you ever again (or probably survive much longer). <important_idea n="7">Animals can
resist these toxins by changing the shape of their receptors or channels so that
the toxins can no longer bind to them or block
them.</important_idea><pb/><visual type="photo"
url="https://i.ytimg.com/vi/lsLdLKATnyk/maxresdefault.jpg">Image courtesy of
Super Lion's YouTube video</visual><note type="instructor" resp="#kgs">cool
picture</note></conclusion>
</answer>
<pb/><sources>Depending on your neurobiology experience, a myriad of sources can elucidate
the mechanisms involved in various toxins. <ref type="source"
url="https://bigpictureeducation.com/venoms-and-nervous-system">Big Picture</ref>
provides some nice introductory/summary information on neurotoxins and some examples.
Rose Eveleth with Ted Ed does a great job explaining what the difference between poisons
and venoms are in a <ref type="source"
url="http://ed.ted.com/lessons/venom-vs-poison-what-s-the-difference-rose-eveleth"
>fun and informative video.</ref> Toxipedia is a <ref type="source"
url="http://www.toxipedia.org/display/toxipedia/Neurotoxins">fantastic resource for
more information</ref> on neurotoxins, providing lots of different mechanisms that
have been discovered so far. For more info on TTX, the quintessential neurotoxin used in
examples, <ref type="source"
url="http://www.life.umd.edu/grad/mlfsc/zctsim/ionchannel.html">see here.</ref>
</sources>
</blog_post>
<docReview>
<note type="peer" resp="#g14"> *Answer to Kevin's Questions On Board* So far, the overall
flow and inclusion of elements is going well, and I feel that I have made a good effort
to use all of the elements we included in the schema that have relevance to the post.
The difficulty has mostly been formatting with images, understandably, in that sizing
and centering/placement is not ideally accounted for in the source code. I feel I am
nearly finished in the process, and am open to suggestions to clarify content or include
more elements as necessary. Of particular note might be the picture at the end that is
way too big for the space, and might want to try to create a smaller version of the
image to use. Also, I added captions to some images to accredit them, including the text
in the visual element, but they don't appear in the formatted version. I should look
into getting those captions printed on the screen. I am also open to suggestions about
how I handled the sources section, as I used the informal annotation paragraph with
links style as opposed to a formal citation.</note>
<reviewer type="peer" xml:id="peer_id_here"/>
<report type="peer" resp="#peer_id_here">
<p> I would split the two diagrams that show the the sodium-potassium pump and the
direction of with some text instead of having one immediately after the other. You
could move the action potential diagram down after the part you talk about it in the
text. For the shape diagrams, I'd put them below the text you reference them in,
instead of above. I feel like that would improve the flow of the post. I know you
mentioned you tried to do captions but they didn't work, but I definitely feel like
they could improve the post if you could get them to work (mabye put the captions on
the actual image). If you want, you could also use the captions to reference
diagrams from the text (Example: "As you can see in figure 1, Dopamine will only fit
in the triangle receptor...") For the action potential diagram, I'd use something
that shows the synapse transmitting neurotransmitters, since that is the part that
is crucial in explaining how venom works. I'd throw in an analogy in the paragraph
right after the "basically what's going on?" section to break up some of the biology
jargon. A few typos (just ctrl-F for them): "Neurons contain a long extensions",
"secret" instead of secrete </p>
</report>
<reviewer type="instructor" xml:id="kgs"/>
<report type="instructor" resp="#kgs">
<p>This really is a model project--well researched, well explained, and a quality
example of the genre your group studied. I especially like the way that you handled
the references section, as a conclusion that points readers to further information.
That and the extended analogy you used throughout the post represent some really
creative moves within this generic frame. There were a few moments, especially
before you deployed the shape-fitting analogy for the first time, that I was feeling
a bit out of my depth, so one idea for revision would be to put that analogy at the
outset. That is, instead of explaining the biology and then deploying the analogy,
give us the analogy to hang onto as you proceed through the biology. Obviously I got
through the biology portion and feel like I understand, but I wonder, given the
length, if you might want to more gently lead your reader through the early stages
of your post. Really nice work here!</p>
</report>
</docReview>
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