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New Blog August 2, 2008

Posted by Hegemony in Uncategorized.
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I’ve decided to deversify.  I often find that the science I want to blog about wouldn’t be of interest to many people.  When I find something to write about here, it has often been a while since the last post.  So, please visit my new blog “Honestly Anomalous“.  I’ll still be blogging about science, but also about sci-fi, technology, and whatever happens to make me chuckle.  I go by Oolon Colluphid there, so don’t get confused.

So… What’s An Antibody? May 7, 2008

Posted by Hegemony in Science.
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Wow… has it really been this long since I posted? Sorry ’bout that. Life and such.

Antibodies are really some of the most interesting proteins you have. Their use and production are both absolutely remarkable and you owe it to yourself to at least appreciate their existence.

Congratulations, if you’re reading this you’re probably a vertebrate (if not, please do contact me at once, I’ll have some questions). As a vertebrate you have billions of antibodies floating around in your blood stream and tissues. When antibody producing cells are maturing, those that have antibodies that recognize your own cells as foreign are destroyed. You only want antibodies that will “tag” stuff that isn’t part of you. To put it simply an antibody allows for specific clearance of threats. They are what your body uses to recognize what’s “self” and what isn’t. So how does it do that? Well, lets have a visual…
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Yeah… I got it from wikipedia. Creative commons and such. The antigen binding site is where all the action happens. Each antibody has a specific pattern of amino acids in that region that give it the ability to bind to a specific foreign particle (an antigen). Each antibody works for only one antigen (hence the little carved out shapes in the diagram… it doesn’t actually look like that). You have antibodies with antigen binding sites that correspond to almost any bacteria or virus that you could encounter. Having antibodies sticking to something is like yelling to you immune system, “Holy crap! This shouldn’t be here!”.

The opposite end of the antibody (the blue bit) is always the same throughout a species. This corresponds to various receptors that allow the foreign junk that it’s stuck to to be dealt with. When antibodies bind foreign things and then use their species specific portion to attach to certain cells it can start a cascade of reactions that activate a stronger immune response. This is basically what a vaccination is doing. It introduces an antigen that causes a strong immune response. This effectively immunizes you against an infectious agent.

Ok… so the cool thing: since each antibody only has high binding affinity for a single antigen you need a lot of antibodies, each with a different variable region. You need to cover all the possible nasty bacteria and viruses you might encounter. Since that variable region is produced from the DNA used to make the protein you’d expect that a huge number of genes would be required, right? Well there aren’t! Because the cells that make antibodies (B-cells) can actually change their DNA. This sort of mutation happens only in the immune system. I won’t trouble you with the specifics, but the DNA for the variable region is randomly altered. Each B-cell does this once and this is what determines what antibody this cell makes for it’s entire life span. So with only a little DNA your cells can make all the different antibodies you need. Neat, huh?

Public Understanding of Science September 28, 2007

Posted by Hegemony in Science, Science Rants.
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Science is important… really important. But the average person doesn’t really pay much attention to it. Some may find it intimidating, others boring, still others are opposed to scientific reason preferring to place their confidence in spirituality. People avoid scientific news and information too often. This may not seem like a problem on its surface. But I am here to tell you that it is (at least in my opinion). Fact of the matter is that people make poor decisions based on bad science. If they have no frame of reference how can they be expected to know good science from bad? If we are to survive as a species we need to embrace science.

Don’t believe me? I see you sitting there, smirking… well wipe that grin off you face. For I come armed with proof. Case in point, the dihydrogen monoxide fiasco. “But wait”, you’re saying, “wasn’t that like 15 years ago?” Yes… yes it was. But people still fall for it. Otherwise reasonable people that don’t have a good grasp of science (or internet access apparently) publicly state they are against dihydrogen monoxide. Just look at the wikipedia page here. But that’s a mostly harmless example… you can’t go far saying things about wanting to ban water before someone sets you straight. But sometimes there are those that take it one step further.

Next we have good old intelligent design. People that are unable to come to grips with a more adult way of viewing life and the world become creationists. Those that wish to trick the ignorant into believing what they do call it “intelligent design”. Ignorance of science makes people susceptible to this. There have been places and times when this has gained so much support that school boards have attempted to have intelligent design taught in biology courses. See examples from recent years here and here. The second is about the evolution disclaimer stickers from Georgia, I won’t get into that too much here. This is a threat to education. If you give children mixed messages about science they may never trust what it really has to teach them. Of course this just causes more people to be ignorant of science.

Now we see the culmination of what can happen when people do not understand science. A new rise in HIV infection seems to be linked to a misconception among young people that there is a cure for HIV. Read about it here. From the article:

The poll of 1,000 people found more than 20% of people aged 18 to 24 mistakenly thought there was a cure for HIV.”

Wow, how about that… just because science isn’t your thing isn’t any reason to assume anything about dangerous diseases. What a rude awakening that would be to go into the doctor and find out you have HIV and then ask about the cure. No one should be left in that situation. No one should be failed by society like that. Science should be presented as a necessity to one’s understanding of the world. We should all work toward that.

What are Proteins and Where Do We Get Them? June 19, 2007

Posted by Hegemony in Science.
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I’ve said it before and I’ll say it again. We are protein based beings. Everything we do on a molecular level relies on a protein (note, an enzyme is a protein) in some way. I think a lot of people just don’t understand what that means. It all comes back to the Central Dogma. It’s a memorable term coined by Francis Crick (the co-discoverer of DNA along with James Watson) in 1958. It is basically the name given to the process by which genetic information is utilized. This is one of the most important concepts in biology. But it is not static as the term dogma would suggest, a fact often lamented by Francis Crick. We are finding new components of the central dogma even still. This is frankly, spectacular.

There are several main components of the central dogma. Firstly, DNA is a storage mechanism and is copied as cells divide. This is mediated by the enzyme DNA polymerase (in humans). When DNA is read by RNA polymerase (often triggered by an external stimulus) a strand of RNA is produced. RNA is much the same as DNA but in humans it is a single strand as opposed to the DNA’s double helix. This is called mRNA and the process by which it is made is called transcription. mRNA is exported to the cytosol from the nucleus and attaches to a ribosome. The ribosome reads the mRNA three bases at a time (this is called a codon). Each codon corresponds to a particular amino acid. Thus, the RNA is used to produce a chain of amino acids called a polypeptide. This then folds to attain its functional conformation (or shape) either by itself or with the help of chaperone proteins (a subject for a different article). This happens because the pattern of amino acids have different affinities to water, charges, and shapes. And that’s where you get your proteins.

But that’s not all there is to the central dogma. That’s what makes it interesting. In viruses we see an interesting variety of changes to the dogma. Many viruses store their genetic information as RNA instead of DNA. They may use RNA polymerases to replicate their genetic material. So here we see RNA producing RNA instead of DNA producing RNA as in humans. Some RNA viruses also use reverse transcription to change their RNA genome into DNA as a method of infecting cells.

Even now we are discovering new aspects of the central dogma that may apply to humans. New frontiers are opening up before us. Recent research indicates that some genes may be copied several times, and that the copy number may affect gene expression and thus, proteins. There is also the possibility that methylation plays a role in gene expression. This theory is called epigenetics, and basically says that changes in the physical structure of the DNA chain (caused by methylation) can alter expression. This structural change could even be inheritable… pretty cool. I hope this (long) post cleared up what proteins are and where we get them from.

Life, the Universe, and Everything. May 31, 2007

Posted by Hegemony in Science.
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Life is a funny thing. The complexity of it all can be staggering at times. Some people either cannot or will not look past that complexity to the natural laws underlying it. It must be hard for them to imagine the possibility of life outside of our planet. These are the creationists and intelligent design advocates (though I think they should drop the pretense and admit those are one in the same). Evolution is driven by environmental pressures, it’s not some process that happens magically on its own. It’s not random, though the natural selection that drives it can be random. The concept itself is not that difficult to grasp but many people never hear the facts.

I’m not saying that we as scientists have all the answers to how life began. But we have a fair idea backed by the basic laws of science. We know that enzymatic activity is the basis of life. You, me, every living thing on this planet is protein based. We know that amino acids are the building blocks of proteins, and these compounds exist independently of life. Every amino bond finds it’s most stable conformation by sampling different bonding angles millions of times per second. Thus, biomolecules can self-assemble. More possibilities arise with the discovery of ribozymes. A ribozyme is a piece of RNA that has catalytic activity like a protenacious enzyme. Early life was almost certainly RNA based. The increased mutation rate (it’s an order of magnitude larger than DNA) would have caused evolution to take place at a relatively astounding rate.

Bare with me as I wax philosophical. It’s downright arrogant to entertain the idea that this planet was created the way it is with a whole empty universe around it. Understanding evolutionary principals opens up a whole world of uplifting thoughts. What if the universe is teeming with life? What if they would like to meet us? I’d like to think that it is, and they do. Hell, I’m relatively certain on the first count. But maybe ET knows about us and finds us rather distasteful. The small blue planet run by psychotic apes we are.

Recent extra solar spectrographic studies have shown organic molecules exist outside of our solar system. We are constantly finding new extra-solar planets as our detection methods get more sensitive. There are hundreds of billions of galaxies, each with a few hundred-thousand up to (and more commonly) hundreds of billions of stars. There could be an unfathomable amount of life in the universe. It would be nice if we could avoid blowing each other up long enough to meet some of it… even if it doesn’t like us so much.

The WHO agrees, circumcision reduces HIV infection March 28, 2007

Posted by Hegemony in Health, Science Rants.
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My apologies for the lack of updates as of late. This post will be part science and part crazy tirade so bear with me. Be aware, parts of this may be a little graphic.
The World Health Organization has just announced that they will begin plans to increase the availability of circumcision to Africans. This comes after three studies have shown that circumcision reduces the risk of contracting HIV for heterosexual men by at least half. That is downright significant. As it turns out, the foreskin is filled with a particular dendritic cell (a Langerhans cell) that HIV tends to infect upon being passed on.

So what is HIV? HIV is a virus, a retrovirus to be exact. It stores its genetic information as RNA and uses a viral protein called reverse transcriptase to make its RNA into DNA upon infecting a cell. The virus incorperates itself into the host cell’s genome. It multiplies when the host cell becomes activated and initiates its transcription factors. HIV can infect several types of immune cells but is particularly fond of helper T-cells which is where the majority of the damage is done. With no helper T-cells there is nothing to direct the immune response.

There have not yet been any studies on the effectiveness of circumcision on homosexual transmission but it can be assumed to a certain degree that it is beneficial. The WHO also recommends increased oversight of the procedures so that men know all the facts before undergoing the operation. Counseling would also be used to ensure these men do not become over-confident. This is solid science now people, no use arguing about it if you just don’t like the idea of circumcision. Which leads me to the crazy tirade… [clears e-throat]

Why in the holy crap do I hear so many people comparing circumcision to “female circumcision”? That’s really just a nice way of saying female genital mutilation (FGM). It’s just not the same thing; removing some external skin is not the same as FGM. It’s like they feel this gives some credence to their objections to compare it to a horrifying practice like female genital mutilation.

As far as I’m aware, a circumcised penis works pretty much the same. A victim of FGM on the other hand… has often had their clitoris removed, labia cut down, and the entire area slashed to promote the growth of scar tissue. This leaves a woman unable to become aroused and makes sex a painful, unpleasant experience. In what way does that sound like a simple male circumcision? Does that really sound like a reasonable comparison? I applaud this move by the WHO and can only hope that it helps us get ahead of the AIDS epidemic. I invite polite disagreement with me but abusive or obscene comments will be removed.

Why Don’t Infants Shiver? January 27, 2007

Posted by Hegemony in Health, Science.
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In a recent post I talked about a metabolic poison that can decouple electron transport and oxidative phosphorylation.  You may be interested to know that this process is a known mechanism in infants.  This is not mediated by the same metabolic poison as I mentioned before, but rather by a naturally produced protein called thermogenin.  This protein causes the uncoupling of electron transport and oxidative phosphorylation in a cell’s mitochondria.  Check back a few posts for the mechanism if you’re interested.

So where does this take place?  If it took place in all cells (like if someone were to take that metabolic poison) the infant would be unable to survive.  Infants have specialized cells called brown adipose tissue or “brown fat” where this takes place.  These cells have many small fat vacuoles and mitochondria.  The normal fat found in adults is referred to as white fat.  Adults don’t have much (if any) brown fat.  By decoupling electron transport and oxidative phosphorylation the cell redirects the metabolic energy.  This results in the generation of heat and infants don’t need to shiver.  Neat, huh?

How Dengue Tricks the Immune System January 14, 2007

Posted by Hegemony in Health, Science.
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Dengue is a medically relevant virus that is common in tropical climates. The virus itself is a single stranded RNA virus. It is spread by the mosquito Aedes aegypti. It causes two diseases, dengue fever and dengue hemorrhagic fever. One cannot contract the second without having had the first. This is a very interesting component of dengue infection that relies on the host’s immune response. It is also why vaccination for dengue is seen as a risky proposition.

There are four different strains of dengue virus. These strains are very similar; so similar in fact that the immune system recognizes all of them after seeing only one. But recognition is not protection. Human T-cells each are programmed to recognize a specific pattern (or antigen). In the first infection virus particles will be captured and processed by so-called antigen presenting cells. These viruses will be presented to T-cells causing them to become activated. And likewise B-cells will encounter their antigen free floating and become activated. B-cells produce antibodies. Antibodies are used (among other things) to tag the viruses to encourage their uptake by macrophages (called opsonization) and inactivate them.

This first infection is known as dengue fever and will last 6 or 7 days. Its symptoms are much like a severe flu. Most people get over it without incident. If one becomes infected again things could go wrong. There are four strains of Dengue, all of which are all very similar. If you are infected with a different strain than you encountered the first time, you will contract dengue hemorrhagic fever.

But why does this happen? As it turns out, the antibodies from the first infection will attach to the virus particles but will not inactivate them. The strains are just different enough to remain active in the presence of another strain’s antibodies. These are referred to as “non-neutralizing antibodies”. These antibodies will still cause opsonization. So Macrophages willingly take up infectious viruses. This accelerates the course on infection to such a degree that hemorrhagic symptoms are seen. It’s one of those interesting times when our immune systems fail us. Imagine if people were vaccinated for dengue. What if someone missed one of the four vaccines or one was innactivated by improper storage? They would be quite prone to dengue hemorrhagic fever.

Bad Idea: Metabolic Poison as a Weight Loss Drug December 9, 2006

Posted by Hegemony in Health, Science.
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In case you’re confused I have changed the title of this article. The old title was attracting search engine hits from the wrong crowd. Not only were these searches disconcerting, these people were spamming my blog.

There is a fad out there right now. Some very body conscious people are using a substance, that for all intents and purposes, is a poison. You may wonder why they would do this. Because they can loose weight with it. We’ll call this DN (as I don’t want to give any impressionable people any ideas) and it is categorized as a highly toxic metabolic poison. Users of it know what I’m referring to. The mechanism by which it operates is downright interesting, and the consequences of it’s use are just as frightening.

Here’s a little background… DN was originally used in the 1930’s as a diet aid. It was one of those instances where people thought they had stumbled upon a miracle drug. People lost weight and everything was all well and good. Until they began to realize even a small overdose could cause a fever so high that it resulted in death. Not to mention the longterm effects include such favorites as cataracts. It fell out of use in the late 30’s and it stayed that way until the 90’s. Having apparently forgotten the lessons learned the first time around people began using it again. It is still popular with bodybuilders, models, athletes, and even some people with eating disorders. But how does it work, and what makes it so dangerous?

To answer that we’ll need a quick review of biochemistry. In our cells we have many proteins called enzymes. Enzymes are used to catalyze reactions that would not proceed on their own. Almost every reaction on the molecular level involves an enzyme in some way. Many of these enzymes are powered by that all important molecule, ATP. When an enzyme binds and hydrolyzes (breaks apart) ATP it allows the enzyme to undergo a conformational change (change shape). So we can think of ATP as imparting energy to the enzyme. This allows the enzyme to preform it’s specific reaction.

You need lots of ATP and most of it is produced in the mitochondria of your cells. These are small membrane bound structures that are probably the descendants of engulfed bacteria (but that’s another story). I won’t get into the intricacies here but this process relies on a series on enzymes that transport protons into a space between the mitochondria’s two membranes (known as the electron transport chain). This “proton gradient” leaks back out through another enzyme called ATP synthase. As the protons pass through the channel of the enzyme they initiate a conformational change that allows ATP synthase to make ATP. This is called oxidative phosphorylation.

Now, when you eat food the sugars eventually result in the production of ATP which allows your cells to synthesize complex molecules like fatty acids (among other things). If all you care about is loosing weight you can turn the production of ATP off and you body will begin breaking down fat for energy. This is called decoupling oxidative phosphorylation and it’s what DN does. It is capable of passing back and forth between the mitochondria’s membranes. It picks up protons from the gradient and releases them when it passes back to the other side, effectively undoing the work of the electron transport chain.

The problem with this is that that energy has to go somewhere instead of to ATP. It gets released as heat. Lots of heat. So much in fact, that even a small overdose causes core body temperature to rise above 104F. This is absolutely deadly. Proteins denature from the heat.

But still people use this stuff for quick results. It’s just not worth the risk here people. If you have body image problems seek professional help and don’t resort to these quick fix gimicks. You never know how dangerous it could be. Before trying ANY weight loss plan, consult a doctor. But just lay off the pills… they can be dangerous, as I’ve outlined above. And to those that use it professionally for that little extra edge (in athletics or bodybuilding), you are idiots. If anyone is interested in the identity of this substance, drop me a line. I’ll let it slip so long as you have a legitimate reason for asking.

How do prions work? November 21, 2006

Posted by Hegemony in Health, Science.
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Prion diseases operate differently than any other class of disease we are currently aware of. It is reliant on mutated forms of a common mammalian protein known as prion protein (PrPc). PrPc is highly homologous among mammals. In humans this protein is expressed in the central nervous system as well as in leukocytes and the gut. Common diseases known to be prion in nature include kuru, scrapie, Creutzfeldt–Jacob disease (CJD), Bovine Spongiform Encephalopathy (BSE/”mad cow”), and Gerstmann Straussler Scheinker (GSS) disease. Prion diseases are unique also in that there are three known ways for one to contract them: infectious, inherited, and sporadic.

A modified prion protein (PrPsc) has properties very different from those of the unmodified PrPc. PrPsc is highly resistant to the enzymatic degradation of the ubiquitin-proteasome system causing them to build up. This is a result of the changes in the secondary structure of PrPc, that is PrPsc has many areas of alpha helixes converted to beta sheets. These proteins build up in the brain causing cell death.

When a PrPsc molecule in introduced into a healthy animal it causes conformational changes in the healthy PrPc forms of the protein. This process is known as “Pruisner’s Theory”. This theory is evidenced by the tendency of aggregates to resemble the primary structure of the PrPc of a particular organism.

Recent studies have hinted that PrPsc aggregates are not necessary for prion-related neurotoxicity. If proteins are non-functional they are tagged by ubiquitin and degraded in a proteasome. This goes for PrPc as well. It has been discovered that if the ubiquitin-proteasome is inhibited, misfolded PrPc will build up in the cytosol and cause classic prion-related neurotoxicity. These PrPc proteins will aggregate in the cytosol and cannot be cleared by reinitializing the ubiquitin-proteasome system.

There are several findings in mouse studies that must be taken into consideration when thinking about the role of PrPsc in disease. It cannot cause disease when no PrPc is present. In a study mice with out the PrP gene (prpn) the PrPsc was unable to cause disease. Mice with truncated prpn producing non-functional PrP have high levels of cytosolic PrP and have massive neuronal loss. Older mice can spontaneously develop these symptoms, presumably sporadically. If PrPc production is inhibited in early PrPsc infection symptoms will not develop. The concentration of PrPsc does not seem to have an effect on the severity of the disease.

The new research raises many questions about the role of PrPc in relation to PrPsc exposure. It seems clear that PrPsc converts PrPc to the highly toxic form. However, it also seems clear that PrP itself can contribute to disease if the ubiquitin-proteasome system is not working properly.

It is put forth by researchers that the introduction of PrPsc may not be the determining factor in the development of neurodegenerative symptoms. This could be caused by a defect in the processing or metabolism of PrPc, or in the prpn gene itself. They state that an exogeneous form of PrPsc may initiate the events leading to the build up of PrPc in the cytosol and that this PrPc may fuel the further accumulation of PrPsc aggregates. This process may actually explain infectious, inherited, and sporadic prion disorders.