ThermoXNuclear

Thermo -24; Kenosha, WI -Teh Gurlie =) -AIM contact: Zacharhov -Formerly a Disgruntled Walgreens Photo Tech, now just Disgruntled. -Full-Time Student Extraordinaire [Gateway Technical] -Aspiring Neuroengineer -Metalworking [Bladesmith, Blacksmith, Welder, Machinist] -Warhammer 40,000 gamer [Necrons] - Psychonaut, Transhumanist, Atheist Audio -Power Electronics, Rhythmic Noise, Electro, Dark Ambient, Nordic Metal, PsyTrance, assorted Electronica Genocide Organ, Ka Sol, Grey Wolves, Propergol, 5F_55, Juno Reactor, Turbund Sturmwerk, Hallucinogen, Iszoloscope, Xenonics K-30, Derniere Volonte, Winterkalte, Finntroll, Feindflug, Ah Cama Sotz, Red Harvest I know not with what weapons World War III will be fought, but World War IV will be fought with sticks and stones. -Albert Einstein Horror. Horror has a face... And you must make a friend of horror. Horror and moral terror are your friends. If they are not then they are enemies to be feared. They are truly enemies... -Colonel Walter E. Kurtz

2008-06-06 02:18:03 ET

Ironic how I was all set to make an update at the beginning of June, and just prior to my update, SK burns down. Anyway, glad everything's working again. My summer class hasn't started yet, on account of my teacher being out of the country until the day before the class was supposed to start, and he hasn't even started on his curriculum yet. Not that I'm one to complain about more free time, but now I don't have much to do except sit around and curse at my broken computers (more on that shortly). I don't even have any kind of clue as to what we'll actually be accomplishing in this class so I can't do any learninating on my own. Instead, I've been boning up on my particle physics in anticipation of the LHC coming online later this month (more on that later, too). Earlier this week, in a rare fit of useful productivity, I went and hooked up my brother's computer in an attempt to check out the exact hardware specs. After booting it up, his pirated version of XP Pro prompted me for a password. I called him and after an hour of guessing, he gave up. Great. It's not the end of the world, naturally, but I was hoping to try to recover a copy of my research paper on thermal depolymerization that I wrote on his computer when we lived in Boston. Oh well. It wasn't the best paper I've written but I like to have a copy of all the papers I write, never know when they might come in handy. Case in point: last time I called to my mom, she mentioned having one of her friends over for lunch recently, this woman (forgot her name) was an editor for Cell magazine, a sister publication to the Nature science journal. Anyway, this woman glances over my mom's desk and sees a copy of my latest research paper (the one I posted here). My mom tells her that's my paper, and the woman was impressed with my work. Hellz to the yeah. At least now I know that if none of my research grants get approved, I can still make a small fortune writing intimidating articles for publications to scare aspiring students away from my field. =P So am I just a really big physics nerd or is anyone else fuckin' psyked about the Large Hadron Collider coming online later on in June?? They've already started cooling parts of the apparatus, full operational capacity should be reached later this month with the first particle collision set for sometime in August. In addition to being one of the largest science experiments ever devised, this thing should be able to confirm or deny the existence of the Higgs boson and in the process might necessitate our standard model of particle physics being rewritten. History in the making, I can't wait. Just in case anyone else cares, I'll be keeping tabs on the LHC and its experiments and posting results here. Recently been listening to a lot of Dethklok. It's funny, for a parody band made for a cartoon show, their music is pretty legit deathmetal. DO YOU FOLKS LIKE COFFEE? Alright, enough late-night typing. I'm off to watch a bunch of First 48 episodes I recorded. MA SKers let me know how you're all doing! 9 comments

2008-05-22 16:38:52 ET

Ahh, it's nice to relax for a few weeks before my summer semester. I haven't even had to leave the apartment except to go across the street to buy smokes and when teh gurlie and I go out to eat. I've been keeping myself busy cleaning my shitheap apartment and playing lots of Oblivion. I've also been listening to a lot of Rammstein lately. Techie stuff: My computer has been sliding down the spiral of decreasing stability for some time now, I'm going to do a full wipe and reinstall of XP, but I want to use nLite to customize the install. Does anyone know anything about how to use nLite? I've read a dozen online walkthroughs of how to do it, but it'd be nice to discuss the procedure with a human being too. Online manuals tend to lack the capability to answer pressing questions like "FUCK! FUCK! What the hell's wrong with it now?!" I've also got my brother's computer too. It's faster than mine (2.something gHz compared to my 1 gHz), has more memory, and a bigger HD but no graphics card. I'm thinking about putting the Radeon from my comp into his and seeing if that'd let me run EVE with the snazzy graphics updates. Unfortunately my brother took his brand new computer and promptly subjected it to a horrorshow of shady 3rd party addons, thus filling it to the breaking point with adware and viruses. I don't know if I'm up to the challenge of removing all these, so a wipe is in order for his comp too. However, I noticed in my various reformats of my own computer that random artifacts are preserved through a reinstall of XP. Any chipheads know if there's some way to completely and thoroughly wipe out a HDD before an OS reinstall? Would swiping the physical HDD down with my rare-earth magnet make it totally unusable? Actually, I think I gave my NIB magnet to Brendan before I moved, nevermind. My class, Bioscience Computer Applications, starts June 2. it's an online course so a bunch of my friends from last semester and I are going to get together for a couple weekends and knock out all our projects ASAP so we can spend the rest of the summer slacking off. Also, next spring I will be taking an additional 8 credits in order to graduate with an Associate's in both Bioscience Lab Tech (my current program) as well as Bioscience Manufacturing Tech. The difference between the two programs is two classes, so for a little extra effort I can graduate with two degrees. Bangin'. There's an update, I guess. Life's pretty good here in Wisconsin, except of course, that it's Wisconsin. =P 10 comments

Free! ...for now.    2008-05-14 17:39:19 ET

Finished my spring semester at Gateway. Finally. Didn't get any sleep at all last night, was busy trying to finish my term paper for cell biology. Fucking fiasco that was. Originally planned to write it on the Steps toward Engineered Negligible Senescence program, but stopped when I compared my paper to my outline at 3am and realized I hadn't written past section a. You know, when you make an outline you go like: I. Intro II. Main blah blah thing a. First blah blah talking point blah thing Yeah, THAT a. So I scrapped it and in... *counts on fingers* ...7.5 hours I managed to write a 7-page paper on a related topic that I then printed out 1.5x spaced and 12-point font to yield 12 pages just because I hate trees. Then I took my microbiology final on zero hours of sleep, zero hours of study, 2 packs of cigarettes and 2 32oz cans of Monster. Yup, 32oz, they don't call it the BFC for nothing. So I went in there all psyched to ace it and take off before everyone else like the smug bastard I am and sat there for 2 hours in horror as every scrap of immunology fell right out of my fucking head. Epic fail. Well, maybe not fail, I'm sure I got at least half the questions right and took a bunch of educated guesses. If that nets me my first B in a class at this school I'm going to be pissed. Fuck the immune system. Anyways I'm really fucking tired. Before I go I'm going to post my term paper because it's fucking awesome and I deserve praise and adoration heaped upon me and I'm really fucking tired. Enjoy. **UPDATE: That Micro test I was so worried about? I got a 94?! Maybe I was so sleep-deprived that I hallucinated doing poorly. The 4.0 survives another semester unscathed.** Mitochondrial Mutations as a Contributing Factor in Age-Related Vascular Diseases through Oxidization of Low-Density Lipoproteins, and Engineering Treatments to Reduce Human Mortality Rates Thereof **NOTE: See kids, this is what happens when you name your term papers without the benefit of sleep** Everybody's heard of Low-Density Lipoproteins (LDL) as the "bad" cholesterol in the human body. It's been implicated in numerous malfunctions of the vascular system, but recent research into metabolic functions of human cells may point most of that blame in an unexpected direction: the mitochondria of our cells. Years of seeing various medical research broadcast through the lens of inexpert media outlets has caused most people to cringe in fear at a mention of the word cholesterol (and lately, LDL), but these two molecules are necessary components of human life. Cholesterol is so important in the body, used in everything from digestion to cell membranes, that the body will synthesize and try to maintain a cholesterol level in the body that is largely preset by genetics. If your parents have a genetic predisposition for high cholesterol levels, chances are good that you will have high cholesterol even if you live on a diet of rice and soybeans. LDL provides a necessary function in the body as well, the delivery of that precious cholesterol to cells throughout the body. High-density lipoproteins (HDL) are responsible for gathering up cholesterol and transporting it to the liver, the LDLs carry it out to the cells. In addition, the body uses the ebb and flow of LDLs in the blood as a signaling mechanism, too few LDLs and bodily functions may suffer. LDLs make up around 70% of the total lipoprotein count in our bloodstream, showing just how important this "bad" molecule is. Important though they are, LDLs are a case-in-point example of the axiom, "too much of anything is harmful." But why? Cholesterol is necessary to cellular function; LDLs provide it, HDLs take it away. So why is HDL the "good" stuff? The answer lies not in the lipoproteins nor in the cholesterol alone, but in their interactions with that double edged sword of aerobic respiration: oxygen. To understand why, we must examine aerobic respiration and where it takes place, the mitochondria. Oxygen functions as the final electron acceptor in the end-stage process of aerobic respiration, the Electron Transport Chain (ETC) process occurring inside the mitochondria of almost every cell in the body. Normally, at the end of the electron transport chain the enzyme Cytochrome C Oxidase (also called Complex IV) uses the electrons and hydrogen ions produced by the ETC process to reduce molecular oxygen to water, one of the waste products of respiration. This process can sometimes go awry, however, when the Complex IV enzyme "fumbles" the molecular oxygen, releasing it into the cell before it has accepted its full load of electrons and hydrogen ions. This "fumbling" produces the free radical called superoxide. Superoxide can be incredibly damaging to a cell, capable of reacting with and destroying many important molecules such as enzymes, DNA, and cholesterol. This "fumbling" doesn't happen too often in young mitochondria, but as a mitochondrion ages this happens more and more frequently. As the mitochondrion releases ever-increasing levels of superoxide as it ages, the cell reads this as a signal that the mitochondrion has outlived its usefulness as it is now doing more harm than good. The cell's recycling centers, the lysosomes, now move in and engulf the mitochondrion and break it down. The cell is now short one mitochondrion and so queues another mitochondrion in the cell to divide and produce a fresh, new mitochondrion. Problem solved, or is it? Mitochondria are relics from the dawn of eukaryotic life. They have many features in common with prokaryotes, including ribosome size and a prokaryote-style circular strand of DNA that is independent from the genome of the cell it lives in. This is called mitochondrial DNA (mtDNA), and is housed completely inside the mitochondrion itself. The cell is not capable of reproducing mitochondria; it must induce preexisting mitochondria to replicate. The mitochondrion lacks a nuclear envelope protecting its DNA from damage, and as a result, the superoxide molecules it produces in the ETC have a free shot at the mtDNA. Normally this is not a problem as most mutations or damage cause the mitochondrion to stop working completely, but the trouble arises from the fact that the mtDNA contains the information needed to produce just 13 proteins the mitochondrion needs to keep respiring. This is a very short sequence of DNA compared to the human genome which codes for more than 20,000 proteins. This short sequence drastically increases the likelihood that an encounter with superoxide will damage one of those key proteins, several of which play roles in the ETC process. Knocking out one of those proteins can cause the ETC to shut down but not deactivate the entire mitochondrion. The ETC is the mitochondrion's chief supplier of ATP, the body's energy molecule. Without the ETC pumping out the energy needed by the cell, the mitochondrion's efficiency is greatly reduced, which causes it to try to make up the difference with the preceding, less efficient steps in the metabolic process. We'll get back to that in a minute. For now, it seems that the mutant mitochondrion in question is doomed; it is producing far less ATP than its counterparts in the cell and is sucking up more resources to fuel the less-efficient metabolic precursors to the ETC. However, the ETC is the sole producer of superoxide free radicals in the metabolic process, without the ETC the mitochondrion is producing zero superoxide. This makes the cell "overlook" that particular mitochondrion, instead targeting other aging mitochondria and leaving our mutant alone. Occasionally the mutant will be told by the cell to replicate to replace one of its aging, superoxide-spewing counterparts. Now there are TWO mutants, neither one producing even a single superoxide molecule. Gradually, these mutant mitochondria will completely replace the normal, ETC-utilizing mitochondria in that cell as the cell continues to pass over the mutants for elimination because without any superoxide being produced, these mutants appear to be doing a better job than the normal mitochondria! No superoxide production should be a good thing, right? We'll have to back up one more level in the metabolic process to see how this actually makes things worse. The primary fuel for the ETC process is provided by NADH, which is obtained in the tricarboxylic acid (TCA) or Krebs cycle by the addition of a hydrogen ion to the molecule NAD+. The TCA cycle is the intermediate step between glycolysis (the breaking down of one glucose molecule into two pyruvic acid molecules) and the electron transport chain (using hydrogen ions supplied by NADH to drive oxidative phosphorylation to produce ATP and recycling NADH back into NAD+). In our mutant mitochondrion, the ETC process has been halted by damage to the mtDNA that produces a needed protein. The ETC is responsible for producing the bulk of the organism's ATP (usually around 30 molecules per cycle, depending on the organism), but both glycolysis and the TCA cycle produce it as well, although in far, far smaller amounts (2 molecules each per cycle). With the ETC disabled, the mitochondrion goes into a kind of "TCA cycle overdrive" as it attempts to make up the difference in lost ATP synthesis. Although the TCA cycle does produce ATP, its main product is NADH (8 molecules per cycle), intended to go into the ETC process. NAD+ is another very important molecule, assisting in many other functions besides oxidative phosphorylation. The mutant mitochondrion is now sucking up the cell's free NAD+ at a prodigious rate, converting it into NADH which is only usable in the ETC process, draining the cell's needed reserves. The cell has a built-in safety valve of sorts, called the Plasma Membrane Redox System. In this system, the free-floating extra NADH inside the cell links up with a protein embedded in the cell membrane, which removes the hydrogen ion and converts NADH back into NAD+, shunting the hydrogen ion outside the cell. This increases the concentration of hydrogen ions in the space around the cell, forming a "reductive hotspot." This hotspot becomes a big problem, as the hydrogen ions can react with normal molecular oxygen in the body, forming superoxide free radicals. Many other molecules coming into proximity with the hotspot are capable of forming free radicals as well. Now, instead of being contained within one cell, the free radicals are produced outside the cell and free to move about the body. Free radicals have the power to disrupt or even destroy almost any molecule they bump into, stripping electrons away from organic molecules and altering their charge, causing them to stick to things they shouldn't or warping them into shapes that are unusable or even damaging to other cells (the shape of a molecule is very important to how the body uses it, imagine trying to use a crowbar that's been flattened out or riding a bicycle that is bent in half). As you might expect, having lots of them floating around in your body unhindered can wreak havoc with cells and even whole tissues. As we learned earlier, one molecule that is both very important to the body as well as being omnipresent in the bloodstream is cholesterol. If an LDL molecule is carrying its payload of cholesterol to a cell and bumps into a superoxide molecule along the way, the LDL or its cargo can be damaged, bent into a useless shape, or pick up a charge that can cause damage to anything that interacts with it. Now that we have the pieces in front of us, we can start putting the puzzle together. Mitochondria in cells are damaged by their own harmful byproducts of aerobic respiration. Occasionally, this damage causes mutations in the mtDNA that inactivate the mitochondrion's ETC process. As cells in the body get older, the chance of this type of mutation increases. Tests indicate that different species of animals at the same relative age have correspondingly similar numbers of these mutant, non-ETC mitochondria. The mutants, unable to produce the ATP of their non-mutant comrades, speed up their glycolysis and TCA cycles, producing some ATP and loads of NADH as well. Cells need NAD+ and so convert the surplus of NADH back to NAD+ through the Plasma Membrane Redox System, which ejects the extra hydrogen ions out of the cell. This concentration of ions, called a "reductive hotspot," converts nearby oxygen into superoxide (as well as forming other free radicals). The superoxide is now free to circulate around the body and bloodstream, bumping into and damaging LDLs and their cholesterol cargo. These LDLs continue their mission, acting as Trojan Horses to the cells they supply. These cells ingest the damaged cholesterol and incorporate it into its functions, potentially causing damage to organelles and possibly even the cell DNA. This leaves us with just one more step to take: vascular disease. We have two main diseases in this area, arteriosclerosis and atherosclerosis. These can lead to other problems such as heart attack, stroke, and blood clots. Arteriosclerosis is the gradual hardening of the artery walls, causing loss of elasticity. Atherosclerosis is the localized hardening of an artery wall specifically due to the formation of atheromata (the yellow arterial plaques pictured in heart disease awareness campaigns). Let's add this piece into our puzzle. The arterial walls are composed of endothelial cells, which need cholesterol to function just like every other cell. Our aging bodies produce many of those mutant mitochondria spewing out hydrogen ions and creating lots of free-roaming superoxide molecules and other free radicals. As the LDLs deliver the cholesterol to the endothelium, free radicals damage the cholesterol which becomes incorporated into the endothelial cells. This damaged cholesterol is a different shape than the cell is able to properly use and causes interactions that otherwise would not occur if the cholesterol was undamaged by the free radicals and thus the correct shape. These interactions cause the cell membranes to behave differently, and the overall result is a stiffening of the cell membranes and thus the endothelial tissues. This is the stiffening of arterial walls otherwise known as arteriosclerosis. But what happens if the LDL never makes it to the cell? Free radicals are able to work their way into the spaces and materials between cells, known as the Extracellular Matrix (ECM). Or, if one of our mutant-mitochondria cells is nearby, a cloud of free radicals may be forming right there in the local ECM. At an artery wall, an LDL tries to deliver cholesterol to one of the endothelial cells but gets hit by a superoxide molecule as it passes through the ECM, oxidizing it and causing the LDL to stick in the ECM, unable to deliver its cargo and unable to function properly, bent out of shape by the free radical, sticking to and damaging other LDLs and molecules that pass by. This accumulation continues until the conglomeration is large enough that the tissues of the endothelium treat it as an irritant, and deploy the body’s immune defenses against it. White blood cells arrive on the scene to devour the damaged LDLs, but there’s a problem. As a white blood cell engulfs the oxidized LDL segments and damaged cholesterol cargo, it is deposited into the white blood cell’s "stomach," the lysosome. Lysosomes are vesicles packed with digestive enzymes as well as enzymes that keep the pH inside the lysosomes low enough for the digestive enzymes to do their work. The digestive enzymes work like crowbars, seeking out the weak links in the molecules and breaking those bonds down, dissolving the engulfed particle. But the damaged material is warped, misshapen, and those weak links the enzymes act on may not be in a place where those enzymes can latch onto to break down the molecules. This indigestible material builds up inside the lysosome, accumulating as the white blood cell eats its way through the oxidized LDL, becoming more and more packed with damaged cholesterol and LDL bits. These bloated white blood cells are called "foam cells" as they become larger and larger with indigestible material. The immune response also calls in smooth muscle cells from deeper in the arterial wall. These smooth muscle cells help with the ingestion of the oxidized LDL and damaged cholesterol, becoming foam cells themselves in the process. One by one, the lysosomes of these foam cells can take no more and rupture, filling the cell with the digestive enzymes previously safely contained within the lysosome resulting in the rapid death of the foam cell. The dead foam cells, now leaking digestive enzymes and cellular toxins as they degrade, cause damage to surrounding endothelial cells and further trigger the immune response, recruiting more and more white blood cells and smooth muscle cells to attack the ever-growing accretion of dead foam cells, damaged arterial cells, and oxidized cholesterol. Platelets are dispatched to help repair the growing damage to the artery wall, producing in effect a fatty scab that can obstruct the flow of blood through the artery. These are the classic signs of atherosclerosis. These processes can continue, a slow-motion caking over of the artery slowing blood flow and causing strain on heart muscles and other arteries which may be undergoing arteriosclerosis with age or may be becoming atherosclerotic themselves. In some cases, the fatty scab may break free of the arterial wall completely and begin traveling along the blood vessel. If the scab reaches an organ and blocks off the flow of blood as the vessels narrow, organ failure may result as the blocked organ is no longer receiving oxygen. This can result in cardiac arrest if the scab enters the heart, a stroke if it enters the brain, or pulmonary thrombosis if it enters the lungs. We can see that LDLs and cholesterol are not solely to blame for our vascular diseases; the damaging free radicals present in our blood are the cause of the problem. However, like LDLs, the body often uses free radical formation as a signaling process. Expunging the body entirely of free radicals may result in other problems for the body. Human metabolism is an enormously complex, interconnected system of processes. Like a spider web, poking or moving just one strand of the web may cause the whole thing to collapse or cease to function properly. The usual course of metabolic research takes us in a direction from understanding: understand the problem and where it comes from, and work towards a cure. But like examining subatomic particles, the deeper we look, the more questions we have. Some researchers today are suggesting that in the immediate future, to better protect ourselves against the ravages of age-related conditions (such as the mutant mitochondria and arteriosclerosis), we should begin looking at therapies with an engineering approach. That is, seek out the damage that is caused, stop and/or reverse the damage by treating the underlying cause, and work backwards from a cure towards understanding the specific processes behind the damage. We can apply this thinking to the problem of vascular diseases and their underlying causes. Vascular diseases are caused by the inability of the lysosomes of white blood cells and smooth muscle cells to digest the aggregates of oxidized cholesterol and LDLs that can become embedded in or between the endothelial cells of our arteries and veins. These aggregating materials are obviously not completely indigestible in nature, otherwise ancient grave sites would be littered with not only bones but myriad little tubes of arterial plaque as well. This is not the case, we find no such tubes. The answer lies in soil microorganisms, which can and will digest almost anything if left to their own devices for long enough. Soil microbes ingest food particles in tiny packets that are pulled into the microbe and then merge with the microbe's lysosome. These are the exact same organelles in white blood cells that are unable to break down the exact same material under exactly the same circumstances. This is due to the specialized enzymes in the microbe's lysosome that are not present in the white blood cell's. Not every soil microbe has the necessary enzymes to digest the arterial plaque, but the ones that do hold the key to improving the function of white blood cells in the human body. Projects are already underway to collect soil samples from around the world in an attempt to isolate strains of microbes that carry this plaque-digesting enzyme. Once a suitable strain has been found, gene sequencing can be performed to isolate the specific enzymes in the microbe's lysosome that allow digestion of the plaque. When this enzyme gene sequence is available, it can be transferred into human cells through gene therapy (a process using genetically altered viruses to deliver the gene into human cells, where it becomes incorporated into the human genome). Since not all cells participate in the attack on arterial plaque, it would not be necessary to enact a whole-body therapy; instead treatments of select bone marrow sites could be performed. Bone marrow contains adult stem cells that can differentiate into white blood cells and other immune system cells, giving these cells' lysosomes the ability to properly break down oxidized cholesterol when it is ingested by the immune cell. The result: as oxidized cholesterol and LDLs accumulate in the endothelial tissues of an artery wall and trigger an immune response, the attacking white blood cells consume the offending material as before. But now, instead of engorging themselves with indigestible material and becoming foam cells, their lysosomes break down the oxidized material into its component molecules and when it is all gone, the immune cells disperse and resume their normal activities throughout the body. Atherosclerosis and resulting heart diseases cease to be a major contributor to human mortality (at least in those who undergo the therapy). But we can go one step further. The oxidized molecules that trigger the immune response in the first place are a result of contact with free radicals in the bloodstream or ECM. In turn, the vast majority of these free radicals are a result of the mutant reductive hotspot mitochondria discussed above. These mutants are a result of the mitochondrion's own exposed DNA being bombarded by superoxide free radicals, produced as an inevitable byproduct of oxidative phosphorylation. Tracing the causes of vascular disease even further back in this way allows us to see that another major source of the problem originates with the vulnerability of the mtDNA. Ever since the first mitochondrion became incorporated into the first eukaryotic organism, evolution and natural selection have steadily been working to obviate mtDNA. Of the several hundred proteins needed by a mitochondrion, all but 13 have been incorporated into the human genome. The human genetic code, safely ensconced within its eukaryotic nuclear envelope, is much less susceptible to corruption from free radicals within the cell, and even less so from free radicals outside the cell membrane. The protein genes that have thus far been incorporated into the safety of the human genome are nearly impervious to mutation or damage in comparison to the remaining 13 protein genes still residing inside the mitochondrion itself. The plight of the mtDNA has been likened to living next door to a leaking nuclear power plant. If we could somehow move these remaining thirteen genes into the safety of the "bomb shelter" of the nuclear envelope, mtDNA would become obsolete and far, far less likely to suffer the harmful effects of mitochondrial superoxide byproducts, thus guaranteeing that mutant mitochondria (non-ETC or otherwise) would be an extreme rarity. At first glance, this would appear an easier task than rewiring our white blood cell lysosomes, after all, there's no need for a worldwide hunt for the proper mitochondrial protein genes: they are within each and every one of us! But there is a problem here, and it is the very same problem that has hampered evolution and natural selection encoding those last 13 proteins into the human genome. Every one of those 13 proteins is intensely hydrophobic, or repelled by water. Being hydrophobic inside a cell (which is essentially an all-water environment) causes these proteins to curl up tightly into a ball (remember that a molecule’s shape determines its function). This is not problematic when the protein is produced from the mtDNA which is inside the mitochondrion, so naturally the synthesized protein is already where it needs to be and its shape does not matter. However, with the proteins now being coded outside the mitochondrion they must be imported somehow into the mitochondrion. The mitochondrion already has a system for moving proteins across the mitochondrial membrane consisting of two enzyme bridges called the "Translocase of the Inner Mitochondrial" membrane (TIM) and "Translocase of the Outer Mitochondrial" membrane (TOM), the whole system referred to as the TIM/TOM Complex. The problem arises when the curled-up hydrophobic protein ball must move through the much thinner pores of the TIM/TOM Complex (imagine trying to jam a roll of baling wire down a narrow drainpipe). Not only does the protein not fit, it will try to force its way through, getting stuck in the progress and not allowing any other proteins to pass through the complex. This logjam would cause some serious problems if we were to just yank the protein genes from the mtDNA and drop them into the human genome. Luckily, there are some promising workarounds that have already been experimented with, and even more that are still too complex for us to send to the lab just yet but hold promise nonetheless. Nearly all members of the domain Eukaryota have mitochondria, and thanks to more than a billion years of evolution since their emergence, each organism has slightly different mitochondrial protein structures. The huge variety of eukaryotic organisms we know of today reflect a similarly huge selection of slightly differing protein configurations that function in the same way. Among the configurations we have studied, some species have protein configurations that are less hydrophobic that ours. Less hydrophobicity means that the protein does not curl into such a tight ball in an aqueous environment, meaning that with some extra effort, the TIM/TOM Complex can successfully import the proteins into the mitochondrion. The extra effort comes in the form of a targeting sequence, a specially-constructed "nose cone" that directs the protein to enter the TIM/TOM Complex in a certain orientation that allows it to pass through, after which a special enzyme shears off the targeting sequence and the protein is ready for action. This operation has been successfully performed at the Department of Neurology at Columbia, taking a less-hydrophobic mitochondrial protein gene isolated from a species of algae and inserting it into an isolated human cell especially cultured to produce the mutant non-ETC mitochondria discussed earlier. The results: the human cell imported the gene and produced the protein, which successfully passed through the TIM/TOM Complex and restored the mitochondrion to pre-mutation ATP production rates (effectively reversing the mutation). This success is very promising, but the gene imported codes for just one of those 13 hydrophobic proteins. Finding the remaining 12 proteins in less hydrophobic configurations existing naturally in other species would be incredibly lucky but would in all likelihood take a long time to sift through so many eukaryotes. In the interest of time, researchers would most likely elect to study a few such similar proteins and then modify these existing proteins to function as the remaining proteins. Another possible solution that is still in the theoretical stage involves the use of inteins. Inteins are segments of proteins that are able to excise themselves and rejoin the remaining segments (called exteins) with a peptide bond, essentially remodeling the protein to a specific shape for a specific purpose, and then changing the shape back. Intein functions are not well understood, but the basic concept is a little like the ambitious college prank of disassembling the dean’s car, carting each individual piece inside, and then reassembling the car in his office. This is not an entirely accurate metaphor as the exteins are never actually separated at any point, but the important visualization is that of changing the shape of a structure to fit it through some sort of opening, then changing the shape back. Researchers are working on ways to insert inteins into strategic places on the hydrophobic proteins, allowing the proteins to reform into a shape that can pass more easily through the TIM/TOM Complex. Again, this method is only in the theoretical stages of development, it is likely that we will not possess the understanding necessary to perform this sort of procedure for some time. Once we have a safe and foolproof way to get the mitochondrial proteins into the mitochondria where they can function, the actual transfer of these protein genes into the human genome is relatively simple using gene therapy (the same procedure discussed for the lysosomal enzymes). This ‘bomb shelter’ method of keeping mitochondria relatively mutation-free, although much more elaborate and involved than modifying the lysosomal enzymes of immune cells, offers a powerful weapon against age-related pathologies as well as vascular diseases. Cutting right to the root source of the problem (excessive free radicals in the body), oxidative stress throughout the body could be marginalized, significantly reducing free radical damage to all tissues in the body, not just vascular tissue. These two methods of preventing oxidative stress, white blood cell lysosomal enzyme modification and mitochondrial mutation prevention, when taken together could change our perceptions of a "typical" human lifespan. There are many more strategies for helping us live longer, but the combination of having less oxidative stress to damage tissues and molecules, and the ability to consume and break down previously indigestible accumulations of substances deal with the two recognized greatest threats to human health and well-being (cell/tissue stress and accumulation of indigestible material in and around cells). The implications of achieving a longer lifespan with a greater number of healthy, active years are enormous. Some current biogerontologists are hopeful that the first line of anti-aging therapies will become available in the next 30 years. We are fast approaching a time when we can control with ever-finer precision the course of human evolution. Sources and Further Information: Methuselah Foundation: Steps toward Engineered Negligible Senescence (SENS) Program http://www.mfoundation.org/sens Methuselah Foundation: LysoSENS http://www.mfoundation.org/index.php?pagename=lysosens Methuselah Foundation: MitoSENS http://www.mfoundation.org/index.php?pagename=mitosens Wikipedia: Mitochondrion http://en.wikipedia.org/wiki/Mitochondrion Wikipedia: Lysosome http://en.wikipedia.org/wiki/Lysosome Wikipedia: Oxidative Stress http://en.wikipedia.org/wiki/Oxidative_stress Wikipedia: Metabolism http://en.wikipedia.org/wiki/Metabolism Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetimes By Dr. Aubrey de Grey and Michael Rae St. Martin’s Press; 2007 @ Amazon.com **NOTE: Yeah I cut it off pretty abruptly, I was finishing this in the class period it was due** 23 comments

Err...    2008-03-12 01:23:14 ET

Wow... Um, yeah, Subkultures... Oops? Christ, it's been so long since I updated here I wonder if anyone cares anymore. No matter, regurgitating one's unsolicited thoughts and opinions into the soulless void of electronic space is a time-honored tradition and I intend to continue it. =P So where to begin... - My lease in Brighton, MA was up in July, I think, of 07, so once again I packed my worldly possessions into boxes and moved again out to the midwest. Kriz and I got an apartment in Kenosha, Wisconsin (yes, Wisconsin, for cryin' out loud) that is comparable in space to my apartment back in Boston but for 1/3 the price. Not too shabby! Now I just need to get my hands on a camera to take pictures of some of the truly ridiculous signs on churches around here. Take, for example: "Looking for a sign from God? Well here it is." - I started school here at Gateway Technical College which is only about 2 miles away from me. I can walk there when it's not snowing like a motherfucker. I'm currently about halfway through my Bioscience Laboratory Technician associate's degree. - I don't have any sort of real job for now, I'm living on my student loans and occasional handouts from my parents, Kriz has magnanimously undertaken the responsibilities of bill paying and grocery shopping while I focus on school. This has worked out well, although we are tight on money at times. Last semester I pulled a 4.0 GPA and made the Dean's List though, so there is much to be said for unfettered study time. I've also been able to make a spot of money here and there tutoring classmates in the arcane arts of chemistry and microbiology. Things are pretty good right now. I'm having fun in school (it IS possible after all!), Kriz and I are doing well, and I'm reasonably content with my life right now, except for the whole "being 1000 miles away from best friends and family" thing. I do miss my friends and family, but over giftmas break I flew back home and there was much drunken carousing. I felt all weird and grown up, flying home from my life elsewhere to see my family again. Gah. Looking over my most recent updates ("recent" doesn't seem like the right word, but I'll go with it), guess I should follow some stuff up. 1) Still smoking. Oh well. Trying quitting again soon, but I need the chemical stimulation to get up for my morning classes. 2) My incredible performance on the GED, which I was assured would pave my college path with vast riches and scholarships, has so far amassed me Jack and Shit. Doesn't matter too much, I guess. 4.0 GPAs arent exactly easy to pull off in Biotech programs, so if I keep it up I'm sure someone will take notice of me eventually. 3) My cat, the one who I thought I would have to put down, is still living in Boston with my brother. He's quite the old fart now, but still alive and well. It's been almost 2 years since the vet told me he could die any day now, and he's still kickin' it. I miss him, but I know he's happy and doing okay. 4) I'm still poor. 5) I am also still playing EVE. Well, that's about all I can squeeze out of my brain as far as an update goes. Seeing as how I've broken the million years or so of lack of SK postings, and now that I have free time on my hands every so often, I suppose I could mention something about updating more often. But in the past that hasn't ever panned out, so instead I'll just say that yes, I am still alive, and it'd be nice to reestablish contact with all my old friends on Subkultures. Well, I have an early morning tomorrow with Cell Biology and Microbiology, so I must be off. I leave you with various ways to contact me, in the hopes that at least some of you will! -AIM: Zacharhov -EVE: Kommisar Volkov -XBox Live: Soldier Volkov 5 comments

Pestilent    2007-04-25 05:18:38 ET

*Wheeze, splutter, cough, sniff, hack, sweat, snooze, overheat, wheeze, ache, cough, sniffle, hack, hack, sweat, cough, ache, die* Why yes, I have the flu. Thought I'd made it all the way through this winter without it, and yet here it is, after a week of amazing weather and now I'm stuck inside hacking my guts out and wrapped in a blanket with the chills despite my thermostat not having moved from 85 for the past several months. Been trying to sleep for hours, can't. Too warm, too cold, all that usual flu nonsense. Guess I'll make myself some more Theraflu tea (WAY too expensive for tasting like crap, IM-not-so-HO) and check my EVE account, again. Maybe I'll have another one of my spectacularly deranged fever dreams later. Always something to look forward too... 4 comments

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