What Happens in HIV

The topic we are covering for our audio project is a new molecule that will help manage DNA leaving a potential to end retroviruses such as HIV and cancers. Since Nicole and Charlie went over the main paper and what the researchers discovered, I decided I would look a little bit into how HIV affects the Body and DNA. This will give a little bit of background on the subject to help understand what the molecule is helping against.
On the surface membrane of all living cells are complex protein structures called "receptors". A receptor is often compared to a lock into which a specific key or "ligand" will fit. There are at least two receptors on T-lymphocytes to which the human immunodeficiency virus (HIV) sticks. The primary receptor, called "CD4", is shown on the right in the diagram. But a second receptor that loops through the cell membrane 7 times is critical for infection to occur.

HIV infection of a lymphocyte requires attachment of the virus to the cell membrane through both of these "ligand-receptor" links. In cells whose "7-transmembrane receptor" is different, the HIV "key" no longer matches the lymphocyte "lock" and attachment is incomplete. Those cells may avoid infection by HIV.
Tight attachment of the viral particle to receptors on the lymphocyte membrane enables fusion with the cell membrane. The viral contents, including viral RNA then empty into the cell's cytoplasm.

Like other viruses that infect human cells, HIV commandeers the host's machinery to make multiple copies of itself.
An enzyme (protein) that's part of the human immunodefficiency virus reads the sequence of viral RNA nucleic acids that have entered the host cell and transcribes the sequence into a complementary DNA sequence. That enzyme is called "reverse transcriptase" . Without reverse transcriptase, the viral genome couldn't become incorporated into the host cell, and couldn't reproduce.

Reverse transcriptase sometimes makes mistakes reading the RNA sequence. The result is that not all viruses produced in a single infected cell are alike. Instead, they end up with a variety of subtle molecular differences in their surface coat and enzymes. Vaccines, which induce the production of antibodies that recognize and binding to very specific viral surface molecules, are an unlikely player in fighting HIV, because throughout infection, HIV surface molecules are continually changing.
The first major class of drugs found useful in slowing HIV infections are collectively called "reverse transcriptase inhibitors". These include AZT, 3TC, d4T, ddc, and ddl that act by blocking the recoding of viral RNA into DNA. The chameleon-like nature of HIV, however, limits their continued effectiveness.
Once the viral RNA has been reverse-transcribed into a strand of DNA, the DNA can then be integrated (inserted) into the DNA of the lymphocyte. The virus has its own enzyme called "integrase" that facilitates incorporation of the viral DNA into the host cells DNA. The integrated DNA is called a provirus.As long as the lymphocyte is not activated or "turned-on", nothing happens to the viral DNA. But if the lymphocyte is activated, transcription of the viral DNA begins, resulting in the production of multiple copies of viral RNA. This RNA codes for the production of the viral proteins and enzymes (translation) and will also be packaged later as new viruses. There are only 9 genes in the HIV RNA. Those genes have the code necessary to produce structural proteins such as the viral envelope and core plus enzymes like reverse transcriptase, integrase, and a crucial enzyme called a protease.

When viral RNA is translated into a polypeptide sequence, that sequence is assembled in a long chain that includes several individual proteins (reverse transcriptase, protease, integrase). Before these enzymes become functional, they must be cut from the longer polypeptide chain. Viral protease cuts the long chain into its individual enzyme components which then facilitate the production of new viruses.Inhibitors of this viral protease can be used to fight HIV infection. By blocking the ability of the protease to cleave the viral polypeptide into functional enzymes, protease inhibitors interfere with continued infection.

Mutations enable HIV to avoid treatments that involve only one drug, so there is growing use of multiple-drug therapies in which both a protease inhibitor AND a reverse transcript inhibitor are combined.

Finally, viral RNA and associated proteins are packaged and released from the lymphocyte surface, taking with them a swatch of lymphocyte membrane containing viral surface proteins. These proteins will then bind to the receptors on other immune cells facilitating continued infection.

Budding viruses are often exactly like the original particle that initially infected the host. In the case of HIV, however, the resulting viruses exhibit a range of variations which makes treatment difficult.

One step closer in the treatment of HIV

HIV infects more than 33 million people worldwide.  Thanks to current prevention measures, such as certain tests that detect HIV early on and new antiretroviral drugs that can control the virus for decades, the infection with the virus that causes AIDS is no longer a death sentence.  However, use of antiviral drugs for a lifetime raises questions of cost, side effects, drug resistance, and ultimate lifespan.  Current research areas include trying to find a way to flush hidden HIV from cells to changing out a patient’s own immune systems cells, making them resistant to HIV, and then putting the cells back in the patient’s body.  Plus, early human trials of vaccines designed to prevent or treat the infection has since shown to be disappointing.  The greatest challenge for researchers to overcome is the fact that HIV is a provirus that is integrated into the DNA of a host cell, where it has the potential to remain latent or eventually reactivate.  In fact, only one competent provirus in one tissue could reseed the entire infection after a vaccine has been applied.  

HIV Structure

  

The current focus of our audio project is to detail a current study expected to be a revolutionary step in the process of potentially finding a cure for HIV.  Chemists at the University of Texas at Austin have recently published an article titled “A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant” in Nature Chemistry (2011), which detailed the synthesis of a molecule with the ability to tangle itself inside the DNA double helix for an astonishing sixteen days before the DNA liberates itself.  The synthesis of this molecule is an important step in the creation of drugs that can directly go after rogue DNA.  This drug would be revolutionary in the treatment of genetic diseases, cancer, and retroviruses such as HIV.  Specifically, the molecule developed utilizes “electron deficient aromatic intercalating units connected “head-to-tail” by flexible linking chains that slide back and forth through the DNA helix, analogous to how a snake would climb a ladder (according to Dr. Iverson, head researcher on the project).”  Dr. Iverson’s lab is currently examining the relatively long lifetime of this class of molecule when bound to the DNA double helix, as well as examination into the mechanism by which the binding site is recognized among long stretches of unrecognizable DNA.  The researcher’s ultimate goal is to control DNA binding duration and specificity sufficient gene expression in a predictable fashion.       

The original research artricle can be found at Nature Chemistry

Genetics of Michael Jordan, Usain Bolt, and Muhammad Ali

            

                                               Michael Jordan

        Do you think that your childhood and high school experience would have been different if a genetic test had told you that you were predisposed to be an elite athlete? Do you think that your parents would have pressured you or pushed you to play certain sports in hope for a college scholarship or even a chance of playing professionally? There is actually a company called Atlas Sports Genetics that will test a child’s or adolescent’s genetics to determine if they have a gene that they claim plays a role in becoming an elite athlete. Atlas Sports Genetics charges 169 dollars for the test that will tell what type of sports/athletics your child is best suited for. The gene that is being tested for is the ACTN3 gene and it’s R577X variant. If the results show 2 copies of the variant then it means that the child is predisposed to be good at endurance events, 1 copy of the variant means a predisposition for both endurance and sprint/power events, and no copies of the variants for spring/power events. I found this extremely interesting because no matter the results it says that your child has a predisposition to be an elite athlete in some type of event, whether it is a sprinting or endurance events. When in reality, we all cannot and are not obviously elite athletes. In my opinion, I think this is simply to make the customer happy. If you send back results saying that your child is not genetically cut out to be an athlete that isn’t going to make the consumer to happy. On the other hand, if you tell them that their kid is predisposed to be some elite athlete they will tell their friends and they will most likely get their child tested as well.

            Also, I believe that there are some definite moral and ethical issues with this testing. First of all, the idea of a self-fulfilling prophecy. If a child is told they are going to be an elite athlete and then it turns out that they are not, they will be crushed. In addition, this genetic testing completely takes away the environmental factor. It disregards the years and years of hard work and dedication that elite athletes put into their training. Michael Jordan didn’t just walk onto a basketball court one day and was the greatest basketball player ever because of his genetics. He practiced everyday for years and years. Furthermore, Dr. John Mulvihill, a clinical geneticist at Oklahoma University, says that genes don’t completely determine your outcome. Environment and lifestyle must be taken into consideration as well. In addition, Beth Tarini  M.D. at the University of Michigan says that people can have different proteins that make muscles contract faster; that people can have 2 copies of these proteins instead of one which would make them better at sports. However, she states that it is not an absolute prediction, it is just a small predisposition, that work ethic must also be taken into consideration. I think that genetic testing like this is extremely interesting and has some credibility, but must be taken with some skepticism because there are many other factors to take into consideration, more research is needed to completely confirm the validity of these genetic tests. 

Monkey Love

Admit it!  You can't look at two baby monkies hugging without letting out a loud "Awhhh."  I have to admit, the adorable picture is what got me to start reading the article, but I'm glad I did. 

I was also attracted to the article because the title was of interest to me, Whiff of "Love Hormone" Helps Monkies Show a Little Kindness.  I wrote a psychology research proposal dealing with the "love hormone" and its importance to the maintenance of romantic relationships so I am familiar with this special little guy.  For those of you who are not, oxytocin is a mammalian hormone that is released during hugging, touching, or orgasm.  Oxytocin also acts as a neurotransmitter in the brain that is involved in social recognition and bonding, increasing trust and reducing fear, and generosity (PsychCentral).       

So how does one go about making monkies treat each other kindly?  A Duke University research team found that when oxytocin is nasally administered through a children-sized nebulizer the monkies (Rhesus macaques) pay more attention to each other and make decisions to give the other monkey a squirt of fruit juice even if they don't get any.  Two monkies were seated next to each other and trained to select symbols that (1) give a squirt of juice to one's self  (2) give a squirt of juice to the monkey next to them or (3) no juice at all.  Researchers found that when the monkey is given a dose of oxytocin, they were more likely to select the symbol that gave a squirt of fruit juice to the other monkey.  Neuroscientist and director of the Duke Institute for Brain Sciences, Michael Platt, indicated that this study is significant because "it suggests that oxytocin breaks down normal social barriers." 


Not Rhesus macaques, but juice lover nonetheless



These results are great for the monkey population, but what can this mean for humans?  Oxytocin therapy is currently being evaluated as a treatment for autism, schizophrenia, and other disorders that tend to display lack of interest or care for others.  As evidenced by the study, oxytocin has the ability to increase trust and improve social skills.  Research is needed to determine how exactly this process works and if effects are consistent over the long term.  Further, this study shows that monkies are a good behavioral and pharmacological model for understanding oxytocin therapy.

I thought the fact that this study involved monkies was a good hook: it certainly caught my attention.  Also, for me, I was attracted to the title because I've done some past research on the "love hormone."  For those not familiar with it, the name itself is intriguing.  You immediately want to know "what is the love hormone, does everyone have the love hormone, how can I get more in my system, how is this even connected to monkies in the first place?"  For many people, an argument can be made that the "monkey house" is the best exhibit at the zoo because, as humans, we find these intelligent little relatives of ours fascinating and totally adorable.  I tried to grab the reader's attention with the large picture of two baby monkies embracing at the top of my post.  Also, I wanted to make sure I had enough "breaks" or separate paragraphs in the post so it doesn't appear daunting to the reader.  I think this also creates a better flow and the reader's attention is less likely to wander with shorter paragraphs.       

95% mortality rate?

I may be a little weird, nerdy, geeky, or even maybe a combination of all three. I guess I changed my major to the right one, biology, and I love every minute of it. I am in the Emerging Pathogens course here at Ashland where we learn about various infectious diseases that defiantly cannot be seen with the naked eye, and cannot even be seen with many microsopes. However, they can cause some of the most horrific symptoms imaginable and kill you within minutes or days. Some of these symptoms do not even seem real; they seem like something out of a poor Hollywood torture movie. These infectious diseases have cumulatively caused more deaths than all the wars in mankind's history combined. Some of these pathogens have a mortality rate of up to 95%. In my mind, this is hard to fathom. I think to myself basically if I were to get infected with this pathogen I am dead. I may be weird and nerdy to find such an interest in topics like this, but I do. My professor, Dr. Paul Hyman, had recommended a non-fiction novel called "The Hot Zone". He said it was about one of these horrific pathogens called the Ebola virus that can cause fatal hemorrhagic bleeding out of people's eyes and ears. Hemorrhagic bleeding is a 15-30% loss of the total blood volume. This instantly had me hooked. As soon as I got out of class I went back to my room and ordered the book off Amazon. I just received the book today and had started reading, so far it is addicting to say the least. Below is a picture of the tiny virus that can cause the frightful damage.

Ebola Virus

After reading some of the book I decided to look for some information bout the infection and the virus itself. I came across an interesting blog post. Virology Blog. According to this blog post there has been 1850 cases of ebola virus and 1200 deaths since the virus was discovered. This equals a 65% fatality rate. That is scary to think that over half of all the people that get infected with it die. The plague outbreak in the middle ages only had about a 1/3 fatality rate. It is scary to think about what may happen if there were to be an outbreak of a pathogen of this type with a fatality rate about double that of the infamous plague. Due to the extreme danger of this pathogen the Center for Disease Control and Prevention has listed it as biosafety level 4, their highest safety level. This means that researchers that come in contact, or even in the general vicinity of the virus must have full protection suites, masks with their own air supply, rooms in the entrance and exit with multiple showers, and even an ultra-violot room to denature the virus and ensure that it is not brought out of the secure room.  However, I do not want to scare anyone. Ebola virus is an extremely rare pathogen in humans due to the fact that it has not adapted an effective means of transmission into humans. CDC info on Ebola Virus.


An example of a biosafety level 4 suit

Spongebob Was Right?!?!?!

My typical Saturday morning is nothing special; in fact, it’s very comparable to that of most college students (or so I hope). As I woke up at the crack of noon, I stumble to my kitchen grab some Lucky Charms, turn on cartoons, and pull out my laptop for some amusing time wasted on Stumbleupon.com. I was quite content with my childish ways when I saw something on Spongebob Squarepants that just didn’t make sense, Go figure. It’s one of my favorite episodes where Spongebob rips his shorts to make everyone laugh. In it they are on the beach called Goo Lagoon. Wait! Hold It! Alright Spongebob, I’m callin you out… an underwater lake? SHENANIGANS!!! Well as luck would have it my stumbleupon brought me to a site talking about the discovery of, you guessed it, underwater lakes. Dam you Spongebob… So I decided to look a bit more into it and write a blog.

So the most obvious thing here is that the water must be separate in some way, the underwater lake water has to be denser. The water is actually a briney mix of salt water and hydrogen sulfide. Brine is used in reference to the ultra high concentration of salt in the underwater water. It is produced through the movements of large salt deposits called salt tectonics. Since the water is so much more dense than regular sea water, it sinks to the bottom and forms a distinct separation, which acts and flows like a river.

So how do they form? An underwater lake found in the Gulf of Mexico has a suspected history. During the Jurassic period, it is thought the waters in this area were extremely shallow and were eventually cut off from the ocean. The area soon dried out and formed a salt plain. The salt and other materials were thought to be about 8km thick, that’s a lot of salt!!! Overtime the land shifted again and the area was once again exposed to the ocean. The new ultra saline solution sunk to the bottom of the ocean forming the underwater lake. Today, the large amount of salt deposits underneath the water keep a good supply of salt going into the underwater lake.
Hydrogen sulfide is extremely toxic, so it sucks to say that there will probably not be a super fish thriving down there. However, there are always the extremeophiles lurking that just love a great place like this to live. In fact there is an underwater lake on the abyssal plain that has a ton of life in and around it.
So how close are these underwater lakes to actual lakes? The one found in the Gulf of Mexico had banks and plants (that closely resemble trees) growing around it. They also have waves! That’s right, the underwater lake has its own waves! Underwater lakes can have both sandy and rocky shores, which are a focus for all different types of organisms. The waterfront seems to provide a lot of nutrients for life. The “rocky” shore is actually thousands of mussels feeding off the methane from the underwater lake. Fish of all different types hang out because there is a huge abundance of food. A new type of Polychaete has even been discovered.
Ok Spongebob, you may have taken a long way around it, but I actually learned something useful. These underwater lakes are just awesome pieces of nature that are actually big parts in underwater ecosystems. They provide places to live for lots of extremeophiles, and have tons of sea life all around them. There is still plenty of research to be done on them, but they are a really cool discovery. And to think… people say cartoons rot your mind.
ALSO! Check out this video of scientist freaking out about an underwater lake wave!
Reference 1
Reference 2
Reference 3
I have yet to find an actual research paper on underground lakes.

(This is the class assignment part) In this blog I used the hook technique. My opening paragraph is comical and designed to hook the reader into something interesting. It explains the story on how I discovered this topic, and takes a very leisurely way into introducing the topic. It helps the reader realize that the story isn’t going to be filled with a bunch of boring science jargon.

In order to find blogs that interest me I simply went into google and typed in Medical blogs because that is the area of science that interests me the most. After searching for several minutes I came across one called Drugwonks (http://drugwonks.com/). This blogging site appealed to me because I find medications and how they interact in the body fascinating. In addition, I liked this site because they also had some video clips of different scientists talking about drugs and medicine, which looked very interesting. 

Another blog that I found interesting to me was http://www.sciencebasedmedicine.org/. I liked this blogging site because it was at a good educational level for me. Some of the blogs I came across seemed like they were all written by people with doctorate degrees for other people with doctorate degrees and I could not understand them. On the other hand, some were so dumbed down I felt as if I was not getting anything out of reading the blog. This one found a happy medium. It also had an interesting post about Aspirin's risks and benefits.